Here you will learn all about Hydrogen Water and how it has been shown to benefit the body.
The Role of Inflammation in the Pathology of Acne
Oxidative stress in acne vulgaris: an important therapeutic targetAddressing Free Radical Oxidationin Acne Vulgari
Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injuryHydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injuryHydrogen-rich water protects against acetaminophen-induced hepatotoxicity in miceHydrogen-rich water protects against acetaminophen-induced hepatotoxicity in miceHydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injuryHydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injuryHydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injuryInjuryHydrogen–water enhances5-fluorouracil-induced inhibition ofcolon cancerHydrogen–water enhances5-fluorouracil-induced inhibition ofcolon cancerHydrogen–water enhances5-fluorouracil-induced inhibition ofcolon cancerTop of Form
ABSTRACT
The conventional perspective of acne pathogenesis holds that Propionibacterium acnes colonizes the duct of the sebaceous follicle, causing an innate immune response and the progression from a so-called noninflammatory comedo to an inflammatory papule, pustule, or nodule.
However, this viewpoint has come under increasing scrutiny over the last decade, as evidence has emerged supporting a role for inflammation at all stages of acne lesion development, perhaps subclinically even before comedo formation. The immunochemical pathways underlying the initiation and propagation of the inflammation in acne are complex and still being elucidated, but may involve Propionibacterium acnes as well as several inflammatory mediators and their target receptors, including cytokines, defensins, peptidases, sebum lipids, and neuropeptides.
This review presents evidence to support the notion that acne is primarily an inflammatory disease, challenging the current nomenclature of noninflammatory versus inflammatory acne lesions and suggesting that the nomenclature is outdated and incorrect. The evidence in support of acne as an inflammatory disease also has clinical implications, in that anti-inflammatory drugs used to treat the disease can be expected to exert effects against all lesion stages, albeit via distinct mechanisms of anti-inflammation.
References-https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3780801/
Oxidative stress in acne vulgaris: an important therapeutic target Addressing Free Radical Oxidation in Acne Vulgari Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in mice Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in mice Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury
Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord Injury Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancer Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancer Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancer Top of Form
Oxidative stress in acne vulgaris: an important therapeutic target
ABSTRACT
Objective: There has been an increasing focus on the extent to which oxidative stress is involved in the pathophysiology of acne. The aim of this study is to investigate the existence of oxidative stress and inflammatory marker IL-8 in patients with acne vulgaris, and the role of oxidative stress as a therapeutic target in the treatment of acne vulgaris.
Methods: A randomized prospective clinical trial was carried out on 56 patients of both sexes with age range of 14-35 years who attend to outpatient clinic in Al-Hussein Teaching Hospital-Kerbalaa -Iraq over a period from December 2011 to May 2012, all patients examined clinically by dermatologist and classified according to disease severity. Serum levels of glutathione (GSH), malondialdehyde (MDA) and interleukine -8 (IL-8) in the acne patients were measured by using ready- for- use Elisa kits, and compared to that of 28 healthy volunteers. Results: The results of the serum level analysis of MDA for the acne patients (expressed as the mean± standard deviation) was highly significant (P value ≤ 0.001) higher than that of healthy volunteers, while serum level of GSH was highly significant (P value ≤ 0.001) lower in acne patients compared to healthy volunteers; there is a significant difference (P value ≤ 0.05) found in serum levels of IL-8 between the acne patients and the healthy volunteers.
Conclusions: The results obtained in this study clearly showed the existence of oxidative stress in patients with acne vulgaris, and that oxidative stress along with inflammation play a critical role in acne pathogenesis; furthermore, oxidative stress in acne patients may represents a potential therapeutic target and interference with antioxidant is a rationale choice.
References-https://www.ejmanager.com/mnstemps/66/66-1345206572.pdf
Oxidants and anti-oxidants status in acne vulgaris patients with varying severity
Addressing Free Radical Oxidationin Acne Vulgari
Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in mice Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in miceHydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen–water enhances5-fluorouracil-induced inhibition of colon cancer Hydrogen–water enhances5-fluorouracil-induced inhibition ofcolon cancerHydrogen–water enhances5-fluorouracil-induced inhibition ofcolon cancerTop of Form
ABSTRACT
Acne vulgaris is a common dermatological disorder with a multifactorial pathogenesis. Oxidative status has been implicated in the pathogenesis of several skin diseases, including acne. This study was aimed to investigate the levels of oxidative stress biomarkers in acne vulgaris patients with varying severities. The study involved 156 patients with acne and 46 healthy human controls.
Based on clinical examination, patients were grouped into 3 subgroups as follows: mild, moderate, and severe acne. Oxidative stress was examined by measuring plasma levels of catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (TAC), and malondialdehyde (MDA). Plasma levels of MDA in acne patients were significantly higher as compared with that of the controls, whereas activities of the antioxidant enzymes SOD and CAT were lower. Moreover, TAC was also low in acne patients as compared with that of the controls. Higher MDA levels in the severe acne subgroup as compared with that of the mild and moderate subgroups were also observed. Furthermore, in the severe acne subgroup, a significant negative correlation was observed between MDA and CAT levels. The data suggests that oxidative stress plays a key role in acne progress and may be employed as a biomarker index to assess the disease’s activity and to monitor its treatment.
References-https://www.ncbi.nlm.nih.gov/pubmed/24795060
Addressing Free Radical Oxidation in Acne Vulgari
Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in mice Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in mice Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancer Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancer Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancerTop of Form
Addressing Free Radical Oxidation in Acne Vulgaris
ABSTRACT
Objective: Comparatively little attention has been paid to the role of free radical oxidation in acne vulgaris. Here, using the traditional abnormalities cited for acne, the authors address the role of free radical oxidation throughout the pathogenesis by detailing the chemistry that may contribute to clinical changes. To probe the effects of free radical oxidation and test an antioxidant, they conducted a preliminary study of topically applied vitamin E.
Methods: Seventeen patients with mild-to-moderate acne vulgaris were evaluated over an eight-week period in two private dermatology practices in this open-label study. All patients enrolled were on the same baseline regimen of salicylic acid and benzoyl peroxide. This regimen was then supplemented with topical vitamin E in sunflower seed oil.
Results: At the end of the eight-week period, all patients demonstrated clinical improvement, as indicated by a reduction in the number of lesions and global mean difference. A statistically significant reduction was noted as early as Week 2. Enrolled patients also expressed a positive experience due to good tolerability and easy application.
Conclusion: Although the exact pathogenesis of acne vulgaris remains unknown, the presence of excessive reactive oxygen species can be implicated in each of the major abnormalities involved. This presence, along with the positive results of the authors’ preliminary study,
demonstrates the need for more exploration on the use of topical antioxidants in limiting free radical oxidation in the acne model. This paper is designed to stimulate academic discussion regarding a new way of thinking about the disease state of acne.
References-https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756869/pdf/jcad_9_1_25.pdf
Hydrogen-rich saline ameliorates the retina against light-induced damage in rats.
ABSTRACT
Oxidative reactions are thought to be a major cause of light-induced retinal degeneration. This study was designed to investigate the effects of hydrogen-rich saline (HRS) on the prevention and treatment of light-induced retinal injury in rats. Male Sprague-Dawley rats were divided randomly into three groups: light damage, HRS prevention (5 ml/kg, 30 min before intensive light exposure), and HRS treatment (5 ml/kg per day for 5 days, after intensive light exposure), respectively. The right eye of each rat was exposed to 5000 lux constant white light-emitting diode (LED) light for 3 h, and the left eye was covered to serve as the blank control. Electroretinograms were recorded 5 days later, and the thickness of the outer nuclear layer (ONL) was measured after hematoxylin and eosin (H&E) staining. The results showed that the electroretinogram b-wave amplitudes and the mean ONL thicknesses of rats were significantly greater in the HRS prevention (P < 0.001) and treatment (P < 0.001) groups than in the light damage. These results indicated that peritoneal injection of HRS provides protection and treatment against light-induced retinal degeneration in rats.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/24004679
Hydrogen-Rich Saline Promotes Survival of Retinal Ganglion Cells in a Rat Model of Optic Nerve Crush
ABSTRACT
Objective: To investigate the effect of molecular hydrogen (H2) in a rat model subjected to optic nerve crush (ONC).
Methods: We tested the hypothesis that after optic nerve crush (ONC), retinal ganglion cell (RGC) could be protected by H2. Rats in different groups received saline or hydrogen-rich saline every day for 14 days after ONC. Retinas from animals in each group underwent measurements of hematoxylin and eosin (H&E) staining, cholera toxin beta (CTB) tracing, gamma synuclein staining, and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) staining 2 weeks post operation. Flash visual evoked potentials (FVEP) and pupillary light reflex (PLR) were then tested to evaluate the function of optic nerve. The malondialdehyde (MDA) level in retina was evaluated.
Results: H&E, gamma synuclein staining and CTB tracing showed that the survival rate of RGCs in hydrogen saline-treated group was significantly higher than that in saline-treated group. Apoptosis of RGCs assessed by TUNEL staining were less observed in hydrogen saline-treated group. The MDA level in retina of H2 group was much lower than that in placebo group. Furthermore, animals treated with hydrogen saline showed better function of optic nerve in assessments of FVEP and PLR.
Conclusion: These results demonstrated that H2 protects RGCs and helps preserve the visual function after ONC and had a neuroprotective effect in a rat model subjected to ONC.
Reference-https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0099299
Inhalation of hydrogen gas attenuates ouabain-induced auditory neuropathy in gerbils.
ABSTRACT
AIM: Auditory neuropathy (AN) is a hearing disorder characterized by abnormal auditory nerve function with preservation of normal cochlear hair cells. This study was designed to investigate whether treatment with molecular hydrogen (H(2)), which can remedy damage in various organs via reducing oxidative stress, inflammation and apoptosis, is beneficial to ouabain-induced AN in gerbils.
METHODS: AN model was made by local application of ouabain (1 mmol/L, 20 mL) to the round window membrane in male Mongolian gerbils. H(2) treatment was given twice by exposing the animals to H(2) (1%, 2%, and 4%) for 60 min at 1 h and 6 h after ouabain application. Before and 7 d after ouabain application, the hearing status of the animals was evaluated using the auditory brainstem response (ABR) approach, the hear cell function was evaluated with distortion product otoacoustic emissions (DPOAE). Seven days after ouabain application, the changes in the cochleae, especially the spiral ganglion neurons (SGNs), were morphologically studied. TUNEL staining and immunofluorescent staining for activated caspase-3 were used to assess the apoptosis of SGNs.
RESULTS: Treatment with H(2) (2% and 4%) markedly attenuated the click and tone burst-evoked ABR threshold shift at 4, 8, and 16 kHz in ouabain-exposed animals. Neither local ouabain application, nor H(2) treatment changed the amplitude of DPOAE at 4, 8, and 16 kHz. Morphological study showed that treatment with H(2) (2%) significantly alleviated SGN damage and attenuated the loss of SGN density for each turn of cochlea in ouabain-exposed animals. Furthermore, ouabain caused significantly higher numbers of apoptotic SGNs in the cochlea, which was significantly attenuated by the H(2) treatment. However, ouabain did not change the morphology of cochlear hair cells.
CONCLUSION: The results demonstrate that H(2) treatment is beneficial to ouabain-induced AN via reducing apoptosis. Thus, H(2) might be a potential agent for treating hearing impairment in AN patients.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/22388074
Hydrogen(H2) treatment for acute erythymatous skin diseases. A report of 4 patients with safety data and a non-controlled feasibility study with H2 concentration measurement on two volunteers.
ABSTRACT
BACKGROUND: We have treated 4 patients of acute erythematous skin diseases with fever and/or pain by H2 enriched intravenous fluid. We also added data from two volunteers for assessing the mode of H2 delivery to the skin for evaluation of feasibility of H2 treatment for this type of skin diseases.
METHODS: All of the four patients received intravenous administration of 500 ml of H2 enriched fluid in 30 min for more than 3 days except in one patient for only once. From two volunteers (one for intravenous H2 administration and the other for H2 inhalation), blood samples were withdrawn serially and air samples were collected from a heavy duty plastic bag covering a leg, before, during and after H2 administration. These samples were checked for H2 concentration immediately by gas chromatography. Multiple physiological parameters and blood chemistry data were collected also.
RESULTS: Erythema of these 4 patients and associated symptoms improved significantly after the H2 treatment and did not recur. Administration of H2 did not change physiological parameters and did not cause deterioration of the blood chemistry. The H2 concentration in the blood from the volunteers rapidly increased with H2 inhalation and slowly decreased with cessation of H2 particularly in the venous blood, while H2 concentration of the air from the surface of the leg showed much slower changes even after H2 inhalation was discontinued, at least during the time of sample collection.
CONCLUSION: An improvement in acute erythemtous skin diseases followed the administration of H2 enriched fluid without compromising the safety. The H2 delivery study of two volunteers suggested initial direct delivery and additional prolonged delivery possibly from a slowly desaturating reservoir in the skin to the surface.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/22607973
Hydrogen-rich saline ameliorates the retina against light-induced damage in rats.
ABSTRACT
Oxidative reactions are thought to be a major cause of light-induced retinal degeneration. This study was designed to investigate the effects of hydrogen-rich saline (HRS) on the prevention and treatment of light-induced retinal injury in rats. Male Sprague-Dawley rats were divided randomly into three groups: light damage, HRS prevention (5 ml/kg, 30 min before intensive light exposure), and HRS treatment (5 ml/kg per day for 5 days, after intensive light exposure), respectively. The right eye of each rat was exposed to 5000 lux constant white light-emitting diode (LED) light for 3 h, and the left eye was covered to serve as the blank control. Electroretinograms were recorded 5 days later, and the thickness of the outer nuclear layer (ONL) was measured after hematoxylin and eosin (H&E) staining. The results showed that the electroretinogram b-wave amplitudes and the mean ONL thicknesses of rats were significantly greater in the HRS prevention (P < 0.001) and treatment (P < 0.001) groups than in the light damage. These results indicated that peritoneal injection of HRS provides protection and treatment against light-induced retinal degeneration in rats.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/24004679
Hydrogen-Rich Saline Promotes Survival of Retinal Ganglion Cells in a Rat Model of Optic Nerve Crush
ABSTRACT
Objective:To investigate the effect of molecular hydrogen (H2) in a rat model subjected to optic nerve crush (ONC).
Methods:We tested the hypothesis that after optic nerve crush (ONC), retinal ganglion cell (RGC) could be protected by H2. Rats in different groups received saline or hydrogen-rich saline every day for 14 days after ONC. Retinas from animals in each group underwent measurements of hematoxylin and eosin (H&E) staining, cholera toxin beta (CTB) tracing, gamma synuclein staining, and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) staining 2 weeks post operation. Flash visual evoked potentials (FVEP) and pupillary light reflex (PLR) were then tested to evaluate the function of optic nerve. The malondialdehyde (MDA) level in retina was evaluated.
Results: H&E, gamma synuclein staining and CTB tracing showed that the survival rate of RGCs in hydrogen saline-treated group was significantly higher than that in saline-treated group. Apoptosis of RGCs assessed by TUNEL staining were less observed in hydrogen saline-treated group. The MDA level in retina of H2 group was much lower than that in placebo group. Furthermore, animals treated with hydrogen saline showed better function of optic nerve in assessments of FVEP and PLR.
Conclusion: These results demonstrated that H2 protects RGCs and helps preserve the visual function after ONC and had a neuroprotective effect in a rat model subjected to ONC.
Reference-https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0099299
Inhalation of hydrogen gas attenuates ouabain-induced auditory neuropathy in gerbils.
ABSTRACT
AIM: Auditory neuropathy (AN) is a hearing disorder characterized by abnormal auditory nerve function with preservation of normal cochlear hair cells. This study was designed to investigate whether treatment with molecular hydrogen (H(2)), which can remedy damage in various organs via reducing oxidative stress, inflammation and apoptosis, is beneficial to ouabain-induced AN in gerbils.
METHODS: AN model was made by local application of ouabain (1 mmol/L, 20 mL) to the round window membrane in male Mongolian gerbils. H(2) treatment was given twice by exposing the animals to H(2) (1%, 2%, and 4%) for 60 min at 1 h and 6 h after ouabain application. Before and 7 d after ouabain application, the hearing status of the animals was evaluated using the auditory brainstem response (ABR) approach, the hear cell function was evaluated with distortion product otoacoustic emissions (DPOAE). Seven days after ouabain application, the changes in the cochleae, especially the spiral ganglion neurons (SGNs), were morphologically studied. TUNEL staining and immunofluorescent staining for activated caspase-3 were used to assess the apoptosis of SGNs.
RESULTS: Treatment with H(2) (2% and 4%) markedly attenuated the click and tone burst-evoked ABR threshold shift at 4, 8, and 16 kHz in ouabain-exposed animals. Neither local ouabain application, nor H(2) treatment changed the amplitude of DPOAE at 4, 8, and 16 kHz. Morphological study showed that treatment with H(2) (2%) significantly alleviated SGN damage and attenuated the loss of SGN density for each turn of cochlea in ouabain-exposed animals. Furthermore, ouabain caused significantly higher numbers of apoptotic SGNs in the cochlea, which was significantly attenuated by the H(2) treatment. However, ouabain did not change the morphology of cochlear hair cells.
CONCLUSION: The results demonstrate that H(2) treatment is beneficial to ouabain-induced AN via reducing apoptosis. Thus, H(2) might be a potential agent for treating hearing impairment in AN patients.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/22388074
Recent Progress Toward Hydrogen Medicine: Potential of Molecular Hydrogen for Preventive and Therapeutic Applications
ABSTRACT
Persistent oxidative stress is one of the major causes of most lifestyle-related diseases, cancer and the aging process. Acute oxidative stress directly causes serious damage to tissues. Despite the clinical importance of oxidative damage, antioxidants have been of limited therapeutic success. We have proposed that molecular hydrogen (H2) has potential as a “novel” antioxidant in preventive and therapeutic applications [Ohsawa et al., Nat Med. 2007: 13; 688-94]. H2 has a number of advantages as a potential antioxidant: H2 rapidly diffuses into tissues and cells, and it is mild enough neither to disturb metabolic redox reactions nor to affect reactive oxygen species (ROS) that function in cell signaling, thereby, there should be little adverse effects of consuming H2. There are several methods to ingest or consume H2, including inhaling hydrogen gas, drinking H2-dissolved water (hydrogen water), taking a hydrogen bath, injecting H2-dissolved saline (hydrogen saline), dropping hydrogen saline onto the eye, and increasing the production of intestinal H2 by bacteria. Since the publication of the first H2 paper in Nature Medicine in 2007, the biological effects of H2 have been confirmed by the publication of more than 38 diseases, physiological states and clinical tests in leading biological/medical journals, and several groups have started clinical examinations. Moreover, H2 shows not only effects against oxidative stress, but also various anti-inflammatory and anti-allergic effects. H2 regulates various gene expressions and protein-phosphorylations, though the molecular mechanisms underlying the marked effects of very small amounts of H2 remain elusive.
Reference–https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257754/
Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals.
ABSTRACT
Acute oxidative stress induced by ischemia-reperfusion or inflammation causes serious damage to tissues, and persistent oxidative stress is accepted as one of the causes of many common diseases including cancer. We show here that hydrogen (H(2)) has potential as an antioxidant in preventive and therapeutic applications. We induced acute oxidative stress in cultured cells by three independent methods. H(2) selectively reduced the hydroxyl radical, the most cytotoxic of reactive oxygen species (ROS), and effectively protected cells; however, H(2) did not react with other ROS, which possess physiological roles. We used an acute rat model in which oxidative stress damage was induced in the brain by focal ischemia and reperfusion. The inhalation of H(2) gas markedly suppressed brain injury by buffering the effects of oxidative stress. Thus H(2) can be used as an effective antioxidant therapy; owing to its ability to rapidly diffuse across membranes, it can reach and react with cytotoxic ROS and thus protect against oxidative damage
Reference–https://www.ncbi.nlm.nih.gov/pubmed/17486089
Hydrogen as a Selective Antioxidant: A Review of Clinical and Experimental Studies
ABSTRACT
Oxidative stress is implicated in the pathogenesis of many diseases; however, currently used antioxidants have a high toxicity that constrains administration to a narrow window of therapeutic dosage. There is a clear need for more effective and safer antioxidants. Diatomic hydrogen (H2) was proposed as a novel antioxidant that selectively reduces levels of toxic reactive-oxygen species. Recently, many studies have reported that H2 (inhaled or orally ingested, typically as approximately 0.8 mM H2-saturated water), can exert beneficial effects in diverse animal models of ischaemia–reperfusion injury, and inflammatory and neurological disease. In the clinic, oral administration of H2-saturated water is reported to improve lipid and glucose metabolism in subjects with diabetes or impaired glucose tolerance; promising results have also been obtained in reducing inflammation in haemodialysis patients and treating metabolic syndrome. These studies suggest H2 has selective antioxidant properties, and can exert antiapoptotic, anti-inflammatory and antiallergy effects. This review summarizes recent research findings and mechanisms concerning the therapeutic potential of H2.
Reference-https://journals.sagepub.com/doi/abs/10.1177/147323001003800602
Pilot study: Effects of drinking hydrogen-rich water on muscle fatigue caused by acute exercise in elite athletes
ABSTRACT
Background: Muscle contraction during short intervals of intense exercise causes oxidative stress, which can play a role in the development of overtraining symptoms, including increased fatigue, resulting in muscle microinjury or inflammation. Recently it has been said that hydrogen can function as antioxidant, so we investigated the effect of hydrogen-rich water (HW) on oxidative stress and muscle fatigue in response to acute exercise.
Methods: Ten male soccer players aged 20.9 ± 1.3 years old were subjected to exercise tests and blood sampling. Each subject was examined twice in a crossover double-blind manner; they were given either HW or placebo water (PW) for one week intervals. Subjects were requested to use a cycle ergometer at a 75 % maximal oxygen uptake (VO2) for 30 min, followed by measurement of peak torque and muscle activity throughout 100 repetitions of maximal isokinetic knee extension. Oxidative stress markers and creatine kinase in the peripheral blood were sequentially measured.
Results: Although acute exercise resulted in an increase in blood lactate levels in the subjects given PW, oral intake of HW prevented an elevation of blood lactate during heavy exercise. Peak torque of PW significantly decreased during maximal isokinetic knee extension, suggesting muscle fatigue, but peak torque of HW didn’t decrease at early phase. There was no significant change in blood oxidative injury markers (d-ROMs and BAP) or creatine kinease after exercise.
Conclusion: Adequate hydration with hydrogen-rich water pre-exercise reduced blood lactate levels and improved exercise-induced decline of muscle function. Although further studies to elucidate the exact mechanisms and the benefits are needed to be confirmed in larger series of studies, these preliminary results may suggest that HW may be suitable hydration for athletes.
Reference-https://medicalgasresearch.biomedcentral.com/articles/10.1186/2045-9912-2-12
Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in mice
ABSTRACT
AIM: To investigate the hepatoprotective effects and mechanisms of hydrogen-rich water (HRW) in acetaminophen (APAP)-induced liver injury in mice.
METHODS: Male mice were randomly divided into the following four groups: normal saline (NS) control group, mice received equivalent volumes of NS intraperitoneally (ip); HRW control group, mice were given HRW (same volume as the NS group); APAP + NS group, mice received NS ip for 3 d (5 mL/kg body weight, twice a day at 8 am and 5 pm) after APAP injection; APAP + HRW group, mice received HRW for 3 d (same as NS treatment) after APAP challenge. In the first experiment, mice were injected ip with a lethal dose of 750 mg/kg APAP to determine the 5-d survival rates. In the second experiment, mice were injected ip with a sub-lethal dose of 500 mg/kg. Blood and liver samples were collected at 24, 48, and 72 h after APAP injection to determine the degree of liver injury.
RESULTS: Treatment with HRW resulted in a significant increase in the 5-d survival rate compared with the APAP + NS treatment group (60% vs 26.67%, P < 0.05). HRW could significantly decrease the serum alanine aminotransferase level (24 h: 4442 ± 714.3 U/L vs 6909 ± 304.8 U/L, P < 0.01; 48 h: 3782 ± 557.5 U/L vs 5111 ± 404 U/L, P < 0.01; and 3255 ± 337.4 U/L vs 3814 ± 250.2 U/L, P < 0.05, respectively) and aspartate aminotransferase level (24 h: 4683 ± 443.4 U/L vs 5307 ± 408.4 U/L, P < 0.05; 48 h: 3392 ± 377.6 U/L vs 4458 ± 423.6 U/L, P < 0.01; and 3354 ± 399.4 U/L vs 3778 ± 358 U/L, respectively) compared with the APAP treatment group. The alkaline phosphatase, total bilirubin and lactate dehydrogenase levels had the same result. Seventy-two hours after APAP administration, liver samples were collected for pathological examination and serum was collected to detect the cytokine levels. The liver index (5.16% ± 0.26% vs 5.88% ± 0.073%, P < 0.05) and percentage of liver necrosis area (27.73% ± 0.58% vs 36.87% ± 0.49%, P < 0.01) were significantly lower in the HRW-treated animals. The malonyldialdehyde (MDA) contents were significantly reduced in the HRW pretreatment group, but they were increased in the APAP-treated group (10.44 ± 1.339 nmol/mg protein vs 16.70 ± 1.646 nmol/mg protein, P < 0.05). A decrease in superoxide dismutase (SOD) activity in the APAP treatment group and an increase of SOD in the HRW treatment group were also detected (9.74 ± 0.46 U/mg protein vs 12.1 ± 0.67 U/mg protein, P < 0.05). Furthermore, HRW could significantly increase the glutathione (GSH) contents (878.7 ± 76.73 mg/g protein vs 499.2 ± 48.87 mg/g protein) compared with the APAP treatment group. Meanwhile, HRW could reduce the inflammation level (serum TNF-α: 399.3 ± 45.50 pg/L vs 542.8 ± 22.38 pg/L, P < 0.05; and serum IL-6: 1056 ± 77.01 pg/L vs 1565 ± 42.11 pg/L, P < 0.01, respectively). In addition, HRW could inhibit 4-HNE, nitrotyrosine formation, JNK phosphorylation, connexin 32 and cytochrome P4502E expression. Simultaneously, HRW could facilitate hepatocyte mitosis to promote liver regeneration.
CONCLUSION: HRW has significant therapeutic potential in APAP-induced hepatotoxicity by inhibiting oxidative stress and inflammation and promoting liver regeneration.
Reference-https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394080/
Hydrogen Gas Presents a Promising Therapeutic Strategy for Sepsis
ABSTRACT
Sepsis is characterized by a severe inflammatory response to infection. It remains a major cause of morbidity and mortality in critically ill patients despite developments in monitoring devices, diagnostic tools, and new therapeutic options. Recently, some studies have found that molecular hydrogen is a new therapeutic gas. Our studies have found that hydrogen gas can improve the survival and organ damage in mice and rats with cecal ligation and puncture, zymosan, and lipopolysaccharide-induced sepsis. The mechanisms are associated with the regulation of oxidative stress, inflammatory response, and apoptosis, which might be through NF-κB and Nrf2/HO-1 signaling pathway. In this paper, we summarized the progress of hydrogen treatment in sepsis.
Reference-https://www.hindawi.com/journals/bmri/2014/807635/
Molecular Hydrogen as an Emerging Therapeutic Medical Gas for Neurodegenerative and Other Diseases
ABSTRACT
Effects of molecular hydrogen on various diseases have been documented for 63 disease models and human diseases in the past four and a half years. Most studies have been performed on rodents including two models of Parkinson’s disease and three models of Alzheimer’s disease. Prominent effects are observed especially in oxidative stress-mediated diseases including neonatal cerebral hypoxia; Parkinson’s disease; ischemia/reperfusion of spinal cord, heart, lung, liver, kidney, and intestine; transplantation of lung, heart, kidney, and intestine. Six human diseases have been studied to date: diabetes mellitus type 2, metabolic syndrome, hemodialysis, inflammatory and mitochondrial myopathies, brain stem infarction, and radiation-induced adverse effects. Two enigmas, however, remain to be solved. First, no dose-response effect is observed. Rodents and humans are able to take a small amount of hydrogen by drinking hydrogen-rich water, but marked effects are observed. Second, intestinal bacteria in humans and rodents produce a large amount of hydrogen, but an addition of a small amount of hydrogen exhibits marked effects. Further studies are required to elucidate molecular bases of prominent hydrogen effects and to determine the optimal frequency, amount, and method of hydrogen administration for each human disease.
Reference-https://www.hindawi.com/journals/omcl/2012/353152/
Beneficial biological effects and the underlying mechanisms of molecular hydrogen – comprehensive review of 321 original articles –
ABSTRACT
Therapeutic effects of molecular hydrogen for a wide range of disease models and human diseases have been investigated since 2007. A total of 321 original articles have been published from 2007 to June 2015. Most studies have been conducted in Japan, China, and the USA. About three-quarters of the articles show the effects in mice and rats. The number of clinical trials is increasing every year. In most diseases, the effect of hydrogen has been reported with hydrogen water or hydrogen gas, which was followed by confirmation of the effect with hydrogen-rich saline. Hydrogen water is mostly given ad libitum. Hydrogen gas of less than 4 % is given by inhalation. The effects have been reported in essentially all organs covering 31 disease categories that can be subdivided into 166 disease models, human diseases, treatment-associated pathologies, and pathophysiological conditions of plants with a predominance of oxidative stress-mediated diseases and inflammatory diseases. Specific extinctions of hydroxyl radical and peroxynitrite were initially presented, but the radical-scavenging effect of hydrogen cannot be held solely accountable for its drastic effects. We and others have shown that the effects can be mediated by modulating activities and expressions of various molecules such as Lyn, ERK, p38, JNK, ASK1, Akt, GTP-Rac1, iNOS, Nox1, NF-κB p65, IκBα, STAT3, NFATc1, c-Fos, and ghrelin. Master regulator(s) that drive these modifications, however, remain to be elucidated and are currently being extensively investigated.
Reference-https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4610055/
The evolution of molecular hydrogen: a noteworthy potential therapy with clinical significance
ABSTRACT
Studies on molecular hydrogen have evolved tremendously from its humble beginnings and have continued to change throughout the years. Hydrogen is extremely unique since it has the capability to act at the cellular level. Hydrogen is qualified to cross the blood brain barrier, to enter the mitochondria, and even has the ability to translocate to the nucleus under certain conditions. Once in these ideal locations of the cell, previous studies have shown that hydrogen exerts antioxidant, anti-apoptotic, anti-inflammatory, and cytoprotective properties that are beneficial to the cell. Hydrogen is most commonly applied as a gas, water, saline, and can be applied in a variety of other mediums. There are also few side effects involving hydrogen, thus making hydrogen a perfect medical gas candidate for the convention of novel therapeutic strategies against cardiovascular, cerebrovascular, cancer, metabolic, and respiratory diseases and disorders. Although hydrogen appears to be faultless at times, there still are several deficiencies or snares that need to be investigated by future studies. This review article seeks to delve and comprehensively analyze the research and experiments that alludes to molecular hydrogen being a novel therapeutic treatment that medicine desperately needs.
Reference-https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660246/
The Drinking Effect of Hydrogen Water on Atopic Dermatitis Induced by Dermatophagoides farinae Allergen in NC/Nga Mice
ABSTRACT
Hydrogen water (HW) produced by electrolysis of water has characteristics of extremely low oxidation-reduction potential (ORP) value and high dissolved hydrogen (DH). It has been proved to have various beneficial effects including antioxidant and anti-inflammatory effects; however, HW effect on atopic dermatitis (AD), an inflammatory skin disorder, is poorly documented. In the present study, we examined the immunological effect of drinking HW on Dermatophagoides farinae-induced AD-like skin in NC/Nga mice. Mice were administered with HW and purified water (PW) for 25 days. We evaluated the serum concentration of pro-inflammatory (TNF-α), Th1 (IFN-γ, IL-2, and IL-12p70), Th2 (IL-4, IL-5, and IL-10), and cytokine expressed by both subsets (GM-CSF) to assess their possible relationship to the severity of AD. The serum levels of cytokines such as IL-10, TNF-α, IL-12p70, and GM-CSF of mice administered with HW was significantly reduced as compared to PW group. The results suggest that HW affects allergic contact dermatitis through modulation of Th1 and Th2 responses in NC/Nga mice. This is the first note on the drinking effect of HW on AD, clinically implying a promising potential remedy for treatment of AD.
Reference-https://www.hindawi.com/journals/ecam/2013/538673/
Molecular hydrogen in drinking water protects against neurodegenerative changes induced by traumatic brain injury
ABSTRACT
Traumatic brain injury (TBI) in its various forms has emerged as a major problem for modern society. Acute TBI can transform into a chronic condition and be a risk factor for neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases, probably through induction of oxidative stress and neuroinflammation.
Here, we examined the ability of the antioxidant molecular hydrogen given in drinking water (molecular hydrogen water; mHW) to alter the acute changes induced by controlled cortical impact (CCI), a commonly used experimental model of TBI. We found that mHW reversed CCI-induced edema by about half, completely blocked pathological tau expression, accentuated an early increase seen in several cytokines but attenuated that increase by day 7, reversed changes seen in the protein levels of aquaporin-4, HIF-1, MMP-2, and MMP-9, but not for amyloid beta peptide 1-40 or 1-42.
Treatment with mHW also reversed the increase seen 4 h after CCI in gene expression related to oxidation/carbohydrate metabolism, cytokine release, leukocyte or cell migration, cytokine transport, ATP and nucleotide binding. Finally, we found that mHW preserved or increased ATP levels and propose a new mechanism for mHW, that of ATP production through the Jagendorf reaction. These results show that molecular hydrogen given in drinking water reverses many of the sequelae of CCI and suggests that it could be an easily administered, highly effective treatment for TBI.
References– https://www.ncbi.nlm.nih.gov/pubmed/25251220
Hydrogen improves neurological function through attenuation of blood–brain barrier disruption in spontaneously hypertensive stroke-prone rats
ABSTRACT
Background: Enhanced oxidative stress occurs in spontaneously hypertensive stroke-prone rats (SHRSP), and is important in blood–brain barrier (BBB) disruption. Hydrogen can exert potent protective cellular effects via reduction in oxidative stress in various diseases. The present study investigated whether long-term hydrogen treatment can improve neurological function outcome in the SHRSP model, and the effects of hydrogen on BBB function, especially the oxidative stress and the activity of matrix metalloproteinases (MMPs) in this model. Fifty-six animals were randomly assigned to 2 groups and treated as follows: SHRSP treated with hydrogen-rich water (HRW) (HRW group, n = 28); and SHRSP treated with regular water (control group, n = 28). The effect of HRW on overall survival and neurological function, and the effects of HRW on reactive oxygen species, BBB function, and MMP activities were examined.
Results: HRW treatment improved neurological function and tended to improve overall survival but without significant difference. The numbers of bleeds and infarcts were lower in the cortex and hippocampus in the HRW group. The HRW group exhibited a significantly lower number of 8-hydroxy-2′-deoxyguanosine-positive cells and vessels of extravasated albumin in the hippocampus compared with the control group. MMP-9 activity was reduced in the hippocampus in the HRW group compared with the control group.
Conclusions: The present study suggests that ingestion of HRW can improve neurological function outcome in the SHRSP model. This beneficial effect may be due to attenuation of BBB disruption via reduction in reactive oxygen species and suppression of MMP-9 activity in the hippocampus.
References-https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4411925/
Oxidants and anti-oxidants status in acne vulgaris patients with varying severity
Addressing Free Radical Oxidationin Acne Vulgari
Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in mice Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in miceHydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen–water enhances5-fluorouracil-induced inhibition of colon cancer Hydrogen–water enhances5-fluorouracil-induced inhibition ofcolon cancerHydrogen–water enhances5-fluorouracil-induced inhibition ofcolon cancerTop of Form
ABSTRACT
Acne vulgaris is a common dermatological disorder with a multifactorial pathogenesis. Oxidative status has been implicated in the pathogenesis of several skin diseases, including acne. This study was aimed to investigate the levels of oxidative stress biomarkers in acne vulgaris patients with varying severities. The study involved 156 patients with acne and 46 healthy human controls.
Based on clinical examination, patients were grouped into 3 subgroups as follows: mild, moderate, and severe acne. Oxidative stress was examined by measuring plasma levels of catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (TAC), and malondialdehyde (MDA). Plasma levels of MDA in acne patients were significantly higher as compared with that of the controls, whereas activities of the antioxidant enzymes SOD and CAT were lower. Moreover, TAC was also low in acne patients as compared with that of the controls. Higher MDA levels in the severe acne subgroup as compared with that of the mild and moderate subgroups were also observed. Furthermore, in the severe acne subgroup, a significant negative correlation was observed between MDA and CAT levels. The data suggests that oxidative stress plays a key role in acne progress and may be employed as a biomarker index to assess the disease’s activity and to monitor its treatment.
References-https://www.ncbi.nlm.nih.gov/pubmed/24795060
Effects of hydrogen-rich water on depressive-like behavior in mice
ABSTRACT
Emerging evidence suggests that neuroinflammation and oxidative stress may be major contributors to major depressive disorder (MDD). Patients or animal models of depression show significant increase of proinflammatory cytokine interleukin-1β (IL-1β) and oxidative stress biomarkers in the periphery or central nervous system (CNS). Recent studies show that hydrogen selectively reduces cytotoxic oxygen radicals, and hydrogen-rich saline potentially suppresses the production of several proinflammatory mediators. Since current depression medications are accompanied by a wide spectrum of side effects, novel preventative or therapeutic measures with fewer side effects might have a promising future. We investigated the effects of drinking hydrogen-rich water on the depressive-like behavior in mice and its underlying mechanisms. Our study show that hydrogen-rich water treatment prevents chronic unpredictable mild stress (CUMS) induced depressive-like behavior. CUMS induced elevation in IL-1β protein levels in the hippocampus, and the cortex was significantly attenuated after 4 weeks of feeding the mice hydrogen-rich water. Over-expression of caspase-1 (the IL-1β converting enzyme) and excessive reactive oxygen species (ROS) production in the hippocampus and prefrontal cortex (PFC) was successfully suppressed by hydrogen-rich water treatment. Our data suggest that the beneficial effects of hydrogen-rich water on depressive-like behavior may be mediated by suppression of the inflammasome activation resulting in attenuated protein IL-1β and ROS production.
Major depressive disorder (MDD) is a pervasive mental disorder that affects about 350 million people across the world. MDD ranks as the 11th leading cause of disability-adjusted life years (DALYs), according to Global Burden of Disease studies measuring disease burden worldwide. Decades of extensive studies in the pathophysiology of MDD have led to various hypotheses for the molecular basis of depression. Patients suffering from depression often display evidence of an inflammation characterized by the increased expression of proinflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor (TNF). Proinflammatory cytokines can elicit sickness behavior and induce depressive-like neuroendocrine and central neurotransmitter changes which can be exacerbated by stressors4. Together, evidence from clinical and animal studies have led to the hypothesis that chronic cytokines expression may cause depressive illness in human beings.
Cytokines in the periphery access the brain partly via afferent vagus nerve to elicit a sickness response in the central nervous system. Peripheral nerve injury contributes to the development of depressive-like behavior via increasing cytokine expression. Stress facilitates this process by promoting the up-regulation of inflammatory cytokines such as IL-1β gene expression in the brain7. As a major regulator of stress responses, IL-1β can promote coping at low levels while exerting detrimental effects at high levels. Studies by Goshen and colleagues demonstrate that elevation of brain IL-1 levels is necessary and sufficient for the development of depression.
The expression and activation of the proinflammatory cytokine IL-1β is dependent on the assembly and activation of an intracellular protein complex called the inflammasome. Upon cellular infection or stress, the inflammasome complex mediate activation of Caspase-1 to promote the maturation of pro-IL-1β to its fully functional IL-1β form. Interestingly, inflammasome dependent neuroinflammation pathways have recently been implicated in several CNS psychiatric illnesses. Recent reports and reviews link inflammasome activation with major depressive disorder (MDD), and suggest that inflammasome activation may play a central role in the development of depressive-like behaviors. Moreover, the NLRP3 inflammasome has been identified as a potential therapeutic target for alleviating neuroinflammation and for treatment of MDD.
Oxidative stress may be a crucial contributor to the development of MDD. Patients with MDD show increased expression of inflammatory and oxidative stress biomarkers14. Oxidative stress results from a breakdown in homeostasis between reactive oxygen species (ROS) and antioxidants. Antioxidants can protect against ROS-induced neuronal damage by scavenging radicals and suppressing the oxidative stress pathway in the brain. Notably, Xu and colleagues have recently proposed antioxidants as a candidate treatment for depression, based on the reviews of recent studies on oxidative stress markers in patients and animal models of depression.
Hydrogen selectively reduces cytotoxic oxygen radicals, and may potentially serve as a novel antioxidant in preventive and therapeutic applications. Hydrogen-saline has been shown to be more convenient and efficient in protecting against inflammation than inhaling hydrogen gas. Zhang and colleagues has reported that pretreatment with hydrogen-rich water could mitigate aspirin-induced gastric lesions through the inhibition of the oxidative stress and inflammatory reactions. Hydrogen-rich saline suppresses the production of several proinflammatory mediators by inhibiting the activation of p38 and NF-κB. Furthermore, the therapeutic effects of hydrogen-rich saline in acute lung injury may be due to its antioxidant and anti-inflammatory actions. Tomofuji and colleagues proposed that drinking hydrogen-rich water had anti-oxidative damage effects on aging periodontal tissues.
Classic antidepressants, which are effective in less than 50% of patients, are often associated with a wide range of undesired side effects. Therefore, identifying effective anti-depressive compounds with little to no side effects may serve as effective alternative or preventative treatments. It is unclear if hydrogen-rich water, which has no known side effects, may have beneficial effects in mitigating depression symptoms. We therefore investigated the preventative effects of hydrogen-rich water on the development of depressive-like behavior in the chronic unpredictable mild stress (CUMS) mouse model. We measured protein levels of IL-1β, detected caspase-1 activation and ROS production in the hippocampus and prefrontal cortex (PFC) to determine if hydrogen-rich water may exert its potential beneficial effects on depressive-like behavior. Our results demonstrate that hydrogen-rich water attenuates stress induced oxidative stress and neuroinflammation, in turn, preventing the development and progression of depressive-like behaviors following chronic stress exposure.
References-https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4812321/
Molecular hydrogen reduces LPS-induced neuroinflammation and promotes recovery from sickness behaviour in mice
ABSTRACT
Molecular hydrogen has been shown to have neuroprotective effects in mouse models of acute neurodegeneration. The effect was suggested to be mediated by its free-radical scavenger properties. However, it has been shown recently that molecular hydrogen alters gene expression and protein phosphorylation. The aim of this study was to test whether chronic ad libitum consumption of molecular hydrogen-enriched electrochemically reduced water (H-ERW) improves the outcome of lipopolysaccharide (LPS)-induced neuroinflammation. Seven days after the initiation of H-ERW treatment, C57Bl/6 mice received a single injection of LPS (0.33 mg/kg i.p.) or an equivalent volume of vehicle. The LPS-induced sickness behaviour was assessed 2 h after the injection, and recovery was assessed by monitoring the spontaneous locomotor activity in the homecage for 72 h after the administration of LPS. The mice were killed in the acute or recovery phase, and the expression of pro- and antiinflammatory cytokines in the hippocampus was assessed by real-time PCR. We found that molecular hydrogen reduces the LPS-induced sickness behaviour and promotes recovery. These effects are associated with a shift towards anti-inflammatory gene expression profile at baseline (downregulation of TNF- α and upregulation of IL-10). In addition, molecular hydrogen increases the amplitude, but shortens the duration and promotes the extinction of neuroinflammation. Consistently, molecular hydrogen modulates the activation and gene expression in a similar fashion in immortalized murine microglia (BV-2 cell line), suggesting that the effects observed in vivo may involve the modulation of microglial activation. Taken together, our data point to the regulation of cytokine expression being an additional critical mechanism underlying the beneficial effects of molecular hydrogen.
References-https://www.ncbi.nlm.nih.gov/pubmed/22860058
Inhalation of hydrogen gas attenuates brain injury in mice with cecal ligation and puncture via inhibiting neuroinflammation, oxidative stress and neuronal apoptosis
ABSTRACT
During the development of sepsis, the complication in central nervous system (CNS), appearing early and frequently relative to other systems, can obviously increase the mortality of sepsis. Moreover, sepsis survivors also accompany long-term cognitive dysfunction, while the ultimate causes and effective therapeutic strategies of brain injury in sepsis are still not fully clear. We designed this study to investigate the effects of 2% hydrogen gas (H2) on brain injury in a mouse model of sepsis. Male ICR mice were underwent cecal ligation and puncture (CLP) or sham operation. 2% H2 was inhaled for 60min beginning at both 1 and 6h after sham or CLP operation, respectively. H2 concentration in arterial blood, venous blood and brain tissue was detected after H2 inhalation separately. The survival rate was observed and recorded within 7 days after sham or CLP operation. The histopathologic changes and neuronal apoptosis were observed in hippocampus by Nissl staining and TUNEL assay. The permeability of brain-blood barrier (BBB), brain water content, inflammatory cytokines, activities of antioxidant enzymes (SOD and CAT) and oxidative products (MDA and 8-iso-PGF2α) in serum and hippocampus were detected at 24h after sham or CLP operation. The expressions of nucleus and total nuclear factor erythroid 2-related factor 2 (Nrf2) and cytoplasmic heme oxygenase-1(HO-1) in hippocampus were measured at 24h after sham or CLP operation. We assessed their cognitive function via Y-maze and Fear Conditioning test on day 3, 5, 7 and 14 after operation. H2 treatment markedly improved the survival rate and cognitive dysfunction of septic mice. CLP mice showed obvious brain injury characterized by aggravated pathological damage, BBB disruption and brain edema at 24h after CLP operation, which was markedly alleviated by 2% H2 treatment. Furthermore, we found that the beneficial effects of H2 on brain injury in septic mice were linked to the decreased levels of inflammatory cytokines and oxidative products and the increased activities of antioxidant enzymes in serum and hippocampus. In addition, 2% H2 inhalation promoted the expression and transposition of Nrf2 and the expression of HO-1 to mitigate brain injury in sepsis. Thus, the inhalation of hydrogen gas may be a promising therapeutic strategy to relieve brain injury in sepsis.
References-https://www.ncbi.nlm.nih.gov/pubmed/25251596
Effects of Hydrogen-Rich Saline on Hepatectomy-Induced Postoperative Cognitive Dysfunction in Old Mice
ABSTRACT
This study aims to investigate the protective effects and underlying mechanisms of hydrogen-rich saline on the cognitive functions of elder mice with partial hepatectomy-induced postoperative cognitive dysfunction (POCD). Ninety-six old male Kunming mice were randomly divided into 4 groups (n = 24 each): control group (group C), hydrogen-rich saline group (group H), POCD group (group P), and POCD + hydrogen-rich saline group (group PH). Cognitive function was subsequently assessed using Morris water-maze (MWM) test. TNF-α and IL-1β levels were measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, along with NF-κB activity determined by ELISA. The morphology of hippocampal tissues were further observed by HE staining. Learning and memory abilities of mice were significantly impaired at day 10 and day 14 post-surgery, as partial hepatectomy significantly prolonged the escape latency, decreased time at the original platform quadrant and frequency of crossing in group P when compared to group C (p < 0.05). The surgery also increased the contents of TNF-α, IL-1β, and NF-κB activity at all time points after surgery (p < 0.05). The introduction of hydrogen-rich saline (group PH) partially rescued spatial memory and learning as it shortened escape latency and increased time and crossing frequency of original platform compared to group P (p < 0.05). Moreover, such treatment also decreased TNF-α and IL-1β levels and NF-κB activity (p < 0.05). In addition, cell necrosis in the hippocampus induced by hepatectomy was also rescued by hydrogen-rich saline. Hydrogen-rich saline can alleviate POCD via inhibiting NF-κB activity in the hippocampus and reducing inflammatory response.
References-https://www.ncbi.nlm.nih.gov/pubmed/26993297
Consumption of molecular hydrogen prevents the stress-induced impairments in hippocampus-dependent learning tasks during chronic physical restraint in mice
ABSTRACT
We have reported that hydrogen (H(2)) acts as an efficient antioxidant by gaseous rapid diffusion. When water saturated with hydrogen (hydrogen water) was placed into the stomach of a rat, hydrogen was detected at several microM level in blood. Because hydrogen gas is unsuitable for continuous consumption, we investigated using mice whether drinking hydrogen water ad libitum, instead of inhaling hydrogen gas, prevents cognitive impairment by reducing oxidative stress. Chronic physical restraint stress to mice enhanced levels of oxidative stress markers, malondialdehyde and 4-hydroxy-2-nonenal, in the brain, and impaired learning and memory, as judged by three different methods: passive avoidance learning, object recognition task, and the Morris water maze. Consumption of hydrogen water ad libitum throughout the whole period suppressed the increase in the oxidative stress markers and prevented cognitive impairment, as judged by all three methods, whereas hydrogen water did not improve cognitive ability when no stress was provided. Neural proliferation in the dentate gyrus of the hippocampus was suppressed by restraint stress, as observed by 5-bromo-2′-deoxyuridine incorporation and Ki-67 immunostaining, proliferation markers. The consumption of hydrogen water ameliorated the reduced proliferation although the mechanistic link between the hydrogen-dependent changes in neurogenesis and cognitive impairments remains unclear. Thus, continuous consumption of hydrogen water reduces oxidative stress in the brain, and prevents the stress-induced decline in learning and memory caused by chronic physical restraint. Hydrogen water may be applicable for preventive use in cognitive or other neuronal disorders.
References-https://www.ncbi.nlm.nih.gov/pubmed/18563058
Drinking Hydrogen Water Ameliorated Cognitive Impairment in Senescence-Accelerated Mice
ABSTRACT
Hydrogen has been reported to have neuron protective effects due to its antioxidant properties, but the effects of hydrogen on cognitive impairment due to senescence-related brain alterations and the underlying mechanisms have not been characterized. In this study, we investigated the efficacies of drinking hydrogen water for prevention of spatial memory decline and age-related brain alterations using senescence-accelerated prone mouse 8 (SAMP8), which exhibits early aging syndromes including declining learning ability and memory. However, treatment with hydrogen water for 30 days prevented age-related declines in cognitive ability seen in SAMP8 as assessed by a water maze test and was associated with increased brain serotonin levels and elevated serum antioxidant activity. In addition, drinking hydrogen water for 18 weeks inhibited neurodegeneration in hippocampus, while marked loss of neurons was noted in control, aged brains of mice receiving regular water. On the basis of our results, hydrogen water merits further investigation for possible therapeutic/preventative use for age-related cognitive disorders.
References-https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2872234/
Hydrogen-rich saline prevents early neurovascular dysfunction resulting from inhibition of oxidative stress in STZ-diabetic rats
ABSTRACT
PURPOSE: Diabetic retinopathy (DR) is characterized by increased oxidative and nitrosative stress, both of which lead to neurotoxicity and vascular permeability. Previous studies on a variety of organs indicate that hydrogen-rich saline not only has considerable antioxidant and anti-inflammatory properties, but also suppresses oxidative stress-induced injury. In the present study, we assessed the effects of hydrogen-rich saline on neurovascular dysfunction and oxidative stress in an animal model (rat) of DR.
MATERIALS AND METHODS: Male Sprague-Dawley rats with streptozotocin (STZ)-induced diabetes mellitus (DM) were injected intraperitoneally with 5 ml/kg hydrogen-saturated (experimental) or plain (control) saline daily for one month. Visual function and blood-retinal barrier (BRB) integrity were evaluated by electroretinography (ERG) and bovine serum albumin (BSA)-fluorescence, respectively. Histological changes in the inner retina were assessed by light microscopy. Biomarkers of oxidative stress, including 4-hydroxynonenal (4-HNE) and 8-hydroxy-2-deoxyguanosine (8-OH-dG), and antioxidant enzymes, including superoxide dismutase, glutathione peroxidase, glutathione reductase and glutathione transferase, were evaluated by ELISA. Synaptophysin and brain-derived neurotrophic factor (BDNF) levels were measured by immunoblotting.
RESULTS: STZ-diabetic rats were marked by clearly reduced b-wave amplitudes and oscillatory potentials, DM-related BRB breakdown and histological changes in the inner retina, all of which were suppressed following treatment with hydrogen-rich saline. Furthermore, hydrogen-rich saline reduced oxidative stress, increased antioxidant enzyme activities and preserved synaptophysin and BDNF levels in the diabetic rat retina.
CONCLUSIONS: Based on its inhibition of oxidative stress and up-regulation of anti-oxidative enzymes, we conclude that hydrogen-rich saline is a potentially valuable therapeutic modality for the treatment of DR.
References-https://www.ncbi.nlm.nih.gov/pubmed/23252792
The role of oxidative stress in degeneration of the neuromuscular junction in amyotrophic lateral sclerosis
ABSTRACT
Amyotrophic lateral sclerosis (ALS) is characterized by the progressive loss of motoneurons and degradation of the neuromuscular junctions (NMJ). Consistent with the dying-back hypothesis of motoneuron degeneration the decline in synaptic function initiates from the presynaptic terminals in ALS. Oxidative stress is a major contributory factor to ALS pathology and affects the presynaptic transmitter releasing machinery.
Indeed, in ALS mouse models nerve terminals are sensitive to reactive oxygen species (ROS) suggesting that oxidative stress, along with compromised mitochondria and increased intracellular Ca(2+) amplifies the presynaptic decline in NMJ. This initial dysfunction is followed by a neurodegeneration induced by inflammatory agents and loss of trophic support. To develop effective therapeutic approaches against ALS, it is important to identify the mechanisms underlying the initial pathological events.
Given the role of oxidative stress in ALS, targeted antioxidant treatments could be a promising therapeutic approach. However, the complex nature of ALS and failure of monotherapies suggest that an antioxidant therapy should be accompanied by anti-inflammatory interventions to enhance the restoration of the redox balance.
References-https://www.ncbi.nlm.nih.gov/pubmed/24860432
Treatment with Hydrogen-Rich Saline Delays Disease Progression in a Mouse Model of Amyotrophic Lateral Sclerosis
ABSTRACT
Amyotrophic lateral sclerosis (ALS) is the most frequent adult-onset motor neuron disease, and accumulating evidence indicates that oxidative mechanisms contribute to ALS pathology, but classical antioxidants have not performed well in clinical trials. The aim of this work was to investigate the effect of treatment with hydrogen molecule on the development of disease in mutant SOD1 G93A transgenic mouse model of ALS. Treatment of mutant SOD1 G93A mice with hydrogen-rich saline (HRS, i.p.) significantly delayed disease onset and prolonged survival, and attenuated loss of motor neurons and suppressed microglial and glial activation. Treatment of mutant SOD1 G93A mice with HRS inhibited the release of mitochondrial apoptogenic factors and the subsequent activation of downstream caspase-3. Furthermore, treatment of mutant SOD1 G93A mice with HRS reduced levels of protein carbonyl and 3-nitrotyrosine, and suppressed formation of reactive oxygen species (ROS), peroxynitrite, and malondialdehyde. Treatment of mutant SOD1 G93A mice with HRS preserved mitochondrial function, marked by restored activities of Complex I and IV, reduced mitochondrial ROS formation and enhanced mitochondrial adenosine triphosphate synthesis. In conclusion, hydrogen molecule may be neuroprotective against ALS, possibly through abating oxidative and nitrosative stress and preserving mitochondrial function.
References-https://www.ncbi.nlm.nih.gov/pubmed/26537817
Electrolyzed hydrogen-saturated water for drinking use elicits an antioxidative effect: a feeding test with rats.
ABSTRACT
A new type of electrolyzed hydrogen-saturated (EHS) water was produced using a water-electrolyzing device equipped with a special cation exchanger. Use of the EHS water for drinking in a feeding test with rats elicited an antioxidative effect. After intraperitoneal injection of 2,2-azobis-amidinopropane dihydrochloride, urinary secretion of 8-hydroxydeoxyguanosine and hepatic formation of peroxidized lipid were significantly lessened in rats which had received the EHS water for one week. These results suggest the possibility that this drinking water shows an effect in reduction of oxidative stress in the body.
Reference – https://www.ncbi.nlm.nih.gov/pubmed/16244454
Extension of the lifespan of Caenorhabditis elegans by the use of electrolyzed reduced water.
ABSTRACT
Electrolyzed reduced water (ERW) has been reported to scavenge intracellular reactive oxygen species (ROS) and improve oxidative stress-related diseases. A new culture method using water medium for Caenorhabditis elegans (C.elegans) was developed in order to elucidate the effects of ERW on the lifespan of nematode. ERW significantly extended the lifespan of C. elegans and alleviated the ROS Level in nematode in water medium, but not in conventional S-medium. These results suggested that the nematode lifespan was elongated at least in part by ROS-scavenging action of ERW.
Reference – https://www.ncbi.nlm.nih.gov/pubmed/20944427
Electrolyzed Reduced Water Prolongs Caenorhabditis elegans’ Lifespan
ABSTRACT
Electrolyzed reduced water (ERW) has been reported to scavenge intracellular reactive oxygen species (ROS) and improve oxidative stress-related diseases. A new culture method using water medium for Caenorhabditis elegans (C.elegans) was developed in order to elucidate the effects of ERW on the lifespan of nematode. ERW significantly extended the lifespan of C. elegans and alleviated the ROS Level in nematode in water medium, but not in conventional S-medium. These results suggested that the nematode lifespan was elongated at least in part by ROS-scavenging action of ERW.
Reference –https://link.springer.com/chapter/10.1007/978-90-481-3892-0_48#page-1
Mechanism of the lifespan extension of Caenorhabditis elegans by electrolyzed reduced water–participation of Pt nanoparticles.
ABSTRACT
Electrolyzed reduced water (ERW) contains a large amount of molecular hydrogen and a small amount of Pt nanoparticles (Pt NPs). We have found that ERW significantly extended the lifespan of Caenorhabditis elegans in a novel culture medium designated Water Medium. In this study, we found that synthetic Pt NPs at ppb levels significantly extended the nematode lifespan and scavenged reactive oxygen species (ROS) in the nematode induced by paraquat treatment. In contrast, a high concentration of dissolved molecular hydrogen had no significant effect on the lifespan of the nematode. These findings suggest that the Pt NPs in ERW, rather than the molecular hydrogen, extend the longevity of the nematode, at least partly by scavenging ROS.
Reference –https://www.ncbi.nlm.nih.gov/pubmed/21737933
Electrolyzed-reduced water scavenges active oxygen species and protects DNA from oxidative damage.
ABSTRACT
Active oxygen species or free radicals are considered to cause extensive oxidative damage to biological macromolecules, which brings about a variety of diseases as well as aging. The ideal scavenger for active oxygen should be ‘active hydrogen’. ‘Active hydrogen’ can be produced in reduced water near the cathode during electrolysis of water. Reduced water exhibits high pH, low dissolved oxygen (DO), extremely high dissolved molecular hydrogen (DH), and extremely negative redox potential (RP) values. Strongly electrolyzed-reduced water, as well as ascorbic acid, (+)-catechin and tannic acid, completely scavenged O.-2 produced by the hypoxanthine-xanthine oxidase (HX-XOD) system in sodium phosphate buffer (pH 7.0). The superoxide dismutase (SOD)-like activity of reduced water is stable at 4 degrees C for over a month and was not lost even after neutralization, repeated freezing and melting, deflation with sonication, vigorous mixing, boiling, repeated filtration, or closed autoclaving, but was lost by opened autoclaving or by closed autoclaving in the presence of tungsten trioxide which efficiently adsorbs active atomic hydrogen. Water bubbled with hydrogen gas exhibited low DO, extremely high DH and extremely low RP values, as does reduced water, but it has no SOD-like activity. These results suggest that the SOD-like activity of reduced water is not due to the dissolved molecular hydrogen but due to the dissolved atomic hydrogen (active hydrogen). Although SOD accumulated H2O2 when added to the HX-XOD system, reduced water decreased the amount of H2O2 produced by XOD. Reduced water, as well as catalase and ascorbic acid, could directly scavenge H2O2. Reduce water suppresses single-strand breakage of DNA b active oxygen species produced by the Cu(II)-catalyzed oxidation of ascorbic acid in a dose-dependent manner, suggesting that reduced water can scavenge not only O2.- and H2O2, but also 1O2 and .OH.
Reference –https://www.ncbi.nlm.nih.gov/pubmed/9169001
Hydrogen Therapy Reduces Oxidative Stress-associated Risks Following Acute and Chronic Exposure to High-altitude Environment.
ABSTRACT
Low pressure, low oxygen concentration, and intense ultraviolet (UV) radiation in high-altitude environments, can cause oxidative stress which can trigger mountain sickness. A recent study demonstrated that hydrogen gas with a good permeability in biological membranes can treat various disorders by exerting its selective anti-oxidation and anti-inflammatory effects, indicating that hydrogen therapy plays a role in scavenging free radicals and in balancing oxidation and anti-oxidation systems of cells. Therefore, we hypothesize that inhaling low-dose hydrogen or drinking hydrogen-saturated water is a novel and simple method to prevent and treat oxidative stress injury caused by low pressure, low oxygen concentration and intense UV radiation in plateaus, thus reducing the risk of mountain sickness.
Reference –https://www.ncbi.nlm.nih.gov/pubmed/25800452
Administration of hydrogen-rich saline protects mice from lethal acute graft-versus-host disease (aGVHD).
ABSTRACT
BACKGROUND:
Allogeneic hematopoietic stem cell transplantation is a potentially curative therapy for many malignant and nonmalignant hematologic diseases. However, acute graft-versus-host disease (aGVHD) is a lethal complication of hematopoietic stem cell transplantation, which limits its application. Cytokines such as tumor necrosis factor-α and interleukin-6 play an extremely important role in the formation and development of aGVHD. Reactive oxygen species, such as hydroxyl radicals, also play an important role in the formation and development of aGVHD. In recent years, hydrogen was reported to have an ability to inhibit the levels of cytokines, such as tumor necrosis factor and interleukin-6 in vivo, and it also has a strong selective free radical-scavenging ability. Therefore, we hypothesized that hydrogen may have therapeutic effects on aGVHD.
METHODS:
To determine whether hydrogen could protect mice from lethal GVHD in a major histocompatibility complex-incompatible murine bone marrow transplantation (BMT) model, survival rates of mice were calculated and leukocyte counts were also determined after BMT. We also examined serum cytokine levels and scored clinical signs of GVHD mice after BMT.
RESULTS AND CONCLUSION:
This article demonstrated that the administration of hydrogen-rich saline increased the survival rate and clinical score of aGVHD mice. Administration of hydrogen-rich saline after transplantation also promoted the recovery of white blood cells of aGVHD mice. However, there was no report on the therapeutic effects of hydrogen on aGVHD. It is suggested that hydrogen has a potential as an effective and safe therapeutic agent on aGVHD.
Reference –https://www.ncbi.nlm.nih.gov/pubmed/23503500
ONOOH does not react with H2: Potential beneficial effects of H2 as an antioxidant by selective reaction with hydroxyl radicals and peroxynitrite.
ABSTRACT
H2 has been suggested to act as an antioxidant when administered just before the reperfusion phase of induced oxidative stress. These effects have been reported, for example, for the heart, brain, and liver. It is hypothesized that this beneficial effect may be due to selective scavenging of HO(⋅) and ONOOH by H2. The reaction of H2 with HO(⋅) has been studied by pulse radiolysis in the past and is too slow to be physiologically relevant, not to mention that the reaction yields the reactive H(⋅) radical. We therefore investigated whether H2 reacts with ONOOH and whether the presence of H2 influences the yield of nitration of tyrosine by ONOOH. With only negative results, we entertained the notion that H2 may possibly exert its beneficial effects by reducing Fe(III) centers, oxidized during oxidative stress. However, neither hemes nor iron-sulfur clusters were reduced.
Reference – https://www.ncbi.nlm.nih.gov/pubmed/25086438
Electrolyzed-reduced water increases resistance to oxidative stress, fertility, and lifespan via insulin/IGF-1-like signal in C. elegans.
ABSTRACT
Electrolyzed-reduced water (ERW) scavenges reactive oxygen species and is a powerful anti-oxidant. A positive correlation between oxidative stress and aging has been proved in many model organisms. In Caenorhabditis elegans, many long-lived mutants showed reduced fertility as a trade off against longevity phenotype. We aimed to study the effect of ERW on oxidative stress, fertility and lifespan of C. elegans. We also investigated the genetic pathway involved in the effect of ERW on resistance to oxidative stress and lifespan. We compared lifespan and fertility of worms in media prepared with distilled water and ERW. ERW significantly extended lifespan and increased the number of progeny produced. Then the effect of ERW on resistance to oxidative stress and lifespan of long-lived mutants was determined. ERW increased resistance to oxidative stress and lifespan of eat-2, a genetic model of dietary restriction, but had no effect on those of age-1, which is involved in insulin/insulin-like growth factor (IGF)-1-like signal. In addition, knockdown of daf-16, the downstream mediator of insulin/IGF-1-like signal, completely prevented the effect of ERW on lifespan. These findings suggest that ERW can extend lifespan without accompanying reduced fertility and modulate resistance to oxidative stress and lifespan via insulin/IGF-1-like signal in C. elegans.
Reference – https://www.ncbi.nlm.nih.gov/pubmed/23959012
The evolution of molecular hydrogen: a noteworthy potential therapy with clinical significance
ABSTRACT
Studies on molecular hydrogen have evolved tremendously from its humble beginnings and have continued to change throughout the years. Hydrogen is extremely unique since it has the capability to act at the cellular level. Hydrogen is qualified to cross the blood brain barrier, to enter the mitochondria, and even has the ability to trans-locate to the nucleus under certain conditions.
Once in these ideal locations of the cell, previous studies have shown that hydrogen exerts antioxidant, anti-apoptotic, anti-inflammatory, and cytoprotective properties that are beneficial to the cell. Hydrogen is most commonly applied as a gas, water, saline, and can be applied in a variety of other mediums.
There are also few side effects involving hydrogen, thus making hydrogen a perfect medical gas candidate for the convention of novel therapeutic strategies against cardiovascular, cerebrovascular, cancer, metabolic, and respiratory diseases and disorders. Although hydrogen appears to be faultless at times, there still are several deficiencies or snares that need to be investigated by future studies. This review article seeks to delve and comprehensively analyze the research and experiments that alludes to molecular hydrogen being a novel therapeutic treatment that medicine desperately needs.
Reference-https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660246/
Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome-an open label pilot stud
ABSTRACT
Metabolic syndrome is characterized by cardiometabolic risk factors that include obesity, insulin resistance, hypertension and dyslipidemia. Oxidative stress is known to play a major role in the pathogenesis of metabolic syndrome. The objective of this study was to examine the effectiveness of hydrogen rich water (1.5-2 L/day) in an open label, 8-week study on 20 subjects with potential metabolic syndrome. Hydrogen rich water was produced, by placing a metallic magnesium stick into drinking water (hydrogen concentration; 0.55-0.65 mM), by the following chemical reaction; Mg + 2H(2)O –> Mg (OH)(2) + H(2). The consumption of hydrogen rich water for 8 weeks resulted in a 39% increase (p<0.05) in antioxidant enzyme superoxide dismutase (SOD) and a 43% decrease (p<0.05) in thiobarbituric acid reactive substances (TBARS) in urine. Further, subjects demonstrated an 8% increase in high density lipoprotein (HDL)-cholesterol and a 13% decrease in total cholesterol/HDL-cholesterol from baseline to week 4. There was no change in fasting glucose levels during the 8 week study. In conclusion, drinking hydrogen rich water represents a potentially novel therapeutic and preventive strategy for metabolic syndrome. The portable magnesium stick was a safe, easy and effective method of delivering hydrogen rich water for daily consumption by participants in the study.
Reference–https://www.ncbi.nlm.nih.gov/pubmed/20216947/
Molecular hydrogen stabilizes atherosclerotic plaque in low-density lipoprotein receptor-knockout mice
ABSTRACT
Hydrogen (H(2)) attenuates the development of atherosclerosis in mouse models. We aimed to examine the effects of H(2) on atherosclerotic plaque stability. Low-density lipoprotein receptor-knockout (LDLR(-/-)) mice fed an atherogenic diet were dosed daily with H(2) and/or simvastatin. In vitro studies were carried out in an oxidized-LDL (ox-LDL)-stimulated macrophage-derived foam cell model treated with or without H(2). H(2) or simvastatin significantly enhanced plaque stability by increasing levels of collagen, as well as reducing macrophage and lipid levels in plaques. The decreased numbers of dendritic cells and increased numbers of regulatory T cells in plaques further supported the stabilizing effect of H(2) or simvastatin. Moreover, H(2) treatment decreased serum ox-LDL level and apoptosis in plaques with concomitant inhibition of endoplasmic reticulum stress (ERS) and reduction of reactive oxygen species (ROS) accumulation in the aorta. In vitro, like the ERS inhibitor 4-phenylbutyric acid, H(2) inhibited ox-LDL- or tunicamycin (an ERS inducer)-induced ERS response and cell apoptosis. In addition, like the ROS scavenger N-acetylcysteine, H(2) inhibited ox-LDL- or Cu(2+) (an ROS inducer)-induced reduction in cell viability and increase in cellular ROS. Also, H(2) increased Nrf2 (NF-E2-related factor-2, an important factor in antioxidant signaling) activation and Nrf2 small interfering RNA abolished the protective effect of H(2) on ox-LDL-induced cellular ROS production. The inhibitory effects of H(2) on the apoptosis of macrophage-derived foam cells, which take effect by suppressing the activation of the ERS pathway and by activating the Nrf2 antioxidant pathway, might lead to an improvement in atherosclerotic plaque stability.
Reference– https://www.ncbi.nlm.nih.gov/pubmed/26117323
Molecular hydrogen stimulates the gene expression of transcriptional coactivator PGC-1α to enhance fatty acid metabolism
ABSTRACT
We previously reported that molecular hydrogen (H2) acts as a novel antioxidant to exhibit multiple functions. Moreover, long-term drinking of H2-water (water infused with H2) enhanced energy expenditure to improve obesity and diabetes in db/db mice accompanied by the increased expression of fibroblast growth factor 21 (FGF21) by an unknown mechanism. H2 was ingested by drinking of H2-water or by oral administration of an H2-producing material, MgH2. The comprehensive gene expression profile in the liver of db/db mice was analyzed by DNA microarray. The molecular mechanisms underlying the gene expression profile was investigated using cultured HepG2 cells. Moreover, the effects on lifespan of drinking H2-water were examined using wild-type mice that were fed a fatty diet. Pathway analyses based on comprehensive gene expression revealed the increased expression of various genes involved in fatty acid and steroid metabolism. As a transcription pathway, the PPARα signaling pathway was identified to upregulate their genes by ingesting H2. As an early event, the gene expression of PGC-1α was transiently increased, followed by increased expression of FGF21. The expression of PGC-1α might be regulated indirectly through sequential regulation by H2, 4-hydroxy-2-nonenal, and Akt/FoxO1 signaling, as suggested in cultured cell experiments. In wild-type mice fed the fatty diet, H2-water improved the level of plasma triglycerides and extended their average of lifespan. H2 induces expression of the PGC-1α gene, followed by stimulation of the PPARα pathway that regulates FGF21, and the fatty acid and steroid metabolism.
Reference– https://www.nature.com/articles/npjamd20168
Molecular hydrogen improves obesity and diabetes by inducing hepatic FGF21 and stimulating energy metabolism in db/db mice
ABSTRACT
Recent extensive studies have revealed that molecular hydrogen (H(2)) has great potential for improving oxidative stress-related diseases by inhaling H(2) gas, injecting saline with dissolved H(2), or drinking water with dissolved H(2) (H(2)-water); however, little is known about the dynamic movement of H(2) in a body. First, we show that hepatic glycogen accumulates H(2) after oral administration of H(2)-water, explaining why consumption of even a small amount of H(2) over a short span time efficiently improves various disease models. This finding was supported by an in vitro experiment in which glycogen solution maintained H(2). Next, we examined the benefit of ad libitum drinking H(2)-water to type 2 diabetes using db/db obesity model mice lacking the functional leptin receptor. Drinking H(2)-water reduced hepatic oxidative stress, and significantly alleviated fatty liver in db/db mice as well as high fat-diet-induced fatty liver in wild-type mice. Long-term drinking H(2)-water significantly controlled fat and body weights, despite no increase in consumption of diet and water. Moreover, drinking H(2)-water decreased levels of plasma glucose, insulin, and triglyceride, the effect of which on hyperglycemia was similar to diet restriction. To examine how drinking H(2)-water improves obesity and metabolic parameters at the molecular level, we examined gene-expression profiles, and found enhanced expression of a hepatic hormone, fibroblast growth factor 21 (FGF21), which functions to enhance fatty acid and glucose expenditure. Indeed, H(2) stimulated energy metabolism as measured by oxygen consumption. The present results suggest the potential benefit of H(2) in improving obesity, diabetes, and metabolic syndrome.
Reference–https://www.ncbi.nlm.nih.gov/pubmed/21293445
Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance
ABSTRACT
Oxidative stress is recognized widely as being associated with various disorders including diabetes, hypertension, and atherosclerosis. It is well established that hydrogen has a reducing action. We therefore investigated the effects of hydrogen-rich water intake on lipid and glucose metabolism in patients with either type 2 diabetes mellitus (T2DM) or impaired glucose tolerance (IGT). We performed a randomized, double-blind, placebo-controlled, crossover study in 30 patients with T2DM controlled by diet and exercise therapy and 6 patients with IGT. The patients consumed either 900 mL/d of hydrogen-rich pure water or 900 mL of placebo pure water for 8 weeks, with a 12-week washout period. Several biomarkers of oxidative stress, insulin resistance, and glucose metabolism, assessed by an oral glucose tolerance test, were evaluated at baseline and at 8 weeks. Intake of hydrogen-rich water was associated with significant decreases in the levels of modified low-density lipoprotein (LDL) cholesterol (ie, modifications that increase the net negative charge of LDL), small dense LDL, and urinary 8-isoprostanes by 15.5% (P < .01), 5.7% (P < .05), and 6.6% (P < .05), respectively. Hydrogen-rich water intake was also associated with a trend of decreased serum concentrations of oxidized LDL and free fatty acids, and increased plasma levels of adiponectin and extracellular-superoxide dismutase. In 4 of 6 patients with IGT, intake of hydrogen-rich water normalized the oral glucose tolerance test. In conclusion, these results suggest that supplementation with hydrogen-rich water may have a beneficial role in prevention of T2DM and insulin resistance.
Reference–https://www.ncbi.nlm.nih.gov/pubmed/19083400
Molecular hydrogen attenuates fatty acid uptake and lipid accumulation through down regulating CD36 expression in HepG2 Cells
ABSTRACT
BACKGROUND:
There is accumulating evidence that obesity is closely associated with an impaired free fatty acid metabolism as well as with insulin resistance and inflammation. Excessive fatty acid uptake mediated by fatty acid translocase CD36 plays an important role in hepatic steatosis. Molecular hydrogen has been shown to attenuate oxidative stress and improve lipid, glucose and energy metabolism in patients and animal models of hepatic steatosis and atherosclerosis, but the underlying molecular mechanisms remain largely unknown.
METHODS:
Human hepatoma HepG2 cells were exposed to palmitate-BSA complex after treatment with or without hydrogen for 24 h. The fatty acid uptake was measured by using spectrofluorometry and the lipid content was detected by Oil Red O staining. JNK phosphorylation and CD36 expression were analyzed by Western blot and real-time PCR analyses.
RESULTS:
Pre-treatment with hydrogen reduced fatty acid uptake and lipid accumulation after palmitate overload in HepG2 cells, which was associated with inhibition of JNK activation. Hydrogen treatment did not alter CD36 mRNA expression but reduced CD36 protein expression.
CONCLUSION:
Hydrogen inhibits fatty acid uptake and lipid accumulation through the down regulation of CD36 at the protein level in hepatic cultured cells, providing insights into the molecular mechanism underlying the hydrogen effects in vivo on lipid metabolism disorders.
Reference–https://www.ncbi.nlm.nih.gov/pubmed/23448206
Oxidative stress in acne vulgaris: an important therapeutic target Addressing Free Radical Oxidation in Acne Vulgari
Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in mice Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in mice Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury
Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord Injury Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancer Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancer Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancer Top of Form
Oxidative stress in acne vulgaris: an important therapeutic target
ABSTRACT
Objective: There has been an increasing focus on the extent to which oxidative stress is involved in the pathophysiology of acne. The aim of this study is to investigate the existence of oxidative stress and inflammatory marker IL-8 in patients with acne vulgaris, and the role of oxidative stress as a therapeutic target in the treatment of acne vulgaris.
Methods:
A randomized prospective clinical trial was carried out on 56 patients of both sexes with age range of 14-35 years who attend to outpatient clinic in Al-Hussein Teaching Hospital-Kerbalaa -Iraq over a period from December 2011 to May 2012, all patients examined clinically by dermatologist and classified according to disease severity. Serum levels of glutathione (GSH), malondialdehyde (MDA) and interleukine -8 (IL-8) in the acne patients were measured by using ready- for- use Elisa kits, and compared to that of 28 healthy volunteers. Results: The results of the serum level analysis of MDA for the acne patients (expressed as the mean± standard deviation) was highly significant (P value ≤ 0.001) higher than that of healthy volunteers, while serum level of GSH was highly significant (P value ≤ 0.001) lower in acne patients compared to healthy volunteers; there is a significant difference (P value ≤ 0.05) found in serum levels of IL-8 between the acne patients and the healthy volunteers.
Conclusions: The results obtained in this study clearly showed the existence of oxidative stress in patients with acne vulgaris, and that oxidative stress along with inflammation play a critical role in acne pathogenesis; furthermore, oxidative stress in acne patients may represents a potential therapeutic target and interference with antioxidant is a rationale choice.
References-https://www.ejmanager.com/mnstemps/66/66-1345206572.pdf
Hydrogen-Rich Saline Attenuates Lipopolysaccharide-Induced Heart Dysfunction by Restoring Fatty Acid Oxidation in Rats by Mitigating C-Jun N-Terminal Kinase Activation
ABSTRACT
Sepsis is common in intensive care units (ICU) and is associated with high mortality. Cardiac dysfunction complicating sepsis is one of the most important causes of this mortality. This dysfunction is due to myocardial inflammation and reduced production of energy by the heart. A number of studies have shown that hydrogen-rich saline (HRS) has a beneficial effect on sepsis. Therefore, we tested whether HRS prevents cardiac dysfunction by increasing cardiac energy. Four groups of rats received intraperitoneal injections of one of the following solutions: normal saline (NS), HRS, lipopolysaccharide (LPS), and LPS plus HRS. Cardiac function was measured by echocardiography 8 h after the injections. Gene and protein expression related to fatty acid oxidation (FAO) were measured by quantitative polymerase chain reaction (PCR) and Western blot analysis. The injection of LPS compromised heart function through decreased fractional shortening (FS) and increased left ventricular diameter (LVD). The addition of HRS increased FS, palmitate triphosphate, and the ratio of phosphocreatinine (PCr) to adenosine triphosphate (ATP) as well as decreasing LVD. The LPS challenge reduced the expression of genes related to FAO, including perioxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), perioxisome proliferator-activated receptor alpha (PPARα), Estrogen-related receptor alpha (ERRα), and their downstream targets, in mRNA and protein level, which were attenuated by HRS. However, HRS had little effect on glucose metabolism. Furthermore, HRS inhibited c-Jun N-terminal kinase (JNK) activation in the rat heart. Inhibition of JNK by HRS showed beneficial effects on LPS-challenged rats, at least in part, by restoring cardiac FAO.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/26565704
Chronic hydrogen-rich saline treatment attenuates vascular dysfunction in spontaneous hypertensive rats
ABSTRACT
In hypertensive patients, increased oxidative stress is thought to be one important cause of vascular dysfunction. Recently, it has been suggested that hydrogen exerts a therapeutic antioxidant activity by selectively reducing hydroxyl radical and peroxynitrite, the most cytotoxic chemicals of reactive oxygen species (ROS). Herein, we investigated the protective effect of chronic treatment with hydrogen-rich saline (HRS) against vascular dysfunction in SHR and the underlying mechanism. The 8-week-old spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto rats (WKY) were randomized into HRS-treated (6ml/kg/day for 3 months, i.p.) and vehicle treated group. Treatment with HRS ameliorated vascular dysfunction including aortic hypertrophy and endothelial function in SHR. Treatment with HRS had no significant effect on blood pressure, but it significantly improved baroreflex function in SHR. Treatment with HRS abated oxidative stress, restored antioxidant enzymes including superoxide dismutase, glutathione peroxidase, and catalase, and suppressed NADPH oxidase. Furthermore, treatment with HRS depressed pro-inflammatory cytokines expression including IL-6 and IL-1β and suppressed NF-κB activation, restored mitochondrial function including ATP formation and membrane integrity. In addition, although treatment with HRS had no significant effect on nitric oxide amount in circulating or aorta, it suppressed endothelial nitric oxide synthase expression and upregulated dimethylarginine dimethylaminohydrolase 2 expression in SHR. In conclusion, treatment with HRS alleviates vascular dysfunction through abating oxidative stress, restoring baroreflex function, suppressing inflammation, preserving mitochondrial function, and enhancing nitric oxide bioavailability.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/22342731
Effect of Treadmill Exercise and Hydrogen-rich Water Intake on Serum Oxidative and Anti-oxidative Metabolites in Serum of Thoroughbred Horses
ABSTRACT
The present study aimed to clarify changes of oxidative stress and antioxidative functions in treadmill-exercised Thoroughbred horses (n=5, 3 to 7 years old), using recently developed techniques for measurement of serum d-ROMs for oxidative stress, and BAP for antioxidative markers. Also, the effect of nasogastric administration of hydrogen-rich water (HW) or placebo water preceding the treadmill exercise on these parameters was examined. Each horse was subjected to a maximum level of treadmill exercise in which the horses were exhausted at an average speed of 13.2 ± 0.84 m/sec.
Blood samples were taken 4 times, immediately before the intake of HW or placebo water at 30 min preceding the treadmill exercise, immediately before the exercise (pre-exercise), immediately after the exercise (post-exercise) and at 30 min following the exercise. In all horses, both d-ROMs and BAP values significantly increased at post-exercise. The increase in d-ROMs tended to be lower in the HW trial, as compared to the placebo trial at pre-exercise.
The increase in BAP was considerable at approximately 150% of the pre-exercise values in both the HW and placebo treatment trials. The BAP/d-ROMs ratio was significantly elevated at post-exercise in both treatment trials, while a significant elevation was also observed at pre-exercise in the HW trial. BAP, d-ROM, and the BAP/d-ROM ratio tended to decline at 30 min after the exercise, except BAP and BAP/d-ROMs in the placebo trial. These results demonstrate that the marked elevation of oxidative stress and anitioxidative functions occurred simultaneously in the intensively exercised horses, and suggest a possibility that HW has some antioxidative efficacy.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/24833996
Molecular hydrogen in sports medicine: new therapeutic perspectives
ABSTRACT
In the past 2 decades, molecular hydrogen emerged as a novel therapeutic agent, with antioxidant, anti-inflammatory and anti-apoptotic effects demonstrated in plethora of animal disease models and human studies. Beneficial effects of molecular hydrogen in clinical environment are observed especially in oxidative stress-mediated diseases, such as diabetes mellitus, brain stem infarction, rheumatoid arthritis, or neurodegenerative diseases. A number of more recent studies have reported that molecular hydrogen affects cell signal transduction and acts as an alkalizing agent, with these newly identified mechanisms of action having the potential to widen its application in clinical medicine even further. In particular, hydrogen therapy may be an effective and specific innovative treatment for exercise-induced oxidative stress and sports injury, with potential for the improvement of exercise performance. This review will summarize recent research findings regarding the clinical aspects of molecular hydrogen use, emphasizing its application in the field of sports medicine.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/25525953
Hydrogen-rich water affected blood alkalinity in physically active men.
ABSTRACT
Possible appliance of effective and safe alkalizing agent in the treatment of metabolic acidosis could be of particular interest to humans experiencing an increase in plasma acidity, such as exercise-induced acidosis. In the present study we tested the hypothesis that the daily oral intake of 2L of hydrogen-rich water (HRW) for 14 days would increase arterial blood alkalinity at baseline and post-exercise as compared with the placebo. This study was a randomized, double blind, placebo-controlled trial involving 52 presumably healthy physically active male volunteers. Twenty-six participants received HRW and 26 a placebo (tap water) for 14 days. Arterial blood pH, partial pressure for carbon dioxide (pCO2), and bicarbonates were measured at baseline and postexercise at the start (day 0) and at the end of the intervention period (day 14). Intake of HRW significantly increased fasting arterial blood pH by 0.04 (95% confidence interval; 0.01 – 0.08; p < 0.001), and postexercise pH by 0.07 (95% confidence interval; 0.01 – 0.10; p = 0.03) after 14 days of intervention. Fasting bicarbonates were significantly higher in the HRW trial after the administration regimen as compared with the preadministration (30.5 ± 1.9 mEq/L vs. 28.3 ± 2.3 mEq/L; p < 0.0001). No volunteers withdrew before the end of the study, and no participant reported any vexatious side effects of supplementation. These results support the hypothesis that HRW administration is safe and may have an alkalizing effect in young physically active men.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/24392771
DRINKS WITH ALKALINE NEGATIVE OXIDATIVE REDUCTION POTENTIAL IMPROVE EXERCISE PERFORMANCE IN PHYSICALLY ACTIVE MEN AND WOMEN: DOUBLE-BLIND, RANDOMIZED,PLACEBO-CONTROLLED, CROSS-OVER TRIAL OF EFFICACY AND SAFETY
ABSTRACT
In the current study we tested the hypothesis that an acute (7 days) intake of an alkaline negative oxidative reduction potential formulation (NORP) drink would reduce the rate of blood lactate accumulation during and after exercise, increase time to exhaustion, increase serum buffering capacity and not increase prevalence of adverse effects as compared to the control drink. Eleven participants (9 men and 2 women) met the criteria to take part in the study. Participants were randomized in a double-blind, cross-over design to receive the control and the NORP drinks within two single-week periods to study the efficacy of the NORP drink (at a dose of 1 L per day by oral administration). The NORP drink was supplied in bottles containing 2 g NORP, 6 g sucrose, 1-2 mg sodium per dose. The control drink was identically supplied and formulated except that it contained no NORP. Exercise testing was performed using a treadmill based ramp protocol. Blood glucose or total antioxidant capacity were not affected by supplementation (p > 0.05) while serum bicarbonates were significantly higher after the NORP trial (p < 0.05). Critical HR at the velocity of 8.1 mph during the test was significantly lower in NORP as compared to the control drink trial (p < 0.05). Blood lactate sampled at velocity 8.1 mph during the test was significantly lower in the NORP group (p < 0.05). No athletes reported any vexatious side effects of supplementation. It seems that NORP supplementation could have a beneficial effect on human performance during maximal exercise.
Reference https://www.researchgate.net/publication/225183451_DRINKS_WITH_ALKALINE_NEGATIVE_OXIDATIVE_REDUCTION_POTENTIAL_IMPROVE_EXERCISE_PERFORMANCE_IN_PHYSICALLY_ACTIVE_MEN_AND_WOMEN_DOUBLE-BLIND_RANDOMIZEDPLACEBO-CONTROLLED_CROSS-OVER_TRIAL_OF_EFFICACY_AND_S
Recent Progress Toward Hydrogen Medicine: Potential of Molecular Hydrogen for Preventive and Therapeutic Applications
ABSTRACT
Persistent oxidative stress is one of the major causes of most lifestyle-related diseases, cancer and the aging process. Acute oxidative stress directly causes serious damage to tissues. Despite the clinical importance of oxidative damage, antioxidants have been of limited therapeutic success. We have proposed that molecular hydrogen (H2) has potential as a “novel” antioxidant in preventive and therapeutic applications [Ohsawa et al., Nat Med. 2007: 13; 688-94]. H2 has a number of advantages as a potential antioxidant: H2 rapidly diffuses into tissues and cells, and it is mild enough neither to disturb metabolic redox reactions nor to affect reactive oxygen species (ROS) that function in cell signaling, thereby, there should be little adverse effects of consuming H2. There are several methods to ingest or consume H2, including inhaling hydrogen gas, drinking H2-dissolved water (hydrogen water), taking a hydrogen bath, injecting H2-dissolved saline (hydrogen saline), dropping hydrogen saline onto the eye, and increasing the production of intestinal H2 by bacteria. Since the publication of the first H2 paper in Nature Medicine in 2007, the biological effects of H2 have been confirmed by the publication of more than 38 diseases, physiological states and clinical tests in leading biological/medical journals, and several groups have started clinical examinations. Moreover, H2 shows not only effects against oxidative stress, but also various anti-inflammatory and anti-allergic effects. H2 regulates various gene expressions and protein-phosphorylations, though the molecular mechanisms underlying the marked effects of very small amounts of H2 remain elusive.
Reference-https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257754/
Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals
ABSTRACT
Acute oxidative stress induced by ischemia-reperfusion or inflammation causes serious damage to tissues, and persistent oxidative stress is accepted as one of the causes of many common diseases including cancer. We show here that hydrogen (H(2)) has potential as an antioxidant in preventive and therapeutic applications. We induced acute oxidative stress in cultured cells by three independent methods. H(2) selectively reduced the hydroxyl radical, the most cytotoxic of reactive oxygen species (ROS), and effectively protected cells; however, H(2) did not react with other ROS, which possess physiological roles. We used an acute rat model in which oxidative stress damage was induced in the brain by focal ischemia and reperfusion. The inhalation of H(2) gas markedly suppressed brain injury by buffering the effects of oxidative stress. Thus H(2) can be used as an effective antioxidant therapy; owing to its ability to rapidly diffuse across membranes, it can reach and react with cytotoxic ROS and thus protect against oxidative damage.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/17486089
Hydrogen‐supplemented drinking water protects cardiac allografts from inflammation‐associated deterioration
ABSTRACT
Recent evidence suggests that molecular hydrogen has therapeutic value for disease states that involve inflammation. We hypothesized that drinking hydrogen‐rich water (HW) daily would protect cardiac and aortic allograft recipients from inflammation‐associated deterioration. Heterotopic heart transplantation with short‐course tacrolimus immunosuppression and orthotopic aortic transplantation were performed in allogeneic rat strains. HW was generated either by bubbling hydrogen gas through tap water (Bu‐HW) or via chemical reaction using a magnesium 2H + stick [Mg2O → Mg (OH)2H + 2] immersed in tap water (Mg‐HW). Recipients were given either regular water (RW), Mg‐HW, Bu‐HW, or Mg‐HW that had been subsequently degassed (DW). Graft survival was assessed by daily palpation for a heartbeat. Drinking Mg‐HW or Bu‐HW was remarkably effective in prolonging heart graft survival and reducing intimal hyperplasia in transplanted aortas as compared with grafts treated with RW or DW. Furthermore, T cell proliferation was significantly inhibited in the presence of hydrogen in vitro, accompanied by less production of interleukin‐2 and interferon‐γ. Hydrogen treatment was also associated with increased graft ATP levels and increased activity of the enzymes in mitochondrial respiratory chain. Drinking HW prolongs survival of cardiac allografts and reduces intimal hyperplasia of aortic allografts.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/21226992
Hydrogen as a selective antioxidant: a review of clinical and experimental studies
ABSTRACT
Oxidative stress is implicated in the pathogenesis of many diseases; however, currently used antioxidants have a high toxicity that constrains administration to a narrow window of therapeutic dosage. There is a clear need for more effective and safer antioxidants. Diatomic hydrogen (H(2)) was proposed as a novel antioxidant that selectively reduces levels of toxic reactive-oxygen species. Recently, many studies have reported that H(2) (inhaled or orally ingested, typically as approximately 0.8 mM H(2)-saturated water), can exert beneficial effects in diverse animal models of ischaemia-reperfusion injury, and inflammatory and neurological disease. In the clinic, oral administration of H(2)-saturated water is reported to improve lipid and glucose metabolism in subjects with diabetes or impaired glucose tolerance; promising results have also been obtained in reducing inflammation in haemodialysis patients and treating metabolic syndrome. These studies suggest H(2) has selective antioxidant properties, and can exert antiapoptotic, antiinflammatory and antiallergy effects. This review summarizes recent research findings and mechanisms concerning the therapeutic potential of H(2).
Reference-https://www.ncbi.nlm.nih.gov/pubmed/21226992
Hydrogen water consumption prevents osteopenia in ovariectomized rats
ABSTRACT
BACKGROUND AND PURPOSE: Accumulating evidence indicates an important role of oxidative stress in the progression of osteoporosis. Recently, it was demonstrated that hydrogen gas, as a novel antioxidant, could selectively reduce hydroxyl radicals and peroxynitrite anion to exert potent therapeutic antioxidant activity. The aim of the present work was to investigate the effect of hydrogen water (HW) consumption on ovariectomy-induced osteoporosis.
EXPERIMENTAL APPROACH: Ovariectomized rats were fed with HW (1.3 ± 0.2 mg·L⁻¹) for 3 months. Then, blood was collected and femur and vertebrae were removed for evaluation of the effect of HW on bone.
KEY RESULTS: HW consumption in ovariectomized rats had no significant effect on oestrogen production, but prevented the reduction of bone mass including bone mineral content and bone mineral density in femur and vertebrae, and preserved mechanical strength including ultimate load, stiffness, and energy, and bone structure including trabecular bone volume fraction, trabecular number, and trabecular thickness in femur, and preserved mechanical strength including ultimate load and stiffness, and bone structure including trabecular bone volume fraction and trabecular number in vertebrae. In addition, treatment with HW abated oxidative stress and suppressed IL-6 and TNF-α mRNA expressions in femur of ovariectomized rats; treatment with HW increased femur endothelial NOS activity and enhanced circulating NO level in ovariectomized rats.
CONCLUSIONS AND IMPLICATIONS: HW consumption prevents osteopenia in ovariectomized rats possibly through the ablation of oxidative stress induced by oestrogen withdrawal.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/23121335
Treatment with hydrogen molecules prevents RANKL-induced osteoclast differentiation associated with inhibition of ROS formation and inactivation of MAPK, AKT and NF-kappa B pathways in murine RAW264.7 cells
ABSTRACT
The bone protective effects of the hydrogen molecule (H2) have been demonstrated in several osteoporosis models while the underlying molecular mechanism has remained unclear. Osteoclast differentiation is an important factor related to the pathogenesis of bone-loss related diseases. In this work, we evaluated the effects of incubation with H2 on receptor activator of NFκB ligand (RANKL)-induced osteoclast differentiation. We found that treatment with H2 prevented RANKL-induced osteoclast differentiation in RAW264.7 cells and BMMs. Treatment with H2 inhibits the ability to form resorption pits of BMMs stimulated by RANKL. Treatment with H2 reduced mRNA levels of osteoclast-specific markers including tartrate resistant acid phosphatase, calcitonin receptor, cathepsin K, metalloproteinase-9, carbonic anhydrase typeII, and vacuolar-type H(+)-ATPase. Treatment with H2 decreased intracellular reactive oxygen species (ROS) formation, suppressed NADPH oxidase activity, down-regulated Rac1 activity and Nox1 expression, reduced mitochondrial ROS formation, and enhanced nuclear factor E2-related factor 2 nuclear translocation and heme oxygenase-1 activity. In addition, treatment with H2 suppressed RANKL-induced expression of nuclear factor of activated T cells c1 and c-Fos. Furthermore, treatment with H2 suppressed NF-κB activation and reduced phosphorylation of p38, extracellular signal-regulated kinase, c-Jun-N-terminal kinase, and protein kinases B (AKT) stimulated with RANKL. In conclusion, hydrogen molecules prevented RANKL-induced osteoclast differentiation associated with inhibition of reactive oxygen species formation and inactivation of NF-κB, mitogen-activated protein kinase and AKT pathways.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/24196871
Hydrogen-rich water improves neurological functional recovery in experimental autoimmune encephalomyelitis mice
ABSTRACT
Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS). The high costs, inconvenient administration, and side effects of current Food and Drug Administration (FDA)-approved drugs often lead to poor adherence to the long-term treatment of MS. Molecular hydrogen (H2) has been reported to exhibit anti-oxidant, anti-apoptotic, anti-inflammatory, anti-allergy, and anti-cancer effects. In the present study, we explored the prophylactic and therapeutic effects of hydrogen-rich water (HRW) on the progress of experimental autoimmune encephalomyelitis (EAE), the animal model for MS. We found that prophylactic administration of both 0.36mM and 0.89mM HRW was able to delay EAE onset and reduce maximum clinical scores. Moreover, 0.89mM HRW also reduced disease severity, CNS infiltration, and demyelination when administered after the onset of disease. Furthermore, HRW treatment prevented infiltration of CD4(+) T lymphocytes into the CNS and inhibited Th17 cell development without affecting Th1 cell populations. Because HRW is non-toxic, inexpensive, easily administered, and can readily cross the blood-brain barrier, our experiments suggest that HRW may have great potential in the treatment of MS.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/27138092
Therapeutic effects of hydrogen-rich solution on aplastic anemia in vivo
ABSTRACT
BACKGROUND:
Aplasitc anemia (AA) is a bone marrow failure syndrome characterized by an immune-mediated destruction of hematopoietic stem cells. Though clinical symptoms could be ameliorated by bone marrow transplantation and/or immunosuppressive therapy, frequent recurrence and especially evolution of clonal hematologic diseases remains problematic clinically. Cytokines such as interferon-γ (INF-γ), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) secreted by autologous T cells are closely related with the development of AA. Hydrogen-rich solution was reported to inhibit the levels of cytokines including INF-γ, TNF-α and IL-6 in vivo in recent studies. This study was to investigate the potential therapeutic effects of hydrogen-rich solution on AA in vivo.
METHODS:
AA model was determined in vivo by mice and body weights of the mice were used as the basic physiological index. Peripheral blood cells were calculated to evaluate the hematologic recovery degree. Bone marrow nucleated cells (BMNCs), tissue histology, as well as CFU-S and CFU-GM forming units were used to evaluate the recovery of bone marrow microenvironment. The ratio of CD4(+) and CD8(+) cells were examined along with cytokine levels in serum to determine the efficacy of H2-rich solution on the affected immunological functions.
RESULTS: Body weight and number of peripheral blood cells were significantly improved for mice in the H2-rich solution treated groups as compared with those with AA. The number of BMNCs and CFUs increased markedly and the bone marrow microenvironment was also improved significantly. The experimental group restrained the cell apoptosis, relieved hyperemia and accelerated tissue repair. The number of CD4(+) and CD8(+) cells as well as the ratio of CD4/CD8 increased to normal gradually, while the levels of TNF-α, IFN-γ, and IL-6 in serum decreased after H2-rich solution treatment.
CONCLUSION: Our study firstly showed that hydrogen-rich solution accelerated the recovery of either hematological or immunological recovery on aplastic anemia mice. This finding suggests hydrogen-rich solution as a potential clinical therapeutic agent for AA.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/24008771
Anti-inflammation effects of hydrogen saline in LPS activated macrophages and carrageenan induced paw oedema
ABSTRACT
BACKGROUND: Oxidative stress is thought to play an important role in the pathogenesis of inflammation. Recent studies have found that hydrogen gas has the effect of eliminating free radicals. Whether hydrogen saline (more convenient to be used than hydrogen gas) has the anti-inflammation effect or not is still unknown.
METHODS: Carrageenan-induced paw oedema and LPS-activated macrophages are studied in this article. Injection of carrageenan into the foot of a mouse elicited an acute inflammatory response characterized by increase of foot volume and infiltration of neutrophils. While tumor necrosis factorα(TNF-α) secreted by activated macrophages was determined by ELISA and real-time PCR.
RESULTS: All parameters of inflammation (foot volume, infiltration of neutrophils, amount of TNF-α and the level of TNF-α’s mRNA) were attenuated by the hydrogen saline treatment.
CONCLUSION: As a more convenient way than inhaling H2, hydrogen saline exhibits a protective effect against inflammation and it might provide a novel therapeutic approach for inflammatory diseases.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/22296736
Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals
ABSTRACT
Acute oxidative stress induced by ischemia-reperfusion or inflammation causes serious damage to tissues, and persistent oxidative stress is accepted as one of the causes of many common diseases including cancer. We show here that hydrogen (H(2)) has potential as an antioxidant in preventive and therapeutic applications. We induced acute oxidative stress in cultured cells by three independent methods. H(2) selectively reduced the hydroxyl radical, the most cytotoxic of reactive oxygen species (ROS), and effectively protected cells; however, H(2) did not react with other ROS, which possess physiological roles. We used an acute rat model in which oxidative stress damage was induced in the brain by focal ischemia and reperfusion. The inhalation of H(2) gas markedly suppressed brain injury by buffering the effects of oxidative stress. Thus H(2) can be used as an effective antioxidant therapy; owing to its ability to rapidly diffuse across membranes, it can reach and react with cytotoxic ROS and thus protect against oxidative damage.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/17486089
Recent Progress Toward Hydrogen Medicine: Potential of Molecular Hydrogen for Preventive and Therapeutic Applications
ABSTRACT
Persistent oxidative stress is one of the major causes of most lifestyle-related diseases, cancer and the aging process. Acute oxidative stress directly causes serious damage to tissues. Despite the clinical importance of oxidative damage, antioxidants have been of limited therapeutic success. We have proposed that molecular hydrogen (H2) has potential as a “novel” antioxidant in preventive and therapeutic applications [Ohsawa et al., Nat Med. 2007: 13; 688-94]. H2 has a number of advantages as a potential antioxidant: H2 rapidly diffuses into tissues and cells, and it is mild enough neither to disturb metabolic redox reactions nor to affect reactive oxygen species (ROS) that function in cell signaling, thereby, there should be little adverse effects of consuming H2.
There are several methods to ingest or consume H2, including inhaling hydrogen gas, drinking H2-dissolved water (hydrogen water), taking a hydrogen bath, injecting H2-dissolved saline (hydrogen saline), dropping hydrogen saline onto the eye, and increasing the production of intestinal H2 by bacteria. Since the publication of the first H2 paper in Nature Medicine in 2007, the biological effects of H2 have been confirmed by the publication of more than 38 diseases, physiological states and clinical tests in leading biological/medical journals, and several groups have started clinical examinations.
Moreover, H2 shows not only effects against oxidative stress, but also various anti-inflammatory and anti-allergic effects. H2 regulates various gene expressions and protein-phosphorylations, though the molecular mechanisms underlying the marked effects of very small amounts of H2 remain elusive.
Reference-https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257754/
Hydrogen as a Selective Antioxidant: A Review of Clinical and Experimental Studies
ABSTRACT
Oxidative stress is implicated in the pathogenesis of many diseases; however, currently used antioxidants have a high toxicity that constrains administration to a narrow window of therapeutic dosage. There is a clear need for more effective and safer antioxidants. Diatomic hydrogen (H2) was proposed as a novel antioxidant that selectively reduces levels of toxic reactive-oxygen species. Recently, many studies have reported that H2 (inhaled or orally ingested, typically as approximately 0.8 mM H2-saturated water), can exert beneficial effects in diverse animal models of ischaemia–reperfusion injury, and inflammatory and neurological disease. In the clinic, oral administration of H2-saturated water is reported to improve lipid and glucose metabolism in subjects with diabetes or impaired glucose tolerance; promising results have also been obtained in reducing inflammation in haemodialysis patients and treating metabolic syndrome. These studies suggest H2 has selective antioxidant properties, and can exert antiapoptotic, anti-inflammatory and antiallergy effects. This review summarizes recent research findings and mechanisms concerning the therapeutic potential of H2.
Reference-https://journals.sagepub.com/doi/abs/10.1177/147323001003800602
The Role of Inflammation in the Pathology of Acne
Oxidative stress in acne vulgaris: an important therapeutic targetAddressing Free Radical Oxidationin Acne Vulgari
Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injuryHydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injuryHydrogen-rich water protects against acetaminophen-induced hepatotoxicity in miceHydrogen-rich water protects against acetaminophen-induced hepatotoxicity in miceHydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injuryHydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injuryHydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injuryInjuryHydrogen–water enhances5-fluorouracil-induced inhibition ofcolon cancerHydrogen–water enhances5-fluorouracil-induced inhibition ofcolon cancerHydrogen–water enhances5-fluorouracil-induced inhibition ofcolon cancerTop of Form
ABSTRACT
The conventional perspective of acne pathogenesis holds that Propionibacterium acnes colonizes the duct of the sebaceous follicle, causing an innate immune response and the progression from a so-called noninflammatory comedo to an inflammatory papule, pustule, or nodule.
However, this viewpoint has come under increasing scrutiny over the last decade, as evidence has emerged supporting a role for inflammation at all stages of acne lesion development, perhaps subclinically even before comedo formation. The immunochemical pathways underlying the initiation and propagation of the inflammation in acne are complex and still being elucidated, but may involve Propionibacterium acnes as well as several inflammatory mediators and their target receptors, including cytokines, defensins, peptidases, sebum lipids, and neuropeptides.
This review presents evidence to support the notion that acne is primarily an inflammatory disease, challenging the current nomenclature of noninflammatory versus inflammatory acne lesions and suggesting that the nomenclature is outdated and incorrect. The evidence in support of acne as an inflammatory disease also has clinical implications, in that anti-inflammatory drugs used to treat the disease can be expected to exert effects against all lesion stages, albeit via distinct mechanisms of anti-inflammation.
References-https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3780801/
Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome.
ABSTRACT
We have found that hydrogen (dihydrogen; H2) has beneficial lipid-lowering effects in high-fat diet-fed Syrian golden hamsters. The objective of this study was to characterize the effects of H2-rich water (0.9-1.0 l/day) on the content, composition, and biological activities of serum lipoproteins on 20 patients with potential metabolic syndrome. Serum analysis showed that consumption of H2-rich water for 10 weeks resulted in decreased serum total-cholesterol (TC) and LDL-cholesterol (LDL-C) levels. Western blot analysis revealed a marked decrease of apolipoprotein (apo)B100 and apoE in serum.
In addition, we found H2 significantly improved HDL functionality assessed in four independent ways, namely, i) protection against LDL oxidation, ii) inhibition of tumor necrosis factor (TNF)-α-induced monocyte adhesion to endothelial cells, iii) stimulation of cholesterol efflux from macrophage foam cells, and iv) protection of endothelial cells from TNF-α-induced apoptosis. Further, we found consumption of H2-rich water resulted in an increase in antioxidant enzyme superoxide dismutase and a decrease in thiobarbituric acid-reactive substances in whole serum and LDL. In conclusion, supplementation with H2-rich water seems to decrease serum LDL-C and apoB levels, improve dyslipidemia-injured HDL functions, and reduce oxidative stress, and it may have a beneficial role in prevention of potential metabolic syndrome.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/23610159
Recent Progress Toward Hydrogen Medicine: Potential of Molecular Hydrogen for Preventive and Therapeutic Applications
ABSTRACT
Persistent oxidative stress is one of the major causes of most lifestyle-related diseases, cancer and the aging process. Acute oxidative stress directly causes serious damage to tissues. Despite the clinical importance of oxidative damage, antioxidants have been of limited therapeutic success. We have proposed that molecular hydrogen (H2) has potential as a “novel” antioxidant in preventive and therapeutic applications [Ohsawa et al., Nat Med. 2007: 13; 688-94]. H2 has a number of advantages as a potential antioxidant: H2 rapidly diffuses into tissues and cells, and it is mild enough neither to disturb metabolic redox reactions nor to affect reactive oxygen species (ROS) that function in cell signaling, thereby, there should be little adverse effects of consuming H2. There are several methods to ingest or consume H2, including inhaling hydrogen gas, drinking H2-dissolved water (hydrogen water), taking a hydrogen bath, injecting H2-dissolved saline (hydrogen saline), dropping hydrogen saline onto the eye, and increasing the production of intestinal H2 by bacteria. Since the publication of the first H2 paper in Nature Medicine in 2007, the biological effects of H2 have been confirmed by the publication of more than 38 diseases, physiological states and clinical tests in leading biological/medical journals, and several groups have started clinical examinations. Moreover, H2 shows not only effects against oxidative stress, but also various anti-inflammatory and anti-allergic effects. H2 regulates various gene expressions and protein-phosphorylations, though the molecular mechanisms underlying the marked effects of very small amounts of H2 remain elusive.
Reference-https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257754/
Molecular Hydrogen as an Emerging Therapeutic Medical Gas for Neurodegenerative and Other Diseases
ABSTRACT
Oxidative stress is implicated in atherogenesis; however most clinical trials with dietary antioxidants failed to show marked success in preventing atherosclerotic diseases. We have found that hydrogen (dihydrogen; H2) acts as an effective antioxidant to reduce oxidative stress [I. Ohsawa, M. Ishikawa, K. Takahashi, M. Watanabe, K. Nishimaki, K. Yamagata, K. Katsura, Y. Katayama, S, Asoh, S. Ohta, Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals, Nat. Med. 13 (2007) 688–694]. Here, we investigated whether drinking H2-dissolved water at a saturated level (H2–water) ad libitum prevents arteriosclerosis using an apolipoprotein E knockout mouse (apoE−/−), a model of the spontaneous development of atherosclerosis. ApoE−/− mice drank H2–water ad libitum from 2 to 6 month old throughout the whole period. Atherosclerotic lesions were significantly reduced by ad libitum drinking of H2–water (p = 0.0069) as judged by Oil-Red-O staining series of sections of aorta. The oxidative stress level of aorta was decreased. Accumulation of macrophages in atherosclerotic lesions was confirmed. Thus, consumption of H2-dissolved water has the potential to prevent arteriosclerosis
Reference-https://www.hindawi.com/journals/omcl/2012/353152/
Consumption of hydrogen water prevents atherosclerosis in apolipoprotein E knockout mice
ABSTRACT
Oxidative stress is implicated in atherogenesis; however most clinical trials with dietary antioxidants failed to show marked success in preventing atherosclerotic diseases. We have found that hydrogen (dihydrogen; H2) acts as an effective antioxidant to reduce oxidative stress [I. Ohsawa, M. Ishikawa, K. Takahashi, M. Watanabe, K. Nishimaki, K. Yamagata, K. Katsura, Y. Katayama, S, Asoh, S. Ohta, Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals, Nat. Med. 13 (2007) 688–694]. Here, we investigated whether drinking H2-dissolved water at a saturated level (H2–water) ad libitum prevents arteriosclerosis using an apolipoprotein E knockout mouse (apoE−/−), a model of the spontaneous development of atherosclerosis. ApoE−/− mice drank H2–water ad libitum from 2 to 6 month old throughout the whole period. Atherosclerotic lesions were significantly reduced by ad libitum drinking of H2–water (p = 0.0069) as judged by Oil-Red-O staining series of sections of aorta. The oxidative stress level of aorta was decreased. Accumulation of macrophages in atherosclerotic lesions was confirmed. Thus, consumption of H2-dissolved water has the potential to prevent arteriosclerosis
Reference-https://www.sciencedirect.com/science/article/pii/S0006291X08021219
Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals
ABSTRACT
Acute oxidative stress induced by ischemia-reperfusion or inflammation causes serious damage to tissues, and persistent oxidative stress is accepted as one of the causes of many common diseases including cancer. We show here that hydrogen (H(2)) has potential as an antioxidant in preventive and therapeutic applications. We induced acute oxidative stress in cultured cells by three independent methods. H(2) selectively reduced the hydroxyl radical, the most cytotoxic of reactive oxygen species (ROS), and effectively protected cells; however, H(2) did not react with other ROS, which possess physiological roles. We used an acute rat model in which oxidative stress damage was induced in the brain by focal ischemia and reperfusion. The inhalation of H(2) gas markedly suppressed brain injury by buffering the effects of oxidative stress. Thus H(2) can be used as an effective antioxidant therapy; owing to its ability to rapidly diffuse across membranes, it can reach and react with cytotoxic ROS and thus protect against oxidative damage.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/17486089
Hydrogen‐supplemented drinking water protects cardiac allografts from inflammation‐associated deterioration
ABSTRACT
Recent evidence suggests that molecular hydrogen has therapeutic value for disease states that involve inflammation. We hypothesized that drinking hydrogen‐rich water (HW) daily would protect cardiac and aortic allograft recipients from inflammation‐associated deterioration. Heterotopic heart transplantation with short‐course tacrolimus immunosuppression and orthotopic aortic transplantation were performed in allogeneic rat strains. HW was generated either by bubbling hydrogen gas through tap water (Bu‐HW) or via chemical reaction using a magnesium 2H + stick [Mg2O → Mg (OH)2H + 2] immersed in tap water (Mg‐HW). Recipients were given either regular water (RW), Mg‐HW, Bu‐HW, or Mg‐HW that had been subsequently degassed (DW).
Graft survival was assessed by daily palpation for a heartbeat. Drinking Mg‐HW or Bu‐HW was remarkably effective in prolonging heart graft survival and reducing intimal hyperplasia in transplanted aortas as compared with grafts treated with RW or DW. Furthermore, T cell proliferation was significantly inhibited in the presence of hydrogen in vitro, accompanied by less production of interleukin‐2 and interferon‐γ. Hydrogen treatment was also associated with increased graft ATP levels and increased activity of the enzymes in mitochondrial respiratory chain. Drinking HW prolongs survival of cardiac allografts and reduces intimal hyperplasia of aortic allografts.
Reference-https://onlinelibrary.wiley.com/doi/full/10.1111/j.1432-2277.2012.01542.x
Hydrogen as a Selective Antioxidant: A Review of Clinical and Experimental Studies
ABSTRACT
Oxidative stress is implicated in the pathogenesis of many diseases; however, currently used antioxidants have a high toxicity that constrains administration to a narrow window of therapeutic dosage. There is a clear need for more effective and safer antioxidants. Diatomic hydrogen (H2) was proposed as a novel antioxidant that selectively reduces levels of toxic reactive-oxygen species. Recently, many studies have reported that H2 (inhaled or orally ingested, typically as approximately 0.8 mM H2-saturated water), can exert beneficial effects in diverse animal models of ischaemia–reperfusion injury, and inflammatory and neurological disease. In the clinic, oral administration of H2-saturated water is reported to improve lipid and glucose metabolism in subjects with diabetes or impaired glucose tolerance; promising results have also been obtained in reducing inflammation in haemodialysis patients and treating metabolic syndrome. These studies suggest H2 has selective antioxidant properties, and can exert antiapoptotic, anti-inflammatory and antiallergy effects. This review summarizes recent research findings and mechanisms concerning the therapeutic potential of H2.
Reference-https://journals.sagepub.com/doi/abs/10.1177/147323001003800602
Hydrogen-rich water prevents lipid deposition in the descending aorta in a rat periodontitis model
ABSTRACT
OBJECTIVE: Periodontitis has been causally linked to atherosclerosis, which is mediated by the oxidative stress. As hydrogen-rich water (HW) scavenges reactive oxygen species (ROS), we hypothesized that HW could prevent lipid deposition induced by periodontitis in the aorta. The aim of this study was to investigate the effects of HW on the initiation of atherosclerosis in a rat periodontitis model.
DESIGN: Eighteen 8-wk-old male Wistar rats were divided into three groups of six rats; the periodontitis group, periodontitis+HW group and the no treatment (control) group. In the periodontitis and periodontitis+HW groups, periodontitis was induced using a ligature for 4 wk, while the periodontitis+HW group was given water containing 800-1000 μg/L hydrogen during the 4-wk experimental period.
RESULTS: In the periodontitis group, lipid deposition in the descending aorta was observed. The periodontitis group also showed significant higher serum levels for ROS and oxidised low-density lipoprotein-cholesterol (ox-LDL) (1.7 and 1.4 times, respectively), and higher aortic expression levels of nitrotyrosine and hexanoyl-lysine (HEL) (7.9 and 16.0 times, respectively), as compared to the control group (p<0.05). In the periodontitis+HW group, lipid deposition was lower. Lower serum levels of ROS and ox-LDL (0.46 and 0.82 times, respectively) and lower aortic levels of nitrotyrosine and HEL (0.27 and 0.19 times, respectively) were observed in the periodontitis+HW group than in the periodontitis group (p<0.05).
CONCLUSIONS: HW intake may prevent lipid deposition in the rat aorta induced by periodontitis by decreasing serum ox-LDL levels and aortic oxidative stress.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/22607937
The evolution of molecular hydrogen: a noteworthy potential therapy with clinical significance
ABSTRACT
Studies on molecular hydrogen have evolved tremendously from its humble beginnings and have continued to change throughout the years. Hydrogen is extremely unique since it has the capability to act at the cellular level. Hydrogen is qualified to cross the blood brain barrier, to enter the mitochondria, and even has the ability to translocate to the nucleus under certain conditions.
Once in these ideal locations of the cell, previous studies have shown that hydrogen exerts antioxidant, anti-apoptotic, anti-inflammatory, and cytoprotective properties that are beneficial to the cell. Hydrogen is most commonly applied as a gas, water, saline, and can be applied in a variety of other mediums.
There are also few side effects involving hydrogen, thus making hydrogen a perfect medical gas candidate for the convention of novel therapeutic strategies against cardiovascular, cerebrovascular, cancer, metabolic, and respiratory diseases and disorders. Although hydrogen appears to be faultless at times, there still are several deficiencies or snares that need to be investigated by future studies. This review article seeks to delve and comprehensively analyze the research and experiments that alludes to molecular hydrogen being a novel therapeutic treatment that medicine desperately needs.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/23680032
Hydrogen water consumption prevents osteopenia in ovariectomized rats.
ABSTRACT
BACKGROUND AND PURPOSE:
Accumulating evidence indicates an important role of oxidative stress in the progression of osteoporosis. Recently, it was demonstrated that hydrogen gas, as a novel antioxidant, could selectively reduce hydroxyl radicals and peroxynitrite anion to exert potent therapeutic antioxidant activity. The aim of the present work was to investigate the effect of hydrogen water (HW) consumption on ovariectomy-induced osteoporosis.
EXPERIMENTAL APPROACH:
Ovariectomized rats were fed with HW (1.3 ± 0.2 mg·L⁻¹) for 3 months. Then, blood was collected and femur and vertebrae were removed for evaluation of the effect of HW on bone.
KEY RESULTS:
HW consumption in ovariectomized rats had no significant effect on oestrogen production, but prevented the reduction of bone mass including
bone mineral content and bone mineral density in femur and vertebrae, and preserved mechanical strength including ultimate load, stiffness, and energy, and bone structure including trabecular bone volume fraction, trabecular number, and trabecular thickness in femur, and preserved mechanical strength including ultimate load and stiffness, and bone structure including trabecular bone volume fraction and trabecular number in vertebrae. In addition, treatment with HW abated oxidative stress and suppressed IL-6 and TNF-α mRNA expressions in femur of ovariectomized rats; treatment with HW increased femur endothelial NOS activity and enhanced circulating NO level in ovariectomized rats.
CONCLUSIONS AND IMPLICATIONS:
HW consumption prevents osteopenia in ovariectomized rats possibly through the ablation of oxidative stress induced by oestrogen withdrawal.
Reference – https://www.ncbi.nlm.nih.gov/pubmed/23121335
Effect of molecular hydrogen saturated alkaline electrolyzed water on disuse muscle atrophy in gastrocnemius muscle.
ABSTRACT
The objectives of this paper were to determine the level of oxidative stress in atrophied gastrocnemius, and to verify the effect of molecular hydrogen (H2) saturated alkaline electrolyzed water (HSW) on gastrocnemius atrophy by modifying the redox status, indicated by 8-hydroxy-2′-deoxyguanosine (8-OHdG), malondialdehyde (MDA), and superoxide dismutase (SOD)-like activity. Female Wistar rats were divided into four groups: (1) the control (CONT); (2) the Hindlimb unloading (HU, for 3 weeks) given purified normal water (HU-NW); (3) the HU given alkaline electrolyzed reduced water (HU-AEW); and (4) the HU given HSW (HU-HSW). We showed that 8-OHdG, but not MDA, significantly increased by 149% and 145% in HU-NW and HU-AEW, respectively, when compared with CONT. In contrast, there was a trend toward suppression in 8-OHdG levels (increased by 95% compared with CONT) by treatment of HSW, though this effect was not prominent. Additionally, SOD-like activity significantly increased in both HU-NW (184%) and HU-AEW (199%) when compared with CONT. This result suggests the elevation of O2-· in the atrophied gastrocnemius. However, upregulation of
SOD-like activity in the HU-HSW was increased by only 169% compared with CONT, though this difference is too small to detect statistical significance.
HU led to 13% and 15% reduction of gastrocnemius wet weights in HU-NW and HU-AEW, respectively, compared with CONT. And the reduction of gastrocnemius wet weights in HU-HSW was attenuated by 7% compared with CONT. The gastrocnemius wet weights in the HU-HSW group were significantly greater than those in the HU-AEW, but not statistically significant with HU-NW. These results indicate that HU causes an increase in oxidative stress, but, in this experimental protocol, continuous consumption of HSW during HU does not demonstrate successful attenuation of oxidative stress and HU-mediated gastrocnemius atrophy.
Reference – https://www.ncbi.nlm.nih.gov/pubmed/21963827
Treatment with hydrogen molecule alleviates TNFα-induced cell injury in osteoblast.
ABSTRACT
Tumor necrosis factor-alpha (TNFα) plays a crucial role in inflammatory diseases such as rheumatoid arthritis and postmenopausal osteoporosis. Recently, it has been demonstrated that hydrogen gas, known as a novel antioxidant, can exert therapeutic anti-inflammatory effect in many diseases. In this study, we investigated the effect of treatment with hydrogen molecule (H(2)) on TNFα-induced cell injury in osteoblast. The osteoblasts isolated from neonatal rat calvariae were cultured. It was found that TNFα suppressed cell viability, induced cell apoptosis, suppressed Runx2 mRNA expression, and inhibited alkaline phosphatase activity, which was reversed by co-incubation with H(2). Incubation with TNFα-enhanced intracellular reactive oxygen species (ROS) formation and malondialdehyde production increased NADPH oxidase activity, impaired mitochondrial function marked by increased mitochondrial ROS formation and decreased mitochondrial membrane potential and ATP synthesis, and suppressed activities of antioxidant enzymes including SOD and catalase, which were restored by co-incubation with H(2). Treatment with H(2) inhibited TNFα-induced activation of NFκB pathway. In addition, treatment with H(2) inhibited TNFα-induced nitric oxide (NO) formation through inhibiting iNOS
activity. Treatment with H(2) inhibited TNFα-induced IL-6 and ICAM-1 mRNA expression. In conclusion, treatment with H(2) alleviates TNFα-induced cell injury in osteoblast through abating oxidative stress, preserving mitochondrial function, suppressing inflammation, and enhancing NO bioavailability.
Reference – https://www.ncbi.nlm.nih.gov/pubmed/23212446
Hydrogen-rich saline alleviates early brain injury via reducing oxidative stress and brain edema following experimental subarachnoid hemorrhage in rabbits.
ABSTRACT
BACKGROUND:
Increasing experimental and clinical data indicate that early brain injury (EBI) after subarachnoid hemorrhage (SAH) largely contributes to unfavorable outcomes, and it has been proved that EBI following SAH is closely associated with oxidative stress and brain edema. The present study aimed to examine the effect of hydrogen, a mild and selective cytotoxic oxygen radical scavenger, on oxidative stress injury, brain edema and neurology outcome following experimental SAH in rabbits.
RESULTS:
The level of MDA, caspase-12/3 and brain water content increased significantly at 72 hours after experimental SAH. Correspondingly, obvious brain injury was found in the SAH group by terminal deoxynucleotidyl transferase-mediated uridine 5′-triphosphate-biotin nick end-labeling (TUNEL) and Nissl staining. Similar results were found in the SAH+saline group. In contrast, the upregulated level of MDA, caspase-12/3 and brain edema was attenuated and the brain injury was substantially alleviated in the hydrogen treated rabbits, but the improvement of neurology outcome was not obvious.
CONCLUSION:
The results suggest that treatment with hydrogen in experimental SAH rabbits could alleviate brain injury via decreasing the oxidative stress injury and brain edema. Hence, we conclude that hydrogen possesses the potential to be a novel therapeutic agent for EBI after SAH.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/22587664
Nuclear factor-κB/Bcl-XL pathway is involved in the protective effect of hydrogen-rich saline on the brain following experimental subarachnoid hemorrhage in rabbits.
ABSTRACT
Early brain injury (EBI), a significant contributor to poor outcome after subarachnoid hemorrhage (SAH), is intimately associated with neuronal apoptosis. Recently, the protective role of hydrogen (H2 ) in the brain has been widely studied, but the underlying mechanism remains elusive. Numerous studies have shown nuclear factor-κB (NF-κB) as a crucial survival pathway in neurons. Here we investigated the role of H2 in EBI following SAH, focusing on the NF-κB pathway. A double blood injection model was used to produce experimental SAH, and H2 -rich saline was injected intraperitoneally. NF-κB activity within the occipital cortex was measured. Immunofluorescence was performed to demonstrate the activation of NF-κB; Bcl-xL and cleaved caspase-3 were determined via Western blot. Gene expression of Bcl-xL was detected by real-time PCR, and TUNEL and Nissl staining were performed to illustrate brain injury in the occipital cortex. SAH induced a significant increase of cleaved caspase-3. Correspondingly, TUNEL staining demonstrated obvious neuronal apoptosis following SAH. In contrast, H2 treatment markedly increased NF-κB activity and the expression of Bcl-xL and decreased the level of cleaved caspase-3. Additionally, H2 treatment significantly reduced post-SAH neuronal apoptosis.
The current study shows that H2 treatment alleviates EBI in the rabbits following SAH and that NF-κB/Bcl-xL pathway is involved in the protective role of H2 .
Reference-https://www.ncbi.nlm.nih.gov/pubmed/24105634
Hydrogen-rich saline reverses oxidative stress, cognitive impairment, and mortality in rats submitted to sepsis by cecal ligation and puncture.
ABSTRACT
BACKGROUND:
Sepsis is associated with high morbidity and mortality, and survivors can present with cognitive dysfunction. The present study was performed to investigate the effects of hydrogen-rich saline (HRS) on oxidative stress in the brain, cognitive dysfunction, and mortality in a rat model of sepsis.
METHODS:
A rat model of sepsis was induced by cecal ligation and puncture. Physiologic saline or HRS was administered intraperitoneally (2.5 mL/kg or 10 mL/kg) 10 min before the operation. The survival rate was recorded, and cognitive function was tested using the Morris water maze. The reactive oxygen species and malondialdehyde levels and superoxide dismutase activity in the hippocampus were observed to evaluate the oxidative stress levels. The caspase 3 levels were measured to detect apoptosis. The histopathologic changes in the hippocampus were evaluated by hematoxylin-eosin staining and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay.
RESULTS:
Cecal ligation and puncture resulted in a poor survival rate, evidence of brain injury, and cognitive dysfunction. The hippocampal reactive oxygen species and malondialdehyde levels increased significantly, and superoxide dismutase activity decreased significantly. HRS reversed these changes in a dose-dependent manner.
CONCLUSIONS:
These findings indicate that HRS could attenuate the consequences of sepsis induced by cecal ligation and puncture in rats, at least in part, by the inhibition of oxidative stress.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/22482765
Hydrogen-rich saline controls remifentanil-induced hypernociception and NMDA receptor NR1 subunit membrane trafficking through GSK-3β in the DRG in rats.
ABSTRACT
BACKGROUND:
Although NMDAR trafficking mediated by GSK-3β involvement in transmission of pronociceptive messages in the spinal cord has been confirmed by our previous studies, whether NMDAR trafficking is implicated in peripheral sensitization remains equivocal. It is demonstrated that inflammation is associated with spinal NMDAR-containing nociceptive neurons activation and the maintenance of opioid induced pain hypersensitivity. However, whether and how hydrogen-rich saline, as an effective anti-inflammatory drug, could prevent hyperalgesia through affecting peripheral sensitization caused by NMDAR activation remains to be explored.
METHODS:
To test these effects, hydrogen-rich saline (2.5, 5 or 10 ml/kg) was administrated intraperitoneally after remifentanil infusion, NMDAR antagonist MK-801 or GSK-3β inhibitor TDZD-8 was administrated intravenously before remifentanil infusion in rats. We examined time course of hydrogen concentration in blood after hydrogen-rich saline administration. Mechanical and thermal hyperalgesia were evaluated by measuring PWT and PWL for 48 post-infusion hours, respectively. Western blotting and real-time qPCR assay were applied to analyze the NR1 membrane trafficking, GSK-3β expression and activity in DRG. Inflammatory mediators (TNF-α, IL-1β, and IL-6) expressions in DRG were also analyzed.
RESULTS:
We found that NR1 membrane trafficking in DRG increased, possibly due to GSK-3β activation after remifentanil infusion. We also discovered that hydrogen-rich saline not 2.5 ml/kg but 5 and 10 ml/kg could dose-dependently attenuate mechanical and thermal hyperalgesia without affecting baseline nociceptive threshold, reduce expressions of inflammatory mediators (TNF-α, IL-1β, and IL-6) and decrease NR1 trafficking mediated by GSK-3β, and minimal effective concentration was observed to be higher than 10 μmol/L, namely peak concentration in arterial blood after administration of HRS 2.5 ml/kg without any influence on hyperalgesia.
CONCLUSION:
Our results indicated that antihyperalgesic effect of hydrogen-rich saline might depend predominantly on its ability to reverse NR1 trafficking via inhibition of GSK-3β activity in DRG in a dose-dependent manner.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/24951883
Hydrogen gas ameliorates oxidative stress in early brain injury after subarachnoid hemorrhage in rats.
ABSTRACT
OBJECTIVE:
Hydrogen gas has been demonstrated to neutralize free radicals and reduce oxidative stress recently. Our objective was to determine the therapeutic effect of H2 inhalation and its antioxidative activity on early brain injury after subarachnoid hemorrhage.
DESIGN:
Controlled in vivo laboratory study.
SETTING:
Animal research laboratory.
SUBJECTS:
One hundred thirty-seven adult male Sprague-Dawley rats weighing 280-350 g.
INTERVENTIONS:
Subarachnoid hemorrhage was induced by endovascular perforation method in rats. Subarachnoid hemorrhage rats were treated with 2.9% hydrogen gas inhaled for 2 hrs after perforation. At 24 and 72 hrs, mortality, body weight, neurologic deficits, and brain water content were assessed. Blood-brain barrier permeability and apoptosis were also measured at 24 hrs. To investigate the antioxidative activity of hydrogen gas, the expression of malondialdehyde, nitrotyrosine, and 8-hydroxyguanosine, which are oxidative markers of lipid, protein, and DNA damage, respectively, were measured at 24 hrs.
MEASUREMENTS AND MAIN RESULTS:
Hydrogen gas significantly alleviated brain edema and blood-brain barrier disruption, reduced apoptosis, and improved neurologic function at 24 hrs but not 72 hrs after subarachnoid hemorrhage. These effects were associated with the amelioration of oxidative injury of lipid, protein, and DNA.
CONCLUSIONS:
Hydrogen gas could exert its neuroprotective effect against early brain injury after subarachnoid hemorrhage by its antioxidative activity.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/22336722
Hydrogen supplementation of preservation solution improves viability of osteochondral grafts.
ABSTRACT
Allogenic osteochondral tissue (OCT) is used for the treatment of large cartilage defects. Typically, OCTs collected during the disease-screening period are preserved at 4°C; however, the gradual reduction in cell viability during cold preservation adversely affects transplantation outcomes. Therefore, improved storage methods that maintain the cell viability of OCTs are needed to increase the availability of high-quality OCTs and improve treatment outcomes. Here, we evaluated whether long-term hydrogen delivery to preservation solution improved the viability of rat OCTs during cold preservation. Hydrogen-supplemented Dulbecco’s Modified Eagles Medium (DMEM) and University of Wisconsin (UW) solution both significantly improved the cell viability of OCTs during preservation at 4°C for 21 days compared to nonsupplemented media. However, the long-term cold preservation of OCTs in DMEM containing hydrogen was associated with the most optimal maintenance of chondrocytes with respect to viability and morphology. Our findings demonstrate that OCTs preserved in DMEM supplemented with hydrogen are a promising material for the repair of large cartilage defects in the clinical setting.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/25506061
Hydrogen rich saline reduces immune-mediated brain injury in rats with acute carbon monoxide poisoning.
ABSTRACT
OBJECTIVES:
This experiment was designed to determine whether hydrogen (H(2)) rich saline can ameliorate brain abnormalities in a rat model with acute carbon monoxide (CO) poisoning.
METHODS:
Sprague-Dawley male rats were used for CO poisoning and H(2) rich saline treatment. Changes in neurons, microglias, and myelin sheath were observed by electron microscope. Neuron loss was assessed by Nissl staining. Antioxidant capacities were evaluated by studying superoxide dismutase activities and malondialdehyde concentration in the brain and serum. Infiltration of macrophages, expression of immune-associated cytokines (MIP-1-alpha and ICAM-1), and changes in myelin basic protein (MBP) were monitored by immunohistochemical staining and western blotting.
RESULTS:
CO-exposed rats showed the increase in neuron loss and the decrease in antioxidant capacities. And H(2) rich saline given after CO poisoning can prevent the alterations mentioned above. CO-mediated oxidative stress caused alterations in MBP, which
initiated an adaptive immunological response that led to brain injury. MBP from H(2) rich saline-treated, CO-exposed rats was recognized normally by immunohistochemical staining and western blotting. Electron microscope observation from CO-exposed rats showed an apparent aggregation of microglias. Macrophages from CO-exposed rats were significantly more than those from H(2) rich saline-treated and control rats, and the immunofluorescence observation showed that macrophages were similar to microglias in type. Expression levels of MIP-1-alpha and ICAM-1 increased in the brains of CO-poisoned rats and H(2) rich saline treatment decreased the levels.
DISCUSSION:
The results indicate that H(2) rich saline prevents immune-mediated brain injury after CO poisoning.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/23146304
Hydrogen is neuroprotective against surgically induced brain injury
ABSTRACT
BACKGROUND: Neurosurgical operations cause unavoidable damage to healthy brain tissues. Direct surgical injury as well as surgically induced oxidative stress contributes to the subsequent formation of brain edema. Therefore, we tested the neuroprotective effects of hydrogen (H2) in an established surgical brain injury (SBI) model in rats.
MATERIALS AND METHODS: Adult male Sprague – Dawley rats (weight 300-350g) were divided into three groups to serve as sham operated, SBI without treatment, and SBI treated with H2 (2.9%). Brain water content, myeloperoxidase (MPO) assay, lipid peroxidation (LPO), and neurological function were measured at 24 hrs after SBI.
RESULTS: SBI resulted in localized brain edema (p = < 0.001). Hydrogen (2.9%) administered concurrently with surgery significantly decreased the formation of cerebral edema (p = 0.028) and improved neurobehavioral score (p = 0.022). However, hydrogen treatment failed to reduce oxidative stress (LPO assay) or inflammation (MPO assay) in brain tissues.
CONCLUSIONS: Hydrogen appears to be promising as an effective, yet inexpensive way to reduce cerebral edema caused by surgical procedures. Hydrogen has the potential to improve clinical outcome, decrease hospital stay, and reduce overall cost to patients and the health care system.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/22146427
Hydrogen-rich water protects against ischemic brain injury in rats by regulating calcium buffering proteins
ABSTRACT
Hydrogen-rich water (HRW) has anti-oxidant activities, and it exerts neuroprotective effects during ischemia-reperfusion brain injury. Parvalbumin and hippocalcin are two calcium buffering proteins, which are involved in neuronal differentiation, maturation and apoptosis. The aim of this study was to investigate whether HRW could moderate parvalbumin and hippocalcin expression during ischemic brain injury and glutamate toxicity-induced neuronal cell death.
Focal brain ischemia was induced in male Sprague-Dawley rats by middle cerebral artery occlusion (MCAO). Rats were treated with H2O or HRW (6 ml/kg per rat) before and after MCAO, and cerebral cortical tissues were collected 1, 7 and 14 days after MCAO. Based on our results, HRW treatment was able to reduce brain infarct volume and improve neurological function following ischemic brain injury.
In addition, HRW prevented the ischemia-induced reduction of parvalbumin and hippocalcin levels in vivo and also reduced the glutamate toxicity-induced death of neurons, including the dose-dependent reduction of glutamate toxicity-associated proteins in vitro. Moreover, HRW attenuated the glutamate toxicity-induced elevate in intracellular Ca(2+) levels. All these results suggest that HRW could protect against ischemic brain injury and that the maintenance of parvalbumin and hippocalcin levels by HRW during ischemic brain injury might contribute to the neuroprotective effects against neuron damage.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/25920370
Hydrogen inhalation ameliorated mast cell-mediated brain injury after intracerebral hemorrhage in mice
ABSTRACT
OBJECTIVE: Hydrogen inhalation was neuroprotective in several brain injury models. Its mechanisms are believed to be related to antioxidative stress. We investigated the potential neurovascular protective effect of hydrogen inhalation especially effect on mast cell activation in a mouse model of intracerebral hemorrhage.
DESIGN: Controlled in vivo laboratory study.
SETTING: Animal research laboratory.
SUBJECTS: One hundred seventy-one 8-week-old male CD-1 mice were used.
INTERVENTIONS: Collagenase-induced intracerebral hemorrhage model in 8-week-old male CD-1 mice was used. Hydrogen was administrated via spontaneous inhalation. The blood-brain barrier permeability and neurologic deficits were investigated at 24 and 72 hours after intracerebral hemorrhage. Mast cell activation was evaluated by Western blot and immuno-staining. The effects of hydrogen inhalation on mast cell activation were confirmed in an autologous blood injection model intracerebral hemorrhage.
MEASUREMENT AND MAIN RESULTS: At 24 and 72 hours post intracerebral hemorrhage, animals showed blood-brain barrier disruption, brain edema, and neurologic deficits, accompanied with phosphorylation of Lyn kinase and release of tryptase, indicating mast cell activation. Hydrogen treatment diminished phosphorylation of Lyn kinase and release of tryptase, decreased accumulation and degranulation of mast cells, attenuated blood-brain barrier disruption, and improved neurobehavioral function.
CONCLUSION: Activation of mast cells following intracerebral hemorrhage contributed to increase of blood-brain barrier permeability and brain edema. Hydrogen inhalation preserved blood-brain barrier disruption by prevention of mast cell activation after intracerebral hemorrhage.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/23388512
The evolution of molecular hydrogen: a noteworthy potential therapy with clinical significance
ABSTRACT
Studies on molecular hydrogen have evolved tremendously from its humble beginnings and have continued to change throughout the years. Hydrogen is extremely unique since it has the capability to act at the cellular level. Hydrogen is qualified to cross the blood brain barrier, to enter the mitochondria, and even has the ability to translocate to the nucleus under certain conditions. Once in these ideal locations of the cell, previous studies have shown that hydrogen exerts antioxidant, anti-apoptotic, anti-inflammatory, and cytoprotective properties that are beneficial to the cell. Hydrogen is most commonly applied as a gas, water, saline, and can be applied in a variety of other mediums. There are also few side effects involving hydrogen, thus making hydrogen a perfect medical gas candidate for the convention of novel therapeutic strategies against cardiovascular, cerebrovascular, cancer, metabolic, and respiratory diseases and disorders. Although hydrogen appears to be faultless at times, there still are several deficiencies or snares that need to be investigated by future studies. This review article seeks to delve and comprehensively analyze the research and experiments that alludes to molecular hydrogen being a novel therapeutic treatment that medicine desperately needs.
Reference-https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660246/
Hydrogen-rich saline alleviates early brain injury via reducing oxidative stress and brain edema following experimental subarachnoid hemorrhage in rabbits
ABSTRACT
BACKGROUND: Increasing experimental and clinical data indicate that early brain injury (EBI) after subarachnoid hemorrhage (SAH) largely contributes to unfavorable outcomes, and it has been proved that EBI following SAH is closely associated with oxidative stress and brain edema. The present study aimed to examine the effect of hydrogen, a mild and selective cytotoxic oxygen radical scavenger, on oxidative stress injury, brain edema and neurology outcome following experimental SAH in rabbits.
RESULTS: The level of MDA, caspase-12/3 and brain water content increased significantly at 72 hours after experimental SAH. Correspondingly, obvious brain injury was found in the SAH group by terminal deoxynucleotidyl transferase-mediated uridine 5′-triphosphate-biotin nick end-labeling (TUNEL) and Nissl staining. Similar results were found in the SAH+saline group. In contrast, the upregulated level of MDA, caspase-12/3 and brain edema was attenuated and the brain injury was substantially alleviated in the hydrogen treated rabbits, but the improvement of neurology outcome was not obvious.
CONCLUSION: The results suggest that treatment with hydrogen in experimental SAH rabbits could alleviate brain injury via decreasing the oxidative stress injury and brain edema. Hence, we conclude that hydrogen possesses the potential to be a novel therapeutic agent for EBI after SAH.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/22587664
Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals
ABSTRACT
Acute oxidative stress induced by ischemia-reperfusion or inflammation causes serious damage to tissues, and persistent oxidative stress is accepted as one of the causes of many common diseases including cancer. We show here that hydrogen (H(2)) has potential as an antioxidant in preventive and therapeutic applications. We induced acute oxidative stress in cultured cells by three independent methods. H(2) selectively reduced the hydroxyl radical, the most cytotoxic of reactive oxygen species (ROS), and effectively protected cells; however, H(2) did not react with other ROS, which possess physiological roles. We used an acute rat model in which oxidative stress damage was induced in the brain by focal ischemia and reperfusion. The inhalation of H(2) gas markedly suppressed brain injury by buffering the effects of oxidative stress. Thus H(2) can be used as an effective antioxidant therapy; owing to its ability to rapidly diffuse across membranes, it can reach and react with cytotoxic ROS and thus protect against oxidative damage.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/17486089
Hydrogen is neuroprotective against surgically induced brain injury
ABSTRACT
BACKGROUND: Neurosurgical operations cause unavoidable damage to healthy brain tissues. Direct surgical injury as well as surgically induced oxidative stress contributes to the subsequent formation of brain edema. Therefore, we tested the neuroprotective effects of hydrogen (H2) in an established surgical brain injury (SBI) model in rats.
MATERIALS AND METHODS: Adult male Sprague – Dawley rats (weight 300-350g) were divided into three groups to serve as sham operated, SBI without treatment, and SBI treated with H2 (2.9%). Brain water content, myeloperoxidase (MPO) assay, lipid peroxidation (LPO), and neurological function were measured at 24 hrs after SBI.
RESULTS: SBI resulted in localized brain edema (p = < 0.001). Hydrogen (2.9%) administered concurrently with surgery significantly decreased the formation of cerebral edema (p = 0.028) and improved neurobehavioral score (p = 0.022). However, hydrogen treatment failed to reduce oxidative stress (LPO assay) or inflammation (MPO assay) in brain tissues.
CONCLUSIONS: Hydrogen appears to be promising as an effective, yet inexpensive way to reduce cerebral edema caused by surgical procedures. Hydrogen has the potential to improve clinical outcome, decrease hospital stay, and reduce overall cost to patients and the health care system.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/22146427
Hydrogen-rich saline attenuates chemotherapy-induced ovarian injury via regulation of oxidative stress
ABSTRACT
Hydrogen has been reported to exert a therapeutic effect in several diseases due to its antioxidative, anti-inflammatory and anti-apoptotic properties. The aim of the present study was to investigate whether hydrogen-rich saline treatment could attenuate ovarian damage induced by cisplatin. A total of 240 adult, virgin, female Sprague Dawley rats, weighing 180-220 g, were randomly divided into four groups (n=60 per group): Control (Con), control + hydrogen-rich saline (Con + H2), cisplatin-induced ovarian injury (OI) and cisplatin-induced ovarian injury + hydrogen-rich saline (OI + H2). Cisplatin was diluted in saline immediately before use. In the OI and OI + H2 groups, the rats were administered a dose of cisplatin on the 1st and 7th days. The rats in the Con + H2 and OI + H2 groups were intraperitoneally injected with hydrogen-rich saline (10ml/kg body weight) once a day over a 2-week period. On the 14th, 28th and 42nd days (T1, T2 and T3) after the cisplatin injection, femoral vein blood was collected. At the end of the experiment, ovarian homogenates were prepared, and the samples were used for estrogen (E2), follicle-stimulating hormone (FSH), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) examination. In addition, rats (n=10 per group) were sacrificed for bilateral ovary removal; one was fixed in formalin for follicle-counting analysis, while the other was used for nuclear factor erythroid 2-related factor 2 (Nrf2) detection by western blotting. Hydrogen-rich saline attenuated the FSH release, elevated the level of E2, improved the development of follicles, and reduced the damage to the ovarian cortex at T1, T2 and T3 in the OI + H2 rats. Cisplatin induced oxidative stress by increasing the levels of oxidation products and attenuating the activity of antioxidant enzyme, which could be reversed by hydrogen-rich saline treatment. Furthermore, hydrogen-rich saline regulated the Nrf2 protein expression in rats with ovarian damage. In conclusion, hydrogen-rich saline exerts a protective effect against cisplatin-induced ovarian injury by reducing MDA and increasing SOD and CAT activity. Ovarian injury induced by chemotherapy involves the activation of Nrf2.
Reference-https://www.spandidos-publications.com/etm/10/6/2277
Hydrogen-rich water prevents progression of nonalcoholic steatohepatitis and accompanying hepatocarcinogenesis in mice
ABSTRACT
Oxidative stress is a strong contributor to the progression from simple fatty liver to nonalcoholic steatohepatitis (NASH). Molecular hydrogen is an effective antioxidant that reduces cytotoxic reactive oxygen species. In this study, we investigated the effects of hydrogen-rich water and the drug pioglitazone on the progression of NASH in mouse models. A methionine-choline-deficient (MCD) diet mouse model was prepared. Mice were divided into three experimental groups and fed for 8 weeks as follows: (1) MCD diet + control water (CW group); (2) MCD diet + hydrogen-rich water (HW group); and (3) MCD diet mixed with pioglitazone (PGZ group). Plasma alanine aminotransferase levels, hepatic expression of tumor necrosis factor-α, interleukin-6, fatty acid synthesis-related genes, oxidative stress biomarker 8-hydroxydeoxyguanosine (8-OHdG), and apoptosis marker terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive cells in the liver were decreased in the HW and PGZ groups. The HW group showed a smaller decrease in hepatic cholesterol; however, stronger antioxidative effects in serum and lower peroxisome proliferator-activated receptor-α expression in the liver were seen in comparison with the PGZ group. We then investigated the effects of hydrogen in the prevention of hepatocarcinogenesis in STAM mice, known as the NASH-related hepatocarcinogenesis model. Eight-week-old male STAM mice were divided into three experimental groups as follows: (1) control water (CW-STAM); (2) hydrogen-rich water (HW-STAM); and (3) pioglitazone (PGZ-STAM). After 8 weeks, hepatic tumors were evaluated. The number of tumors was significantly lower in the HW-STAM and PGZ-STAM groups than in the CW-STAM group. The maximum tumor size was smaller in the HW-STAM group than in the other groups.
Conclusion:
Consumption of hydrogen-rich water may be an effective treatment for NASH by reducing hepatic oxidative stress, apoptosis, inflammation, and hepatocarcinogenesis.
Reference-https://www.researchgate.net/publication/224039100_Hydrogen-rich_water_prevents_progression_of_nonalcoholic_steatohepatitis_and_accompanying_hepatocarcinogenesis_in_mice
Hydrogen-rich water improves neurological functional recovery in experimental autoimmune encephalomyelitis mice
ABSTRACT
Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS). The high costs, inconvenient administration, and side effects of current Food and Drug Administration (FDA)-approved drugs often lead to poor adherence to the long-term treatment of MS. Molecular hydrogen (H2) has been reported to exhibit anti-oxidant, anti-apoptotic, anti-inflammatory, anti-allergy, and anti-cancer effects. In the present study, we explored the prophylactic and therapeutic effects of hydrogen-rich water (HRW) on the progress of experimental autoimmune encephalomyelitis (EAE), the animal model for MS. We found that prophylactic administration of both 0.36mM and 0.89mM HRW was able to delay EAE onset and reduce maximum clinical scores. Moreover, 0.89mM HRW also reduced disease severity, CNS infiltration, and demyelination when administered after the onset of disease. Furthermore, HRW treatment prevented infiltration of CD4(+) T lymphocytes into the CNS and inhibited Th17 cell development without affecting Th1 cell populations. Because HRW is non-toxic, inexpensive, easily administered, and can readily cross the blood-brain barrier, our experiments suggest that HRW may have great potential in the treatment of MS.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/27138092
Hyperbaric hydrogen therapy: a possible treatment for cancer
ABSTRACT
Hairless albino mice with squamous cell carcinoma were exposed to a mixture of 2.5 percent oxygen and 97.5 percent hydrogen at a total pressure of 8 atmospheres for periods up to 2 weeks in order to see if a free radical decay catalyzer, such as hydrogen, would cause a regression of the skin tumors. Marked aggression of the tumors was found, leading to the possibility that hyperbaric hydrogen therapy might also prove to be of significance in the treatment of other types of cancer.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/1166304
Hydrogen protects mice from radiation induced thymic lymphoma in BALB/c mice
ABSTRACT
Ionizing radiation (IR) is a well-known carcinogen, however the mechanism of radiation induced thymic lymphoma is not well known. Moreover, an easy and effective method to protect mice from radiation induced thymic lymphoma is still unknown. Hydrogen, or H(2), is seldom regarded as an important agent in medical usage, especially as a therapeutic gas. Here in this study, we found that H(2) protects mice from radiation induced thymic lymphoma in BALB/c mice.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/21448340/
Consumption of hydrogen-rich water protects against ferric nitrilotriacetate-induced nephrotoxicity and early tumor promotional events in rats
ABSTRACT
The aim of this work was to test whether consumption with hydrogen-rich water (HW) alleviated renal injury and inhibited early tumor promotional events in Ferric nitrilotriacetate (Fe-NTA)-treated rats. Rats were injected with Fe-NTA solution (7.5mg Fe/kg body weight) intraperitoneally to induce renal injury and simultaneously treated with HW (1.3 ± 0.2mg/l).
We found that consumption with HW ameliorated Fe-NTA-induced renal injuries including suppressing elevation of serum creatinine and blood urea nitrogen and inhibited early tumor promotional events including decreasing ornithine decarboxylase activity and incorporation of [3H]thymidine into renal DNA.
Consumption with HW suppressed Fe-NTA-induced oxidative stress through decreasing formation of lipid peroxidation and peroxynitrite and activities of NADPH oxidase and xanthine oxidase, increasing activity of catalase, and restoring mitochondrial function in kidneys. Consumption with HW suppressed Fe-NTA-induced inflammation marked by reduced NF-κB, IL-6, and MCP-1 expression and macrophage accumulating in kidneys. In addition, consumption with HW suppressed VEGF expression, STAT3 phosphorylation and PCNA expression in kidneys of Fe-NTA-treated rats. Consumption with HW decreased the incidence of renal cell carcinoma and suppressed tumor growth in Fe-NTA-treated in rats. In conclusion, drinking with HW attenuated Fe-NTA-induced renal injury and inhibited early tumor promotional events in rats.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/24140467
Growth Suppression of HL60 and L6 Cells by Atomic Hydrogen
ABSTRACT
We previously reported electrolyzed reduced water (ERW) which produced near the cathode by electrolysis has a reductive activity. We also revealed that ERW contains both molecular hydrogen and platinum nanoparticles (Pt nps) derived from platinum-coated titanium electrodes. Pt nps have catalysis activity converting molecular hydrogen to atomic hydrogen. Thus, we regard a solution containing both dissolved hydrogen and Pt nps as a model water of ERW (H2/Pt nps solution), and then we tried to examine the physiological effects of H2/Pt nps solution. To our knowledge, there is no report on physiological effects of H2/Pt nps solution. Here, we report the effects of H2/Pt nps solution on the growth of promyelocytic cell line, HL60 cells and myogenic cell lines, L6 cells. H2/Pt nps solution suppressed cell growth in the presence of both hydrogen and Pt nps in a dose dependent manner. The result of sub-G1 analysis suggests that H2/Pt nps solution induces apoptosis in both HL60 and L6 cells. The labeled Pt nps in HL60 cells were detected in liposome, suggesting Pt nps is incorporated by endocytosis. These results suggest that atomic hydrogen catalyzed by Pt nps induced significant cell growth suppression and atomic hydrogen may be one of new signal of cell function.
Reference-https://link.springer.com/chapter/10.1007%2F978-90-481-3892-0_53#page-1
Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancer
ABSTRACT
Oxidative stress is involved in cancer development. Hydrogen (H2) is a potentantioxidant and exhibits anti-inflammatory and potentially anticancer-like activities.This study aimed to investigate the role of H2incombination with 5-fluorouracil(5-FU) in cancer treatment both in vitro and in vivo using the colon 26 cell line.
The survival rate was determined using the Kaplan–Meier survival test, and cellviability was assessed using cell viability imaging kit and the MTT assay, andactivation of the cell apoptosis pathway (Phosphorylated adenosine monophosphateactivated protein kinase (p-AMPK), Apoptosis-inducing factor (AIF) and Caspase3) were characterized by western blots.
Hydrogen water administration improvedthe survival of mice with colon 26-induced cancer. Furthermore, hydrogen waterenhanced cell apoptosis in cancer cells, resulting in a marked increase in theexpression of p-AMPK, AIF and Caspase 3 in colon 26 cells. Hydrogen water alsoincreased the inhibitory effect of 5-FU on colon 26 cells with spect to cell survivalrate and anticancer functions. Additionally, high-content hydrogen water exhibitedstronger antioxidative and anticancer activity than did the natural hydrogen water.In conclusion, high-content hydrogen water can inhibit colon cancer, particularly incombination with 5-fluorouracil.
Reference-https://peerj.com/articles/859.pdf
Neutral pH hydrogen-enriched electrolyzed water achieves tumor-preferential clonal growth inhibition over normal cells and tumor invasion inhibition concurrently with intracellular oxidant repression
ABSTRACT
The properties and effects of neutral pH hydrogen-enriched electrolyzed water (NHE water) on tumor cells were examined. NHE water diminished hydroxyl radicals as demonstrated by ESR in a cell-free system. Human tongue carcinoma cells HSC-4 were inhibited for either colony formation efficiencies or colony sizes by NHE water without significant inhibition to normal human tongue epithelial-like cells DOK. Furthermore, NHE water caused growth inhibition, cell degeneration, and inhibition of invasion through the reconstituted basement membrane to human fibrosarcoma cells HT-1080. Intracellular oxidants such as hydroperoxides and hydrogen peroxides were scavenged in HSC-4 or HT-1080 cells by NHE water. In the human oral cavity, a dissolved hydrogen concentrations (DH) of NHE water was drastically declined from 1.1 to 0.5 ppm, but settled to 0.3-0.4 ppm until 180 s, upon static holding without gargling. Thus, NHE water was shown to achieve tumor-preferential growth inhibition and tumor invasion together with scavenging of intracellular oxidants, and is expected as a preventive material against tumor progression and invasion.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/19192719
Hydrogen-rich saline reduces delayed neurologic sequelae in experimental carbon monoxide toxicity
ABSTRACT
OBJECTIVE: We investigated the feasibility and efficacy of hydrogen-rich saline therapy on delayed neurologic sequelae in a rat model of severe acute carbon monoxide (CO) poisoning.
DESIGN: Controlled animal study.
SETTING: University research laboratory for Diving Medicine.
SUBJECTS: Sprague-Dawley rats weighing 250 ± 20 g.
INTERVENTIONS: The rats were exposed to 1000 ppm CO in air for 40 min and then to 3000 ppm for another 20 min until they lost consciousness. Rats were intraperitoneal injected with hydrogen-rich saline or normal saline (10 mL/kg) for six times after resuscitation at 0, 12, 24, 36, 48, and 60 hrs, respectively. The rats without CO poisoning were used as normal controls.
MEASUREMENTS AND MAIN RESULTS: Brain tissue inflammation, cell death, and cognitive dysfunction were observed at one week after CO poisoning. Hydrogen-rich saline treatment significantly reduced the level of degraded myelin basic protein, decreased the expression of ionized calcium-binding adapter molecule 1, Iba1, a microglial marker, reduced DNA oxidation, and suppressed proinflammatory cytokine interleukin-1β, interleukin-6, and tumor necrosis factor-α in the cortex and hippocampal tissues when compared with those in normal saline-treated rats. These histologic and biological improvements were accompanied with an improvement in the Morris water maze test.
CONCLUSIONS: This observation demonstrated that hydrogen-rich saline peritoneal injection improves histologic and functional assessment in a rat model of CO encephalopathy. Hydrogen saline has potentials as a novel and alternative therapy for severely CO-poisoned patients with delayed neurologic sequelae. The therapeutic effects of hydrogen-rich saline may be related to antioxidant and anti-inflammatory actions.
References-https://www.ncbi.nlm.nih.gov/pubmed/21200321
Beneficial biological effects and the underlying mechanisms of molecular hydrogen
ABSTRACT
Therapeutic effects of molecular hydrogen for a wide range of disease models and human diseases have been investigated since 2007. A total of 321 original articles have been published from 2007 to June 2015. Most studies have been conducted in Japan, China, and the USA. About three-quarters of the articles show the effects in mice and rats. The number of clinical trials is increasing every year. In most diseases, the effect of hydrogen has been reported with hydrogen water or hydrogen gas, which was followed by confirmation of the effect with hydrogen-rich saline. Hydrogen water is mostly given ad libitum.
Hydrogen gas of less than 4 % is given by inhalation. The effects have been reported in essentially all organs covering 31 disease categories that can be subdivided into 166 disease models, human diseases, treatment-associated pathologies, and pathophysiological conditions of plants with a predominance of oxidative stress-mediated diseases and inflammatory diseases. Specific extinctions of hydroxyl radical and peroxynitrite were initially presented, but the radical-scavenging effect of hydrogen cannot be held solely accountable for its drastic effects. We and others have shown that the effects can be mediated by modulating activities and expressions of various molecules such as Lyn, ERK, p38, JNK, ASK1, Akt, GTP-Rac1, iNOS, Nox1, NF-κB p65, IκBα, STAT3, NFATc1, c-Fos, and ghrelin. Master regulator(s) that drive these modifications, however, remain to be elucidated and are currently being extensively investigated.
Reference-https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4610055/
Molecular Hydrogen as an Emerging Therapeutic Medical Gas for Neurodegenerative and Other Diseases
ABSTRACT
Effects of molecular hydrogen on various diseases have been documented for 63 disease models and human diseases in the past four and a half years. Most studies have been performed on rodents including two models of Parkinson’s disease and three models of Alzheimer’s disease. Prominent effects are observed especially in oxidative stress-mediated diseases including neonatal cerebral hypoxia; Parkinson’s disease; ischemia/reperfusion of spinal cord, heart, lung, liver, kidney, and intestine; transplantation of lung, heart, kidney, and intestine.
Six human diseases have been studied to date: diabetes mellitus type 2, metabolic syndrome, hemodialysis, inflammatory and mitochondrial myopathies, brain stem infarction, and radiation-induced adverse effects. Two enigmas, however, remain to be solved.
First, no dose-response effect is observed. Rodents and humans are able to take a small amount of hydrogen by drinking hydrogen-rich water, but marked effects are observed. Second, intestinal bacteria in humans and rodents produce a large amount of hydrogen, but an addition of a small amount of hydrogen exhibits marked effects. Further studies are required to elucidate molecular bases of prominent hydrogen effects and to determine the optimal frequency, amount, and method of hydrogen administration for each human disease.
Reference- https://www.researchgate.net/publication/227712774_Molecular_Hydrogen_as_an_Emerging_Therapeutic_Medical_Gas_for_Neurodegenerative_and_Other_Diseases
Recent Progress Toward Hydrogen Medicine: Potential of Molecular Hydrogen for Preventive and Therapeutic Applications
ABSTRACT
Persistent oxidative stress is one of the major causes of most lifestyle-related diseases, cancer and the aging process. Acute oxidative stress directly causes serious damage to tissues. Despite the clinical importance of oxidative damage, antioxidants have been of limited therapeutic success. We have proposed that molecular hydrogen (H2) has potential as a “novel” antioxidant in preventive and therapeutic applications [Ohsawa et al., Nat Med. 2007: 13; 688-94].
H2 has a number of advantages as a potential antioxidant: H2 rapidly diffuses into tissues and cells, and it is mild enough neither to disturb metabolic redox reactions nor to affect reactive oxygen species (ROS) that function in cell signaling, thereby, there should be little adverse effects of consuming H2. There are several methods to ingest or consume H2, including inhaling hydrogen gas, drinking H2-dissolved water (hydrogen water), taking a hydrogen bath, injecting H2-dissolved saline (hydrogen saline), dropping hydrogen saline onto the eye, and increasing the production of intestinal H2 by bacteria.
Since the publication of the first H2 paper in Nature Medicine in 2007, the biological effects of H2 have been confirmed by the publication of more than 38 diseases, physiological states and clinical tests in leading biological/medical journals, and several groups have started clinical examinations. Moreover, H2 shows not only effects against oxidative stress, but also various anti-inflammatory and anti-allergic effects. H2 regulates various gene expressions and protein-phosphorylations, though the molecular mechanisms underlying the marked effects of very small amounts of H2 remain elusive.
Reference-https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660246/
Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals
ABSTRACT
Acute oxidative stress induced by ischemia-reperfusion or inflammation causes serious damage to tissues, and persistent oxidative stress is accepted as one of the causes of many common diseases including cancer. We show here that hydrogen (H(2)) has potential as an antioxidant in preventive and therapeutic applications. We induced acute oxidative stress in cultured cells by three independent methods. H(2) selectively reduced the hydroxyl radical, the most cytotoxic of reactive oxygen species (ROS), and effectively protected cells; however, H(2) did not react with other ROS, which possess physiological roles. We used an acute rat model in which oxidative stress damage was induced in the brain by focal ischemia and reperfusion. The inhalation of H(2) gas markedly suppressed brain injury by buffering the effects of oxidative stress. Thus H(2) can be used as an effective antioxidant therapy; owing to its ability to rapidly diffuse across membranes, it can reach and react with cytotoxic ROS and thus protect against oxidative damage.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/17486089
Molecular hydrogen stabilizes atherosclerotic plaque in low-density lipoprotein receptor-knockout mice
ABSTRACT
Hydrogen (H(2)) attenuates the development of atherosclerosis in mouse models. We aimed to examine the effects of H(2) on atherosclerotic plaque stability. Low-density lipoprotein receptor-knockout (LDLR(-/-)) mice fed an atherogenic diet were dosed daily with H(2) and/or simvastatin. In vitro studies were carried out in an oxidized-LDL (ox-LDL)-stimulated macrophage-derived foam cell model treated with or without H(2). H(2) or simvastatin significantly enhanced plaque stability by increasing levels of collagen, as well as reducing macrophage and lipid levels in plaques. The decreased numbers of dendritic cells and increased numbers of regulatory T cells in plaques further supported the stabilizing effect of H(2) or simvastatin. Moreover, H(2) treatment decreased serum ox-LDL level and apoptosis in plaques with concomitant inhibition of endoplasmic reticulum stress (ERS) and reduction of reactive oxygen species (ROS) accumulation in the aorta. In vitro, like the ERS inhibitor 4-phenylbutyric acid, H(2) inhibited ox-LDL- or tunicamycin (an ERS inducer)-induced ERS response and cell apoptosis. In addition, like the ROS scavenger N-acetylcysteine, H(2) inhibited ox-LDL- or Cu(2+) (an ROS inducer)-induced reduction in cell viability and increase in cellular ROS. Also, H(2) increased Nrf2 (NF-E2-related factor-2, an important factor in antioxidant signaling) activation and Nrf2 small interfering RNA abolished the protective effect of H(2) on ox-LDL-induced cellular ROS production. The inhibitory effects of H(2) on the apoptosis of macrophage-derived foam cells, which take effect by suppressing the activation of the ERS pathway and by activating the Nrf2 antioxidant pathway, might lead to an improvement in atherosclerotic plaque stability.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/26117323
H2 inhibits TNF-α-induced lectin-like oxidized LDL receptor-1 expression by inhibiting nuclear factor κB activation in endothelial cells
ABSTRACT
H(2) is a therapeutic antioxidant that can reduce oxidative stress. Oxidized low-density lipoprotein, which plays roles in atherosclerosis, may promote endothelial dysfunction by binding the cell-surface receptor LOX-1. LOX-1 expression can be upregulated by various stimuli, including TNF-α. Thus, we aimed to examine whether the upregulation of LOX-1 by different stimuli could be blocked by H(2) in endothelial cells. H(2) significantly abolished the upregulation of LOX-1 by different stimuli, including TNF-α, at the protein and mRNA levels. The TNF-α-induced upregulation of LOX-1 was also attenuated by the NF-κB inhibitor N-acetyl-L-cysteine. H(2) inhibited the TNF-α-induced activation of NF-κB and the phosphorylation of IκB-α. Furthermore, H(2) inhibited the expression of LOX-1 and the activation of NF-κB in apolipoprotein E knockout mice, an animal model of atherosclerosis. Thus, H(2) probably inhibits cytokine-induced LOX-1 gene expression by suppressing NF-κB activation.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/21544615
Administration of hydrogen-saturated saline decreases plasma low-density lipoprotein cholesterol levels and improves high-density lipoprotein function in high-fat diet-fed hamsters
ABSTRACT
Hydrogen (dihydrogen; H(2)) has an antiatherosclerotic effect in apolipoprotein (apo) E knockout mice. The goals of this study were to further characterize the effects of H(2) on the content, composition, and biological activities of plasma lipoproteins in golden hamsters. Plasma analysis by enzymatic method and fast protein liquid chromatography showed that 4-week intraperitoneal injection of hydrogen-saturated saline remarkably decreased plasma total cholesterol and low-density lipoprotein (LDL) cholesterol levels in high-fat diet-fed hamsters. Sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis of apolipoproteins from ultracentrifugally isolated plasma lipoproteins revealed a marked decrease of apo B100 and apo B48 in LDL. A profound decrease of apo E level in very low-density lipoprotein was also observed. Besides, we determined the functional quality of high-density lipoprotein (HDL) particles isolated from H(2)-treated and control mice. H(2) significantly improved HDL functionality assessed in 2 independent ways, namely, (1) stimulation of cholesterol efflux from macrophage foam cells by measuring HDL-induced [(3)H]cholesterol efflux and (2) protection against LDL oxidation as a measure of Cu(2+)-induced thiobarbituric acid reactive substances formation. Administration of hydrogen-saturated saline decreases plasma LDL cholesterol and apo B levels and improves hyperlipidemia-injured HDL functions, including the capacity of enhancing cellular cholesterol efflux and playing antioxidative properties, in high-fat diet-fed hamsters.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/22153840
The evolution of molecular hydrogen: a noteworthy potential therapy with clinical significance
ABSTRACT
Studies on molecular hydrogen have evolved tremendously from its humble beginnings and have continued to change throughout the years. Hydrogen is extremely unique since it has the capability to act at the cellular level. Hydrogen is qualified to cross the blood brain barrier, to enter the mitochondria, and even has the ability to translocate to the nucleus under certain conditions.
Once in these ideal locations of the cell, previous studies have shown that hydrogen exerts antioxidant, anti-apoptotic, anti-inflammatory, and cytoprotective properties that are beneficial to the cell. Hydrogen is most commonly applied as a gas, water, saline, and can be applied in a variety of other mediums.
There are also few side effects involving hydrogen, thus making hydrogen a perfect medical gas candidate for the convention of novel therapeutic strategies against cardiovascular, cerebrovascular, cancer, metabolic, and respiratory diseases and disorders. Although hydrogen appears to be faultless at times, there still are several deficiencies or snares that need to be investigated by future studies. This review article seeks to delve and comprehensively analyze the research and experiments that alludes to molecular hydrogen being a novel therapeutic treatment that medicine desperately needs.
Reference-https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660246/
Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome-an open label pilot study
ABSTRACT
Metabolic syndrome is characterized by cardiometabolic risk factors that include obesity, insulin resistance, hypertension and dyslipidemia. Oxidative stress is known to play a major role in the pathogenesis of metabolic syndrome. The objective of this study was to examine the effectiveness of hydrogen rich water (1.5-2 L/day) in an open label, 8-week study on 20 subjects with potential metabolic syndrome.
Hydrogen rich water was produced, by placing a metallic magnesium stick into drinking water (hydrogen concentration; 0.55-0.65 mM), by the following chemical reaction; Mg + 2H(2)O –> Mg (OH)(2) + H(2). The consumption of hydrogen rich water for 8 weeks resulted in a 39% increase (p<0.05) in antioxidant enzyme superoxide dismutase (SOD) and a 43% decrease (p<0.05) in thiobarbituric acid reactive substances (TBARS) in urine.
Further, subjects demonstrated an 8% increase in high density lipoprotein (HDL)-cholesterol and a 13% decrease in total cholesterol/HDL-cholesterol from baseline to week 4. There was no change in fasting glucose levels during the 8 week study. In conclusion, drinking hydrogen rich water represents a potentially novel therapeutic and preventive strategy for metabolic syndrome. The portable magnesium stick was a safe, easy and effective method of delivering hydrogen rich water for daily consumption by participants in the study.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/20216947/
Hydrogen Activates ATP-Binding Cassette Transporter A1-Dependent Efflux Ex Vivo and Improves High-Density Lipoprotein Function in Patients With Hypercholesterolemia: A Double-Blinded, Randomized, and Placebo-Controlled Trial
ABSTRACT
CONTEXT: We have found that hydrogen (dihydrogen [H2]) decreases plasma low-density lipoprotein (LDL) cholesterol levels and improves high-density lipoprotein (HDL) function in patients with potential metabolic syndrome in a before-after self-controlled study.
OBJECTIVE: The purpose of this study was to further characterize the effects of H2-rich water (0.9 L/day) on the content, composition, and biological activities of plasma lipoproteins on patients with hypercholesterolemia and their underlying mechanisms in a double-blinded, randomized, and placebo-controlled trial.
DESIGN: This was a case-control study.
SETTING: The setting was the Zhoudian community, Tai’an, China.
PATIENTS: A total of 68 patients with untreated isolated hypercholesterolemia were randomly allocated to either drinking H2-rich water (n = 34) or placebo water (n = 34) for 10 weeks.
RESULTS: HDL isolated from the H2 group showed an increased ability to promote the ATP-binding cassette transporter A1-mediated cholesterol efflux ex vivo. Plasma pre-β-HDL levels were up-regulated although there were no changes in plasma HDL-cholesterol levels. Moreover, other HDL functions, assessed in protection against LDL oxidation, inhibition of oxidized-LDL-induced inflammation, and protection of endothelial cells from oxidized-LDL-induced apoptosis, were all significantly improved by H2 treatment. In addition, H2 treatment increased the effective rate in down-regulating plasma levels of total cholesterol (47.06% vs 17.65%) and LDL cholesterol (47.06% vs 23.53%). Western blot analysis revealed a marked decrease in apolipoprotein B100 and an increase in apolipoprotein M in plasma of the H2 group. Finally H2 treatment resulted in a significant reduction in the levels of several inflammatory and oxidative stress indicators in whole plasma and HDL particles.
CONCLUSIONS: H2 activates ATP-binding cassette transporter A1-dependent efflux, enhances HDL antiatherosclerotic functions, and has beneficial lipid-lowering effects. The present findings highlight the potential role of H2 in the regression of hypercholesterolemia and atherosclerosis.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/25978109
Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome
ABSTRACT
We have found that hydrogen (dihydrogen; H2) has beneficial lipid-lowering effects in high-fat diet-fed Syrian golden hamsters. The objective of this study was to characterize the effects of H2-rich water (0.9-1.0 l/day) on the content, composition, and biological activities of serum lipoproteins on 20 patients with potential metabolic syndrome.
Serum analysis showed that consumption of H2-rich water for 10 weeks resulted in decreased serum total-cholesterol (TC) and LDL-cholesterol (LDL-C) levels. Western blot analysis revealed a marked decrease of apolipoprotein (apo)B100 and apoE in serum. In addition, we found H2 significantly improved HDL functionality assessed in four independent ways, namely, i) protection against LDL oxidation, ii) inhibition of tumor necrosis factor (TNF)-α-induced monocyte adhesion to endothelial cells, iii) stimulation of cholesterol efflux from macrophage foam cells, and iv) protection of endothelial cells from TNF-α-induced apoptosis.
Further, we found consumption of H2-rich water resulted in an increase in antioxidant enzyme superoxide dismutase and a decrease in thiobarbituric acid-reactive substances in whole serum and LDL. In conclusion, supplementation with H2-rich water seems to decrease serum LDL-C and apoB levels, improve dyslipidemia-injured HDL functions, and reduce oxidative stress, and it may have a beneficial role in prevention of potential metabolic syndrome.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/23610159
Inhalation of hydrogen gas attenuates cognitive impairment in transient cerebral ischemia via inhibition of oxidative stress
ABSTRACT
OBJECTIVE: To investigate the effects of inhalation of hydrogen gas on cognitive impairment induced by transient cerebral ischemia and its potential mechanism.
METHODS: Two-vessel occlusion rat model was used to produce 10-minute transient global cerebral ischemia. One hundred and twenty male Wistar rats were randomly divided into sham, sham+H(2), ischemia, and ischemia+H(2) groups (n = 30 each group). Inhalation of 2% hydrogen gas was performed immediately at the end of operation and lasted for 3 hours. Cognitive function of rats was evaluated via Morris water maze. Neuronal damage in the CA1 region was quantified according to their morphological changes revealed by hematoxylin-eosin staining. The levels of oxidative stress products malondialdehyde (MDA) and 8-iso-prostaglandin F2alpha, and the activities of anti-oxidative enzymes catalase and superoxide dismutase were measured to investigate the effects of inhalation of hydrogen gas on oxidative stress.
RESULTS: Inhalation of hydrogen gas decreased significantly the average latency of the ischemic rats in finding hidden platform and elongated markedly their retention in the target quadrant. The neuronal density 3·3±2·1 cells/mm in CA1 region of the ischemic rats increased to 21·7±2·6 cells/mm after they were treated with hydrogen gas. Moreover, hydrogen gas made higher levels of MDA and 8-iso-PGF2α in the ischemic rats attenuate to 3·2±0·2, 3·5±0·5, 3·4±0·3 and 26·4±2·3, 28·2±2·6, 26·8±2·1 at reperfusion 4, 24, and 72 hours, respectively (P<0·01 versus ischemia group at each indicated time). By contrast, the activities of superoxide dismutase and catalase damaged by ischemia/reperfusion recovered to 129·7±14·8, 100·5±12·2 and 11·4±0·8, 9·6±1·1 at reperfusion 24 and 72 hours, respectively (P<0·01 versus ischemia group at each indicated time).
CONCLUSION: Inhalation of hydrogen gas could attenuate cognitive impairment in the ischemic rats. This protection is associated with decreased neuronal death in CA1 region and inhibition of oxidative stress.
References-https://www.ncbi.nlm.nih.gov/pubmed/22333294
Drinking Hydrogen Water Ameliorated Cognitive Impairment in Senescence-Accelerated Mice
ABSTRACT
Hydrogen has been reported to have neuron protective effects due to its antioxidant properties, but the effects of hydrogen on cognitive impairment due to senescence-related brain alterations and the underlying mechanisms have not been characterized. In this study, we investigated the efficacies of drinking hydrogen water for prevention of spatial memory decline and age-related brain alterations using senescence-accelerated prone mouse 8 (SAMP8), which exhibits early aging syndromes including declining learning ability and memory. However, treatment with hydrogen water for 30 days prevented age-related declines in cognitive ability seen in SAMP8 as assessed by a water maze test and was associated with increased brain serotonin levels and elevated serum antioxidant activity. In addition, drinking hydrogen water for 18 weeks inhibited neurodegeneration in hippocampus, while marked loss of neurons was noted in control, aged brains of mice receiving regular water. On the basis of our results, hydrogen water merits further investigation for possible therapeutic/preventative use for age-related cognitive disorders.
References-https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2872234/
Oxidants and anti-oxidants status in acne vulgaris patients with varying severity
Addressing Free Radical Oxidationin Acne Vulgari
Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in mice Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in miceHydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen–water enhances5-fluorouracil-induced inhibition of colon cancer Hydrogen–water enhances5-fluorouracil-induced inhibition ofcolon cancerHydrogen–water enhances5-fluorouracil-induced inhibition ofcolon cancerTop of Form
ABSTRACT
Acne vulgaris is a common dermatological disorder with a multifactorial pathogenesis. Oxidative status has been implicated in the pathogenesis of several skin diseases, including acne. This study was aimed to investigate the levels of oxidative stress biomarkers in acne vulgaris patients with varying severities. The study involved 156 patients with acne and 46 healthy human controls.
Based on clinical examination, patients were grouped into 3 subgroups as follows: mild, moderate, and severe acne. Oxidative stress was examined by measuring plasma levels of catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (TAC), and malondialdehyde (MDA). Plasma levels of MDA in acne patients were significantly higher as compared with that of the controls, whereas activities of the antioxidant enzymes SOD and CAT were lower. Moreover, TAC was also low in acne patients as compared with that of the controls. Higher MDA levels in the severe acne subgroup as compared with that of the mild and moderate subgroups were also observed. Furthermore, in the severe acne subgroup, a significant negative correlation was observed between MDA and CAT levels. The data suggests that oxidative stress plays a key role in acne progress and may be employed as a biomarker index to assess the disease’s activity and to monitor its treatment.
References-https://www.ncbi.nlm.nih.gov/pubmed/24795060
Consumption of molecular hydrogen prevents the stress-induced impairments in hippocampus-dependent learning tasks during chronic physical restraint in mice
ABSTRACT
We have reported that hydrogen (H(2)) acts as an efficient antioxidant by gaseous rapid diffusion. When water saturated with hydrogen (hydrogen water) was placed into the stomach of a rat, hydrogen was detected at several microM level in blood. Because hydrogen gas is unsuitable for continuous consumption, we investigated using mice whether drinking hydrogen water ad libitum, instead of inhaling hydrogen gas, prevents cognitive impairment by reducing oxidative stress.
Chronic physical restraint stress to mice enhanced levels of oxidative stress markers, malondialdehyde and 4-hydroxy-2-nonenal, in the brain, and impaired learning and memory, as judged by three different methods: passive avoidance learning, object recognition task, and the Morris water maze.
Consumption of hydrogen water ad libitum throughout the whole period suppressed the increase in the oxidative stress markers and prevented cognitive impairment, as judged by all three methods, whereas hydrogen water did not improve cognitive ability when no stress was provided. Neural proliferation in the dentate gyrus of the hippocampus was suppressed by restraint stress, as observed by 5-bromo-2′-deoxyuridine incorporation and Ki-67 immunostaining, proliferation markers. The consumption of hydrogen water ameliorated the reduced proliferation although the mechanistic link between the hydrogen-dependent changes in neurogenesis and cognitive impairments remains unclear. Thus, continuous consumption of hydrogen water reduces oxidative stress in the brain, and prevents the stress-induced decline in learning and memory caused by chronic physical restraint. Hydrogen water may be applicable for preventive use in cognitive or other neuronal disorders.
References-https://www.ncbi.nlm.nih.gov/pubmed/18563058
Hydrogen-rich saline prevents early neurovascular dysfunction resulting from inhibition of oxidative stress in STZ-diabetic rats
ABSTRACT
PURPOSE: Diabetic retinopathy (DR) is characterized by increased oxidative and nitrosative stress, both of which lead to neurotoxicity and vascular permeability. Previous studies on a variety of organs indicate that hydrogen-rich saline not only has considerable antioxidant and anti-inflammatory properties, but also suppresses oxidative stress-induced injury. In the present study, we assessed the effects of hydrogen-rich saline on neurovascular dysfunction and oxidative stress in an animal model (rat) of DR.
MATERIALS AND METHODS: Male Sprague-Dawley rats with streptozotocin (STZ)-induced diabetes mellitus (DM) were injected intraperitoneally with 5 ml/kg hydrogen-saturated (experimental) or plain (control) saline daily for one month. Visual function and blood-retinal barrier (BRB) integrity were evaluated by electroretinography (ERG) and bovine serum albumin (BSA)-fluorescence, respectively. Histological changes in the inner retina were assessed by light microscopy. Biomarkers of oxidative stress, including 4-hydroxynonenal (4-HNE) and 8-hydroxy-2-deoxyguanosine (8-OH-dG), and antioxidant enzymes, including superoxide dismutase, glutathione peroxidase, glutathione reductase and glutathione transferase, were evaluated by ELISA. Synaptophysin and brain-derived neurotrophic factor (BDNF) levels were measured by immunoblotting.
RESULTS: STZ-diabetic rats were marked by clearly reduced b-wave amplitudes and oscillatory potentials, DM-related BRB breakdown and histological changes in the inner retina, all of which were suppressed following treatment with hydrogen-rich saline. Furthermore, hydrogen-rich saline reduced oxidative stress, increased antioxidant enzyme activities and preserved synaptophysin and BDNF levels in the diabetic rat retina.
CONCLUSIONS: Based on its inhibition of oxidative stress and up-regulation of anti-oxidative enzymes, we conclude that hydrogen-rich saline is a potentially valuable therapeutic modality for the treatment of DR.
References-https://www.ncbi.nlm.nih.gov/pubmed/23252792
Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury
ABSTRACT
Hydrogen can relieve tissue-damaging oxidative stress, inflammation and apoptosis. Injection of hydrogen-rich saline is an effective method for transporting molecular hydrogen. We hypothesized that hydrogen-rich saline would promote the repair of spinal cord injury induced by Allen’s method in rats. At 0.5, 1, 2, 4, 8, 12 and 24 hours after injury, then once daily for 2 weeks, 0.25 mL/kg hydrogen-rich saline was infused into the subarachnoid space through a catheter. Results at 24 hours, 48 hours, 1 week and 2 weeks after injury showed that hydrogen-rich saline markedly reduced cell death, inflammatory cell infiltration, serum malondialdehyde content, and caspase-3 immunoreactivity, elevated serum superoxide dismutase activity and calcitonin gene-related peptide immunoreactivity, and improved motor function in the hindlimb. The present study confirms that hydrogen-rich saline injected within 2 weeks of injury effectively contributes to the repair of spinal cord injury in the acute stage.
Reference-http://www.nrronline.org/article.asp?issn=1673-5374;year=2015;volume=10;issue=6;spage=958;epage=964;aulast=Wang#top
Hydrogen-rich saline protects against spinal cord injury in rats
ABSTRACT
In the present study, we examined the mechanisms of hydrogen-rich saline, a reported therapeutic antioxidant, in the treatment of acute spinal cord contusion injury. Male Sprague-Dawley rats were used to produce a standardized model of contuses spinal cord injury (125 kdyn force). Hydrogen-rich saline was injected intraperitoneally (5 ml/kg) immediately, and at 24 and 48 h after injury. All rats were sacrificed at 72 h after spinal cord injury (SCI). Apoptotic cell death, oxidative stress, inflammation, level of Brain derived neurotrophic factor (BDNF) were evaluated. In addition, locomotor behavior was assessed using the Basso, Beattice and Bresnahan (BBB) scale. We observed that administration of hydrogen-rich saline decreased the number of apoptotic cells, suppressed oxidative stress, and improved locomotor functions. Hydrogen-rich saline increased the release of BDNF. In conclusion, hydrogen-rich saline reduced acute spinal cord contusion injury, possibly by reduction of oxidative stress and elevation of BDNF.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/20354783
Molecular Hydrogen in Drinking Water Protects against Neurodegenerative Changes Induced by Traumatic Brain
ABSTRACT
Traumatic brain injury (TBI) in its various forms has emerged as a major problem for modern society. Acute TBI can transform into a chronic condition and be a risk factor for neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases, probably through induction of oxidative stress and neuro inflammation.
Here, we examined the ability of the antioxidant molecular hydrogen given in drinking water (molecular hydrogen water; mHW) to alter the acute changesinduced by controlled cortical impact (CCI), a commonly used experimental model of TBI. We found that mHW reversed CCI inducededema by about half, completely blocked pathological tau expression, accentuated an early increase seen inseveral cytokines but attenuated that increase by day 7, reversed changes seen in the protein levels of aquaporin-4, HIF-1,MMP-2, and MMP-9, but not for amyloid beta peptide 1–40 or 1–42.
Treatment with mHW also reversed the increase seen 4 h after CCI in gene expression related to oxidation/carbohydrate metabolism, cytokine release, leukocyte or cell migration, cytokine transport, ATP and nucleotide binding. Finally, we found that mHW preserved or increased ATP levels and propose a new mechanism for mHW, that of ATP production through the Jagendorf reaction. These results show that molecular hydrogen given in drinking water reverses many of the sequelae of CCI and suggests that it could be an easily administered, highly effective treatment for TBI.
Reference-https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0108034&type=printable
The Effects of Hydrogen-Rich Saline on the Contractile and Structural Changes of Intestine Induced by Ischemia-Reperfusion in Rats
ABSTRACT
Background
Hydrogen gas was reported to reduce reactive oxygen species and alleviate cerebral, myocardial and hepatic ischemia/reperfusion (I/R) injuries. This paper studied the effect of hydrogen-rich saline, which was easier for clinical application, on the intestinal I/R injury. Model of intestinal I/R injury was induced in male Sprague-Dawley rats. Physiological saline, hydrogen-rich saline or nitrogen-rich saline (5 ml/kg) was administered via intravenous infusion at 10 min before reperfusion, respectively. The intestine damage was detected microscopically and was assessed by Chiu score system after I/R injury. In addition, serum DAO activity, TNF-α, IL-1β and IL-6 levels, tissue MDA, protein carbonyl and MPO activity were all increased significantly by I/R injury. Hydrogen-rich saline reduced these markers and relieved morphological intestinal injury, while no significant reduction was observed in the nitrogen-rich saline-treated animals. In conclusion, hydrogen-rich saline protected the small intestine against I/R injury, possibly by reduction of inflammation and oxidative stress.
Reference-https://www.journalofsurgicalresearch.com/article/S0022-4804%2809%2900419-3/fulltext
Hydrogen-rich saline protects against intestinal ischemia/reperfusion injury in rats
ABSTRACT
Hydrogen gas was reported to reduce reactive oxygen species and alleviate cerebral, myocardial and hepatic ischemia/reperfusion (I/R) injuries. This paper studied the effect of hydrogen-rich saline, which was easier for clinical application, on the intestinal I/R injury. Model of intestinal I/R injury was induced in male Sprague-Dawley rats. Physiological saline, hydrogen-rich saline or nitrogen-rich saline (5 ml/kg) was administered via intravenous infusion at 10 min before reperfusion, respectively. The intestine damage was detected microscopically and was assessed by Chiu score system after I/R injury. In addition, serum DAO activity, TNF-α, IL-1β and IL-6 levels, tissue MDA, protein carbonyl and MPO activity were all increased significantly by I/R injury. Hydrogen-rich saline reduced these markers and relieved morphological intestinal injury, while no significant reduction was observed in the nitrogen-rich saline-treated animals. In conclusion, hydrogen-rich saline protected the small intestine against I/R injury, possibly by reduction of inflammation and oxidative stress.
Reference-https://www.sciencedirect.com/science/article/pii/S0006291X09010614
Hydrogen mediates suppression of colon inflammation induced by dextran sodium sulfate
ABSTRACT
By its antioxidant effect, molecular hydrogen gas (H2) was reported to protect organs from tissue damage induced by ischemia reperfusion. To evaluate its anti-inflammatory effects, we established a mouse model of human inflammatory bowel disease (IBD) by supplying mice with water containing (1) dextran sodium sulfate (DSS) (5%), (2) DSS (5%) and H2, or (3) H2 only ad libitum up to 7 days. At day-7, DSS-induced pathogenic outcomes including, loss of body weight, increase of colitis score, pathogenic shortening of colon length, elevated level of IL-12, TNF-α and IL-1β in colon lesion, were significantly suppressed by the addition of H2 to DSS solution. Histological analysis also revealed that the DSS-mediated colonic tissue destruction accompanied by macrophage infiltration was remarkably suppressed by H2. Therefore, the present study indicated that H2 can prevent the development of DSS-induced colitis in mice.
Reference-https://www.sciencedirect.com/science/article/pii/S0006291X09010614
Protective effects of hydrogen-rich saline on necrotizing enterocolitis in neonatal rats
ABSTRACT
Purpose: The aim of this study was to test the hypothesis that hydrogen-rich saline (HRS) might have protective effects on the development of necrotizing enterocolitis (NEC) in a neonatal rat model.
Methods: NEC was induced in male newborn Sprague–Dawley rats by formula feeding, exposure to asphyxia and cold stress. Sixty-four rat pups were divided randomly into four groups: C+NS (n=11), C+H2 (n=11), NEC+NS (n=20), and NEC+H2 (n=22). Rats in the former two groups were mother-fed. Pups received intra-peritoneal injection of HRS (10 ml/kg, 10 min before asphyxia stress twice a day) or the same dose of normal saline. Rats were monitored until 96 h after birth. Body weight, histological NEC score, survival time, malondialdehyde, antioxidant capacity, inflammatory mediators, and mucosal integrity were assessed.
Results: HRS treatment maintained the body weight, reduced the incidence of NEC from 85% (17/20) to 54.5% (12/22), increased the survival rate from 25% (5/20) to 68.2% (15/22), and attenuated the severity of NEC. In addition, HRS inhibited the mRNA expression of pro-inflammatory mediators (inducible nitric oxide synthase, tumor necrosis factor-α, and interleukin-6), down-regulated lipid peroxidation, enhanced total antioxidant capacity, and prevented the increase of diamine oxidase in serum. However, no significant influence of HRS on the interleukin-10 mRNA expression was observed.
Conclusions: HRS showed beneficial effects on neonatal rats with NEC via decreasing oxidative stress, increasing antioxidant capacity, suppressing inflammation, and preserving mucosal integrity.
Reference-https://www.jpedsurg.org/article/S0022-3468%2812%2900954-2/abstract
Protective effects of hydrogen-rich saline on ulcerative colitis rat model
ABSTRACT
BACKGROUND: Ulcerative colitis (UC) is associated with enhanced production of reactive oxygen species and altered angiogenesis. Molecular hydrogen has been documented as a novel antioxidant to treat various reactive oxygen species-related diseases. The present study aimed to investigate the effects of hydrogen on UC using a rat model.
MATERIALS AND METHODS: UC in rats was induced with intracolonically administrated acetic acid. Hydrogen was supplied through intraperitoneal injection of 10 or 20 mL/kg hydrogen-rich saline. The hydrogen treatment was performed once every 2 d and lasted 2 wk. The stool consistency and weight loss were used to evaluate UC development. Colonic mucosal damage at the end of the experiment was scored using the macroscopic and microscopic observations. Vascular endothelial growth factor expression in the colonic mucosa was determined using immunohistochemistry.
RESULTS: The administration of acetic acid induced acute rat UC, as indicated by diarrhea, weight loss, and colonic mucosal damage. Treatment with hydrogen-rich saline reduced the weight loss and diarrhea and alleviated the colonic mucosal damage in the UC rats. In addition, the expression of vascular endothelial growth factor in the UC rats increased and could be inhibited by hydrogen treatment.
CONCLUSIONS: Antioxidative hydrogen-rich saline effectively protected the rats from UC, which might be, at least in part, because of inhibition of vascular endothelial growth factor.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/23773716
Hydrogen as a Selective Antioxidant: A Review of Clinical and Experimental Studies
ABSTRACT
Oxidative stress is implicated in the pathogenesis of many diseases; however, currently used antioxidants have a high toxicity that constrains administration to a narrow window of therapeutic dosage. There is a clear need for more effective and safer antioxidants. Diatomic hydrogen (H2) was proposed as a novel antioxidant that selectively reduces levels of toxic reactive-oxygen species. Recently, many studies have reported that H2 (inhaled or orally ingested, typically as approximately 0.8 mM H2-saturated water), can exert beneficial effects in diverse animal models of ischaemia–reperfusion injury, and inflammatory and neurological disease. In the clinic, oral administration of H2-saturated water is reported to improve lipid and glucose metabolism in subjects with diabetes or impaired glucose tolerance; promising results have also been obtained in reducing inflammation in haemodialysis patients and treating metabolic syndrome. These studies suggest H2 has selective antioxidant properties, and can exert antiapoptotic, anti-inflammatory and antiallergy effects. This review summarizes recent research findings and mechanisms concerning the therapeutic potential of H2.
Reference-https://journals.sagepub.com/doi/abs/10.1177/147323001003800602
Protective effects of hydrogen-rich saline in a rat model of traumatic brain injury via reducing oxidative stress
ABSTRACT
BACKGROUND: Hydrogen gas (H(2)) has been considered as a novel antioxidant to selectively reduce the toxic reactive oxygen species (ROS) such as hydroxyl radical (•OH) without affecting the other signal ROS. Our recent study shows that H(2) inhalation is beneficial to traumatic brain injury (TBI) via reducing oxidative stress. In contrast to H(2), hydrogen-rich saline (HS) may be more suitable for clinical application. The present study was designed to investigate whether HS has a protective effect against TBI via reducing oxidative stress in rats.
METHODS: TBI model was induced by controlled cortical impact injury. Different dosages of HS were intraperitoneally administered at 5 min after TBI operation. We then measured the brain edema, blood-brain barrier (BBB) breakdown, neurological dysfunction and injury volume in all animals. In addition, the oxidative products and antioxidant enzymes in brain tissues were detected.
RESULTS: TBI-challenged rats exhibited significant brain injuries characterized by the increase of BBB permeability, brain edema, and lesion volume as well as neurological dysfunction, which were dose-dependently ameliorated by HS treatment. Moreover, we found that HS treatment increased the endogenous antioxidant enzymatic activities and decreased the oxidative product levels in brain tissues of TBI-challenged rats.
CONCLUSION: Hydrogen-rich saline can exert a protective effect against TBI via reducing oxidative stress. Molecular hydrogen may be a more effective therapeutic strategy for TBI patients.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/22475349
Beneficial effects of hydrogen gas in a rat model of traumatic brain injury via reducing oxidative stress
ABSTRACT
Traumatic brain injury (TBI) is a leading cause of mortality and disability among the young population. It has been shown that hydrogen gas (H(2)) exerts a therapeutic antioxidant activity by selectively reducing hydroxyl radical (OH, the most cytotoxic ROS). Recently, we have found that H(2) inhalation significantly improved the survival rate and organ damage of septic mice. In the present study, we investigated the effectiveness of H(2) therapy on brain edema, blood-brain barrier (BBB) breakdown, neurological dysfunction and injury volume in TBI-challenged rats. In addition, we investigated the effects of H(2) treatment on the changes of oxidative products and antioxidant enzymes in brain tissue of TBI-challenged rats. Hydrogen treatment was given by exposure to 2% H(2) from 5 min to 5h after sham or TBI operation, respectively. Here, we found that TBI-challenged rats showed significant brain injuries characterized by the increase of BBB permeability, brain edema and lesion volume as well as neurological dysfunction, which was significantly attenuated by 2% H(2) treatment. In addition, we found that the decrease of oxidative products and the increase of endogenous antioxidant enzymatic activities in the brain tissue may be associated with the protective effects of H(2) treatment in TBI-challenged rats. The present study supports that H(2) inhalation may be a more effective therapeutic strategy for patients with TBI.
Reference-https://www.ncbi.nlm.nih.gov/pubmed/20654594
Chronic neurodegeneration after traumatic brain injury: Alzheimer disease, chronic traumatic encephalopathy, or persistent neuroinflammation
ABSTRACT
It has long been suggested that prior traumatic brain injury (TBI) increases the subsequent incidence of chronic neurodegenerative disorders, including Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis. Among these, the association with Alzheimer disease has the strongest support.
There is also a long-recognized association between repeated concussive insults and progressive cognitive decline or other neuropsychiatric abnormalities. The latter was first described in boxers as dementia pugilistica, and has received widespread recent attention in contact sports such as professional American football. The term chronic traumatic encephalopathy was coined to attempt to define a “specific” entity marked by neurobehavioral changes and the extensive deposition of phosphorylated tau protein. Nearly lost in the discussions of post-traumatic neurodegeneration after traumatic brain injury has been the role of sustained neuroinflammation, even though this association has been well established pathologically since the 1950s, and is strongly supported by subsequent preclinical and clinical studies. Manifested by extensive microglial and astroglial activation, such chronic traumatic brain inflammation may be the most important cause of post-traumatic neurodegeneration in terms of prevalence. Critically, emerging preclinical studies indicate that persistent neuroinflammation and associated neurodegeneration may be treatable long after the initiating insult(s).
Reference-https://www.trusii.info/h2-research-studies
Molecular Hydrogen in Drinking Water Protects against Neurodegenerative Changes Induced by Traumatic Brain Injury
ABSTRACT
Traumatic brain injury (TBI) in its various forms has emerged as a major problem for modern society. Acute TBI can transform into a chronic condition and be a risk factor for neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases, probably through induction of oxidative stress and neuroinflammation.
Here, we examined the ability of the antioxidant molecular hydrogen given in drinking water (molecular hydrogen water; mHW) to alter the acute changes induced by controlled cortical impact (CCI), a commonly used experimental model of TBI. We found that mHW reversed CCI-induced edema by about half, completely blocked pathological tau expression, accentuated an early increase seen in several cytokines but attenuated that increase by day 7, reversed changes seen in the protein levels of aquaporin-4, HIF-1, MMP-2, and MMP-9, but not for amyloid beta peptide 1–40 or 1–42.
Treatment with mHW also reversed the increase seen 4 h after CCI in gene expression related to oxidation/carbohydrate metabolism, cytokine release, leukocyte or cell migration, cytokine transport, ATP and nucleotide binding. Finally, we found that mHW preserved or increased ATP levels and propose a new mechanism for mHW, that of ATP production through the Jagendorf reaction. These results show that molecular hydrogen given in drinking water reverses many of the sequelae of CCI and suggests that it could be an easily administered, highly effective treatment for TBI.
Reference-https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0108034
Inhalation of hydrogen gas attenuates brain injury in mice with cecal ligation and puncture via inhibiting neuroinflammation, oxidative stress and neuronal apoptosis.
ABSTRACT
During the development of sepsis, the complication in central nervous system (CNS), appearing early and frequently relative to other systems, can obviously increase the mortality of sepsis. Moreover, sepsis survivors also accompany long-term cognitive dysfunction, while the ultimate causes and effective therapeutic strategies of brain injury in sepsis are still not fully clear. We designed this study to investigate the effects of 2% hydrogen gas (H2) on brain injury in a mouse model of sepsis. Male ICR mice were underwent cecal ligation and puncture (CLP) or sham operation. 2% H2 was inhaled for 60min beginning at both 1 and 6h after sham or CLP operation, respectively. H2 concentration in arterial blood, venous blood and brain tissue was detected after H2 inhalation separately. The survival rate was observed and recorded within 7 days after sham or CLP operation. The histopathologic changes and neuronal apoptosis were observed in hippocampus by Nissl staining and TUNEL assay. The permeability of brain-blood barrier (BBB), brain water content, inflammatory cytokines, activities of antioxidant enzymes (SOD and CAT) and oxidative products (MDA and 8-iso-PGF2α) in serum and hippocampus were detected at 24h after sham or CLP operation. The expressions of nucleus and total nuclear factor erythroid 2-related factor 2 (Nrf2) and cytoplasmic heme oxygenase-1(HO-1) in hippocampus were measured at 24h after sham or CLP operation. We assessed their cognitive function via Y-maze and Fear Conditioning test on day 3, 5, 7 and 14 after operation. H2 treatment markedly improved the survival rate and cognitive dysfunction of septic mice. CLP mice showed obvious brain injury characterized by aggravated pathological damage, BBB disruption and brain edema at 24h after CLP operation, which was markedly alleviated by 2% H2 treatment. Furthermore, we found that the beneficial effects of H2 on brain injury in septic mice were linked to the decreased levels of inflammatory cytokines and oxidative products and the increased activities of antioxidant enzymes in serum and hippocampus. In addition, 2% H2 inhalation promoted the expression and transposition of Nrf2 and the expression of HO-1 to mitigate brain injury in sepsis. Thus, the inhalation of hydrogen gas may be a promising therapeutic strategy to relieve brain injury in sepsis.
References–https://www.ncbi.nlm.nih.gov/pubmed/25251596
Hydrogen-rich saline reduces oxidative stress and inflammation by inhibit of JNK and NF-κB activation in a rat model of amyloid-beta-induced Alzheimer’s disease
ABSTRACT
This study is to examine if hydrogen-rich saline reduced amyloid-beta (Aβ) induced neural inflammation and oxidative stress in a rat model by attenuation of activation of JNK and NF-κB. Sprague-Dawley male rats (n=18, 280-330 g) were divided into three groups, sham operated, Aβ1-42 injected and Aβ1-42 plus hydrogen-rich saline treated animals. Hydrogen-rich saline (5 ml/kg, i.p., daily) was injected for 10 days after intraventricular injection of Aβ1-42. The levels of IL-1β were assessed by ELISA analysis, 8-OH-dG by immunohistochemistry in the brain slides, and JNK and NF-κB by immunohistochemistry and western blotting. After Aβ1-42 injection, the level of IL-1β, 8-OH-dG, JNK and NF-κB all increased in brain tissues, while hydrogen-rich saline treatment decreased the level of IL-1β, 8-OH-dG and the activation of JNK and NF-κB. In conclusion, hydrogen-rich saline prevented Aβ-induced neuroinflammation and oxidative stress, possibly by attenuation of activation of c-Jun NH₂-terminal kinase (JNK) and nuclear factor-κB (NF-κB) in this rat model.
References–https://www.ncbi.nlm.nih.gov/pubmed/21238541
Molecular hydrogen reduces LPS-induced neuroinflammation and promotes recovery from sickness behaviour in mice
ABSTRACT
Molecular hydrogen has been shown to have neuroprotective effects in mouse models of acute neurodegeneration. The effect was suggested to be mediated by its free-radical scavenger properties. However, it has been shown recently that molecular hydrogen alters gene expression and protein phosphorylation. The aim of this study was to test whether chronic ad libitum consumption of molecular hydrogen-enriched electrochemically reduced water (H-ERW) improves the outcome of lipopolysaccharide (LPS)-induced neuroinflammation. Seven days after the initiation of H-ERW treatment, C57Bl/6 mice received a single injection of LPS (0.33 mg/kg i.p.) or an equivalent volume of vehicle. The LPS-induced sickness behaviour was assessed 2 h after the injection, and recovery was assessed by monitoring the spontaneous locomotor activity in the homecage for 72 h after the administration of LPS. The mice were killed in the acute or recovery phase, and the expression of pro- and antiinflammatory cytokines in the hippocampus was assessed by real-time PCR. We found that molecular hydrogen reduces the LPS-induced sickness behaviour and promotes recovery. These effects are associated with a shift towards anti-inflammatory gene expression profile at baseline (downregulation of TNF- α and upregulation of IL-10). In addition, molecular hydrogen increases the amplitude, but shortens the duration and promotes the extinction of neuroinflammation. Consistently, molecular hydrogen modulates the activation and gene expression in a similar fashion in immortalized murine microglia (BV-2 cell line), suggesting that the effects observed in vivo may involve the modulation of microglial activation. Taken together, our data point to the regulation of cytokine expression being an additional critical mechanism underlying the beneficial effects of molecular hydrogen.
References–https://www.ncbi.nlm.nih.gov/pubmed/22860058
Hydrogen-rich saline improves memory function in a rat model of amyloid-beta-induced Alzheimer’s disease by reduction of oxidative stress
ABSTRACT
This study is to examine if hydrogen-rich saline reduced amyloid beta (Abeta) induced neural inflammation, and learning and memory deficits in a rat model. S-D male rats (n=84, 280-330g) were divided into three groups, sham-operated, Abeta1-42 injected and Abeta1-42 plus hydrogen-rich saline-treated animals. Hydrogen-rich saline (5ml/kg, i.p., daily) was injected for 14days after intracerebroventricular injection of Abeta1-42.
The levels of MDA, IL-6 and TNF-alpha were assessed by biochemical and ELISA analysis. Morris Water Maze and open field task were used to assess the memory dysfunction and motor dysfunction, respectively. LTP were used to detect the electrophysiology changes, HNE and GFAP immunohistochemistry were used to assess the oxidative stress and glial cell activation.
After Abeta1-42 injection, the levels of MDA, IL-6, and TNF-alpha were increased in brain tissues and hydrogen-rich saline treatment suppressed MDA, IL-6, and TNF-alpha concentration. Hydrogen-rich saline treatment improved Morris Water Maze and enhanced LTP in hippocampus blocked by Abeta1-42. Furthermore, hydrogen-rich saline treatment also decreased the immunoreactivitiy of HNE and GFAP in hippocampus induced by Abeta1-42. In conclusion, hydrogen-rich saline prevented Abeta-induced neuroinflammation and oxidative stress, which may contribute to the improvement of memory dysfunction in this rat model
References–https://www.ncbi.nlm.nih.gov/pubmed/20171955
Hydrogen-rich water attenuates brain damage and inflammation after traumatic brain injury in rats
ABSTRACT
Inflammation and oxidative stress are the two major causes of apoptosis after traumatic brain injury (TBI). Most previous studies of the neuroprotective effects of hydrogen-rich water on TBI primarily focused on antioxidant effects. The present study investigated whether hydrogen-rich water (HRW) could attenuate brain damage and inflammation after traumatic brain injury in rats. A TBI model was induced using a controlled cortical impact injury. HRW or distilled water was injected intraperitoneally daily following surgery. We measured survival rate, brain edema, blood-brain barrier (BBB) breakdown and neurological dysfunction in all animals. Changes in inflammatory cytokines, inflammatory cells and Cho/Cr metabolites in brain tissues were also detected. Our results demonstrated that TBI-challenged rats exhibited significant brain injuries that were characterized by decreased survival rate and increased BBB permeability, brain edema, and neurological dysfunction, while HRW treatment ameliorated the consequences of TBI. HRW treatment also decreased the levels of pro-inflammatory cytokines (TNF-α, IL-1β and HMGB1), inflammatory cell number (Iba1) and inflammatory metabolites (Cho) and increased the levels of an anti-inflammatory cytokine (IL-10) in the brain tissues of TBI-challenged rats. In conclusion, HRW could exert a neuroprotective effect against TBI and attenuate inflammation, which suggests HRW as an effective therapeutic strategy for TBI patients.
References–https://www.ncbi.nlm.nih.gov/pubmed/26826009
Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals
ABSTRACT
Acute oxidative stress induced by ischemia-reperfusion or inflammation causes serious damage to tissues, and persistent oxidative stress is accepted as one of the causes of many common diseases including cancer. We show here that hydrogen (H(2)) has potential as an antioxidant in preventive and therapeutic applications. We induced acute oxidative stress in cultured cells by three independent methods. H(2) selectively reduced the hydroxyl radical, the most cytotoxic of reactive oxygen species (ROS), and effectively protected cells; however, H(2) did not react with other ROS, which possess physiological roles. We used an acute rat model in which oxidative stress damage was induced in the brain by focal ischemia and reperfusion. The inhalation of H(2) gas markedly suppressed brain injury by buffering the effects of oxidative stress. Thus H(2) can be used as an effective antioxidant therapy; owing to its ability to rapidly diffuse across membranes, it can reach and react with cytotoxic ROS and thus protect against oxidative damage.
References–https://www.ncbi.nlm.nih.gov/pubmed/17486089
Hydrogen as a selective antioxidant: a review of clinical and experimental studies
ABSTRACT
Oxidative stress is implicated in the pathogenesis of many diseases; however, currently used antioxidants have a high toxicity that constrains administration to a narrow window of therapeutic dosage. There is a clear need for more effective and safer antioxidants. Diatomic hydrogen (H(2)) was proposed as a novel antioxidant that selectively reduces levels of toxic reactive-oxygen species. Recently, many studies have reported that H(2) (inhaled or orally ingested, typically as approximately 0.8 mM H(2)-saturated water), can exert beneficial effects in diverse animal models of ischaemia-reperfusion injury, and inflammatory and neurological disease. In the clinic, oral administration of H(2)-saturated water is reported to improve lipid and glucose metabolism in subjects with diabetes or impaired glucose tolerance; promising results have also been obtained in reducing inflammation in haemodialysis patients and treating metabolic syndrome. These studies suggest H(2) has selective antioxidant properties, and can exert antiapoptotic, antiinflammatory and antiallergy effects. This review summarizes recent research findings and mechanisms concerning the therapeutic potential of H(2).
References–https://www.ncbi.nlm.nih.gov/pubmed/21226992
Recent Progress Toward Hydrogen Medicine: Potential of Molecular Hydrogen for Preventive and Therapeutic Applications
ABSTRACT
Persistent oxidative stress is one of the major causes of most lifestyle-related diseases, cancer and the aging process. Acute oxidative stress directly causes serious damage to tissues. Despite the clinical importance of oxidative damage, antioxidants have been of limited therapeutic success. We have proposed that molecular hydrogen (H2) has potential as a “novel” antioxidant in preventive and therapeutic applications [Ohsawa et al., Nat Med. 2007: 13; 688-94]. H2 has a number of advantages as a potential antioxidant: H2 rapidly diffuses into tissues and cells, and it is mild enough neither to disturb metabolic redox reactions nor to affect reactive oxygen species (ROS) that function in cell signaling, thereby, there should be little adverse effects of consuming H2. There are several methods to ingest or consume H2, including inhaling hydrogen gas, drinking H2-dissolved water (hydrogen water), taking a hydrogen bath, injecting H2-dissolved saline (hydrogen saline), dropping hydrogen saline onto the eye, and increasing the production of intestinal H2 by bacteria. Since the publication of the first H2 paper in Nature Medicine in 2007, the biological effects of H2 have been confirmed by the publication of more than 38 diseases, physiological states and clinical tests in leading biological/medical journals, and several groups have started clinical examinations. Moreover, H2 shows not only effects against oxidative stress, but also various anti-inflammatory and anti-allergic effects. H2 regulates various gene expressions and protein-phosphorylations, though the molecular mechanisms underlying the marked effects of very small amounts of H2 remain elusive.
References–https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257754/
The evolution of molecular hydrogen: a noteworthy potential therapy with clinical significance
ABSTRACT
Studies on molecular hydrogen have evolved tremendously from its humble beginnings and have continued to change throughout the years. Hydrogen is extremely unique since it has the capability to act at the cellular level. Hydrogen is qualified to cross the blood brain barrier, to enter the mitochondria, and even has the ability to translocate to the nucleus under certain conditions.
Once in these ideal locations of the cell, previous studies have shown that hydrogen exerts antioxidant, anti-apoptotic, anti-inflammatory, and cytoprotective properties that are beneficial to the cell. Hydrogen is most commonly applied as a gas, water, saline, and can be applied in a variety of other mediums.
There are also few side effects involving hydrogen, thus making hydrogen a perfect medical gas candidate for the convention of novel therapeutic strategies against cardiovascular, cerebrovascular, cancer, metabolic, and respiratory diseases and disorders. Although hydrogen appears to be faultless at times, there still are several deficiencies or snares that need to be investigated by future studies. This review article seeks to delve and comprehensively analyze the research and experiments that alludes to molecular hydrogen being a novel therapeutic treatment that medicine desperately needs.
References–https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660246/
The Role of Inflammation in the Pathology of Acne
Oxidative stress in acne vulgaris: an important therapeutic targetAddressing Free Radical Oxidationin Acne Vulgari
Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injuryHydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injuryHydrogen-rich water protects against acetaminophen-induced hepatotoxicity in miceHydrogen-rich water protects against acetaminophen-induced hepatotoxicity in miceHydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injuryHydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injuryHydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injuryInjuryHydrogen–water enhances5-fluorouracil-induced inhibition ofcolon cancerHydrogen–water enhances5-fluorouracil-induced inhibition ofcolon cancerHydrogen–water enhances5-fluorouracil-induced inhibition ofcolon cancerTop of Form
ABSTRACT
The conventional perspective of acne pathogenesis holds that Propionibacterium acnes colonizes the duct of the sebaceous follicle, causing an innate immune response and the progression from a so-called noninflammatory comedo to an inflammatory papule, pustule, or nodule.
However, this viewpoint has come under increasing scrutiny over the last decade, as evidence has emerged supporting a role for inflammation at all stages of acne lesion development, perhaps subclinically even before comedo formation. The immunochemical pathways underlying the initiation and propagation of the inflammation in acne are complex and still being elucidated, but may involve Propionibacterium acnes as well as several inflammatory mediators and their target receptors, including cytokines, defensins, peptidases, sebum lipids, and neuropeptides.
This review presents evidence to support the notion that acne is primarily an inflammatory disease, challenging the current nomenclature of noninflammatory versus inflammatory acne lesions and suggesting that the nomenclature is outdated and incorrect. The evidence in support of acne as an inflammatory disease also has clinical implications, in that anti-inflammatory drugs used to treat the disease can be expected to exert effects against all lesion stages, albeit via distinct mechanisms of anti-inflammation.
References-https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3780801/
Oxidative stress in acne vulgaris: an important therapeutic target Addressing Free Radical Oxidation in Acne Vulgari
Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in mice Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in mice Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury
Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord Injury Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancer Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancer Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancer Top of Form
Oxidative stress in acne vulgaris: an important therapeutic target
ABSTRACT
Objective: There has been an increasing focus on the extent to which oxidative stress is involved in the pathophysiology of acne. The aim of this study is to investigate the existence of oxidative stress and inflammatory marker IL-8 in patients with acne vulgaris, and the role of oxidative stress as a therapeutic target in the treatment of acne vulgaris.
Methods:
A randomized prospective clinical trial was carried out on 56 patients of both sexes with age range of 14-35 years who attend to outpatient clinic in Al-Hussein Teaching Hospital-Kerbalaa -Iraq over a period from December 2011 to May 2012, all patients examined clinically by dermatologist and classified according to disease severity. Serum levels of glutathione (GSH), malondialdehyde (MDA) and interleukine -8 (IL-8) in the acne patients were measured by using ready- for- use Elisa kits, and compared to that of 28 healthy volunteers. Results: The results of the serum level analysis of MDA for the acne patients (expressed as the mean± standard deviation) was highly significant (P value ≤ 0.001) higher than that of healthy volunteers, while serum level of GSH was highly significant (P value ≤ 0.001) lower in acne patients compared to healthy volunteers; there is a significant difference (P value ≤ 0.05) found in serum levels of IL-8 between the acne patients and the healthy volunteers.
Conclusions: The results obtained in this study clearly showed the existence of oxidative stress in patients with acne vulgaris, and that oxidative stress along with inflammation play a critical role in acne pathogenesis; furthermore, oxidative stress in acne patients may represents a potential therapeutic target and interference with antioxidant is a rationale choice.
References-https://www.ejmanager.com/mnstemps/66/66-1345206572.pdf
Oxidants and anti-oxidants status in acne vulgaris patients with varying severity
Addressing Free Radical Oxidationin Acne Vulgari
Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in mice Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in miceHydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen–water enhances5-fluorouracil-induced inhibition of colon cancer Hydrogen–water enhances5-fluorouracil-induced inhibition ofcolon cancerHydrogen–water enhances5-fluorouracil-induced inhibition ofcolon cancerTop of Form
ABSTRACT
Acne vulgaris is a common dermatological disorder with a multifactorial pathogenesis. Oxidative status has been implicated in the pathogenesis of several skin diseases, including acne. This study was aimed to investigate the levels of oxidative stress biomarkers in acne vulgaris patients with varying severities. The study involved 156 patients with acne and 46 healthy human controls.
Based on clinical examination, patients were grouped into 3 subgroups as follows: mild, moderate, and severe acne. Oxidative stress was examined by measuring plasma levels of catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (TAC), and malondialdehyde (MDA). Plasma levels of MDA in acne patients were significantly higher as compared with that of the controls, whereas activities of the antioxidant enzymes SOD and CAT were lower. Moreover, TAC was also low in acne patients as compared with that of the controls. Higher MDA levels in the severe acne subgroup as compared with that of the mild and moderate subgroups were also observed. Furthermore, in the severe acne subgroup, a significant negative correlation was observed between MDA and CAT levels. The data suggests that oxidative stress plays a key role in acne progress and may be employed as a biomarker index to assess the disease’s activity and to monitor its treatment.
References-https://www.ncbi.nlm.nih.gov/pubmed/24795060
Addressing Free Radical Oxidation in Acne Vulgari
Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in mice Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in mice Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancer Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancer Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancerTop of Form
Addressing Free Radical Oxidation in Acne Vulgaris
ABSTRACT
Objective: Comparatively little attention has been paid to the role of free radical oxidation in acne vulgaris. Here, using the traditional abnormalities cited for acne, the authors address the role of free radical oxidation throughout the pathogenesis by detailing the chemistry that may contribute to clinical changes. To probe the effects of free radical oxidation and test an antioxidant, they conducted a preliminary study of topically applied vitamin E.
Methods: Seventeen patients with mild-to-moderate acne vulgaris were evaluated over an eight-week period in two private dermatology practices in this open-label study. All patients enrolled were on the same baseline regimen of salicylic acid and benzoyl peroxide. This regimen was then supplemented with topical vitamin E in sunflower seed oil.
Results:
At the end of the eight-week period, all patients demonstrated clinical improvement, as indicated by a reduction in the number of lesions and global mean difference. A statistically significant reduction was noted as early as Week 2. Enrolled patients also expressed a positive experience due to good tolerability and easy application.
Conclusion:
Although the exact pathogenesis of acne vulgaris remains unknown, the presence of excessive reactive oxygen species can be implicated in each of the major abnormalities involved. This presence, along with the positive results of the authors’ preliminary study,
demonstrates the need for more exploration on the use of topical antioxidants in limiting free radical oxidation in the acne model. This paper is designed to stimulate academic discussion regarding a new way of thinking about the disease state of acne.
References-https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756869/pdf/jcad_9_1_25.pdf
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The Role of Inflammation in the Pathology of Acne
Oxidative stress in acne vulgaris: an important therapeutic targetAddressing Free Radical Oxidationin Acne Vulgari
Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injuryHydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injuryHydrogen-rich water protects against acetaminophen-induced hepatotoxicity in miceHydrogen-rich water protects against acetaminophen-induced hepatotoxicity in miceHydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injuryHydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injuryHydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injuryInjuryHydrogen–water enhances5-fluorouracil-induced inhibition ofcolon cancerHydrogen–water enhances5-fluorouracil-induced inhibition ofcolon cancerHydrogen–water enhances5-fluorouracil-induced inhibition ofcolon cancerTop of Form
ABSTRACT
The conventional perspective of acne pathogenesis holds that Propionibacterium acnes colonizes the duct of the sebaceous follicle, causing an innate immune response and the progression from a so-called noninflammatory comedo to an inflammatory papule, pustule, or nodule.
However, this viewpoint has come under increasing scrutiny over the last decade, as evidence has emerged supporting a role for inflammation at all stages of acne lesion development, perhaps subclinically even before comedo formation. The immunochemical pathways underlying the initiation and propagation of the inflammation in acne are complex and still being elucidated, but may involve Propionibacterium acnes as well as several inflammatory mediators and their target receptors, including cytokines, defensins, peptidases, sebum lipids, and neuropeptides.
This review presents evidence to support the notion that acne is primarily an inflammatory disease, challenging the current nomenclature of noninflammatory versus inflammatory acne lesions and suggesting that the nomenclature is outdated and incorrect. The evidence in support of acne as an inflammatory disease also has clinical implications, in that anti-inflammatory drugs used to treat the disease can be expected to exert effects against all lesion stages, albeit via distinct mechanisms of anti-inflammation.
References-https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3780801/
Oxidative stress in acne vulgaris: an important therapeutic target Addressing Free Radical Oxidation in Acne Vulgari
Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in mice Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in mice Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury
Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord Injury Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancer Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancer Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancer Top of Form
Oxidative stress in acne vulgaris: an important therapeutic target
ABSTRACT
Objective: There has been an increasing focus on the extent to which oxidative stress is involved in the pathophysiology of acne. The aim of this study is to investigate the existence of oxidative stress and inflammatory marker IL-8 in patients with acne vulgaris, and the role of oxidative stress as a therapeutic target in the treatment of acne vulgaris.
Methods:
A randomized prospective clinical trial was carried out on 56 patients of both sexes with age range of 14-35 years who attend to outpatient clinic in Al-Hussein Teaching Hospital-Kerbalaa -Iraq over a period from December 2011 to May 2012, all patients examined clinically by dermatologist and classified according to disease severity. Serum levels of glutathione (GSH), malondialdehyde (MDA) and interleukine -8 (IL-8) in the acne patients were measured by using ready- for- use Elisa kits, and compared to that of 28 healthy volunteers. Results: The results of the serum level analysis of MDA for the acne patients (expressed as the mean± standard deviation) was highly significant (P value ≤ 0.001) higher than that of healthy volunteers, while serum level of GSH was highly significant (P value ≤ 0.001) lower in acne patients compared to healthy volunteers; there is a significant difference (P value ≤ 0.05) found in serum levels of IL-8 between the acne patients and the healthy volunteers.
Conclusions: The results obtained in this study clearly showed the existence of oxidative stress in patients with acne vulgaris, and that oxidative stress along with inflammation play a critical role in acne pathogenesis; furthermore, oxidative stress in acne patients may represents a potential therapeutic target and interference with antioxidant is a rationale choice.
References-https://www.ejmanager.com/mnstemps/66/66-1345206572.pdf
Oxidants and anti-oxidants status in acne vulgaris patients with varying severity
Addressing Free Radical Oxidationin Acne Vulgari
Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in mice Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in miceHydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen–water enhances5-fluorouracil-induced inhibition of colon cancer Hydrogen–water enhances5-fluorouracil-induced inhibition ofcolon cancerHydrogen–water enhances5-fluorouracil-induced inhibition ofcolon cancerTop of Form
ABSTRACT
Acne vulgaris is a common dermatological disorder with a multifactorial pathogenesis. Oxidative status has been implicated in the pathogenesis of several skin diseases, including acne. This study was aimed to investigate the levels of oxidative stress biomarkers in acne vulgaris patients with varying severities. The study involved 156 patients with acne and 46 healthy human controls.
Based on clinical examination, patients were grouped into 3 subgroups as follows: mild, moderate, and severe acne. Oxidative stress was examined by measuring plasma levels of catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (TAC), and malondialdehyde (MDA). Plasma levels of MDA in acne patients were significantly higher as compared with that of the controls, whereas activities of the antioxidant enzymes SOD and CAT were lower. Moreover, TAC was also low in acne patients as compared with that of the controls. Higher MDA levels in the severe acne subgroup as compared with that of the mild and moderate subgroups were also observed. Furthermore, in the severe acne subgroup, a significant negative correlation was observed between MDA and CAT levels. The data suggests that oxidative stress plays a key role in acne progress and may be employed as a biomarker index to assess the disease’s activity and to monitor its treatment.
References-https://www.ncbi.nlm.nih.gov/pubmed/24795060
Addressing Free Radical Oxidation in Acne Vulgari
Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in mice Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in mice Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancer Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancer Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancerTop of Form
Addressing Free Radical Oxidation in Acne Vulgaris
ABSTRACT
Objective: Comparatively little attention has been paid to the role of free radical oxidation in acne vulgaris. Here, using the traditional abnormalities cited for acne, the authors address the role of free radical oxidation throughout the pathogenesis by detailing the chemistry that may contribute to clinical changes. To probe the effects of free radical oxidation and test an antioxidant, they conducted a preliminary study of topically applied vitamin E.
Methods: Seventeen patients with mild-to-moderate acne vulgaris were evaluated over an eight-week period in two private dermatology practices in this open-label study. All patients enrolled were on the same baseline regimen of salicylic acid and benzoyl peroxide. This regimen was then supplemented with topical vitamin E in sunflower seed oil.
Results:
At the end of the eight-week period, all patients demonstrated clinical improvement, as indicated by a reduction in the number of lesions and global mean difference. A statistically significant reduction was noted as early as Week 2. Enrolled patients also expressed a positive experience due to good tolerability and easy application.
Conclusion:
Although the exact pathogenesis of acne vulgaris remains unknown, the presence of excessive reactive oxygen species can be implicated in each of the major abnormalities involved. This presence, along with the positive results of the authors’ preliminary study,
demonstrates the need for more exploration on the use of topical antioxidants in limiting free radical oxidation in the acne model. This paper is designed to stimulate academic discussion regarding a new way of thinking about the disease state of acne.
References-https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756869/pdf/jcad_9_1_25.pdf
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The Role of Inflammation in the Pathology of Acne
Oxidative stress in acne vulgaris: an important therapeutic targetAddressing Free Radical Oxidationin Acne Vulgari
Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injuryHydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injuryHydrogen-rich water protects against acetaminophen-induced hepatotoxicity in miceHydrogen-rich water protects against acetaminophen-induced hepatotoxicity in miceHydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injuryHydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injuryHydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injuryInjuryHydrogen–water enhances5-fluorouracil-induced inhibition ofcolon cancerHydrogen–water enhances5-fluorouracil-induced inhibition ofcolon cancerHydrogen–water enhances5-fluorouracil-induced inhibition ofcolon cancerTop of Form
ABSTRACT
The conventional perspective of acne pathogenesis holds that Propionibacterium acnes colonizes the duct of the sebaceous follicle, causing an innate immune response and the progression from a so-called noninflammatory comedo to an inflammatory papule, pustule, or nodule.
However, this viewpoint has come under increasing scrutiny over the last decade, as evidence has emerged supporting a role for inflammation at all stages of acne lesion development, perhaps subclinically even before comedo formation. The immunochemical pathways underlying the initiation and propagation of the inflammation in acne are complex and still being elucidated, but may involve Propionibacterium acnes as well as several inflammatory mediators and their target receptors, including cytokines, defensins, peptidases, sebum lipids, and neuropeptides.
This review presents evidence to support the notion that acne is primarily an inflammatory disease, challenging the current nomenclature of noninflammatory versus inflammatory acne lesions and suggesting that the nomenclature is outdated and incorrect. The evidence in support of acne as an inflammatory disease also has clinical implications, in that anti-inflammatory drugs used to treat the disease can be expected to exert effects against all lesion stages, albeit via distinct mechanisms of anti-inflammation.
References-https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3780801/
Oxidative stress in acne vulgaris: an important therapeutic target Addressing Free Radical Oxidation in Acne Vulgari
Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in mice Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in mice Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury
Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord Injury Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancer Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancer Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancer Top of Form
Oxidative stress in acne vulgaris: an important therapeutic target
ABSTRACT
Objective: There has been an increasing focus on the extent to which oxidative stress is involved in the pathophysiology of acne. The aim of this study is to investigate the existence of oxidative stress and inflammatory marker IL-8 in patients with acne vulgaris, and the role of oxidative stress as a therapeutic target in the treatment of acne vulgaris.
Methods:
A randomized prospective clinical trial was carried out on 56 patients of both sexes with age range of 14-35 years who attend to outpatient clinic in Al-Hussein Teaching Hospital-Kerbalaa -Iraq over a period from December 2011 to May 2012, all patients examined clinically by dermatologist and classified according to disease severity. Serum levels of glutathione (GSH), malondialdehyde (MDA) and interleukine -8 (IL-8) in the acne patients were measured by using ready- for- use Elisa kits, and compared to that of 28 healthy volunteers. Results: The results of the serum level analysis of MDA for the acne patients (expressed as the mean± standard deviation) was highly significant (P value ≤ 0.001) higher than that of healthy volunteers, while serum level of GSH was highly significant (P value ≤ 0.001) lower in acne patients compared to healthy volunteers; there is a significant difference (P value ≤ 0.05) found in serum levels of IL-8 between the acne patients and the healthy volunteers.
Conclusions: The results obtained in this study clearly showed the existence of oxidative stress in patients with acne vulgaris, and that oxidative stress along with inflammation play a critical role in acne pathogenesis; furthermore, oxidative stress in acne patients may represents a potential therapeutic target and interference with antioxidant is a rationale choice.
References-https://www.ejmanager.com/mnstemps/66/66-1345206572.pdf
Oxidants and anti-oxidants status in acne vulgaris patients with varying severity
Addressing Free Radical Oxidationin Acne Vulgari
Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in mice Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in miceHydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury Hydrogen–water enhances5-fluorouracil-induced inhibition of colon cancer Hydrogen–water enhances5-fluorouracil-induced inhibition ofcolon cancerHydrogen–water enhances5-fluorouracil-induced inhibition ofcolon cancerTop of Form
ABSTRACT
Acne vulgaris is a common dermatological disorder with a multifactorial pathogenesis. Oxidative status has been implicated in the pathogenesis of several skin diseases, including acne. This study was aimed to investigate the levels of oxidative stress biomarkers in acne vulgaris patients with varying severities. The study involved 156 patients with acne and 46 healthy human controls.
Based on clinical examination, patients were grouped into 3 subgroups as follows: mild, moderate, and severe acne. Oxidative stress was examined by measuring plasma levels of catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (TAC), and malondialdehyde (MDA). Plasma levels of MDA in acne patients were significantly higher as compared with that of the controls, whereas activities of the antioxidant enzymes SOD and CAT were lower. Moreover, TAC was also low in acne patients as compared with that of the controls. Higher MDA levels in the severe acne subgroup as compared with that of the mild and moderate subgroups were also observed. Furthermore, in the severe acne subgroup, a significant negative correlation was observed between MDA and CAT levels. The data suggests that oxidative stress plays a key role in acne progress and may be employed as a biomarker index to assess the disease’s activity and to monitor its treatment.
References-https://www.ncbi.nlm.nih.gov/pubmed/24795060
Abstract
It has been shown that molecular hydrogen acts as a therapeutic and preventive antioxidant by selectively reducing the hydroxyl radical, the most cytotoxic of the reactive oxygen species. In the present study, we tested the hypothesis that acoustic damage in guinea pigs can be attenuated by the consumption of molecular hydrogen. Guinea pigs received normal water or hydrogen-rich water for 14 days before they were exposed to 115 dB SPL 4-kHz octave band noise for 3h. Animals in each group underwent measurements for auditory brainstem response (ABR) or distortion-product otoacoustic emissions (DPOAEs) before the treatment (baseline) and immediately, 1, 3, 7, and 14 days after noise exposure. The ABR thresholds at 2 and 4 kHz were significantly better on post-noise days 1, 3, and 14 in hydrogen-treated animals when compared to the normal water-treated controls. Compared to the controls, the hydrogen-treated animals showed greater amplitude of DPOAE input/output growth functions during the recovery process, with statistical significance detected on post-noise days 3 and 7. These findings suggest that hydrogen can facilitate the recovery of hair cell function and attenuate noise-induced temporary hearing loss.
Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
References-https://pubmed.ncbi.nlm.nih.gov/20888392/
Abstract
Purpose: Retinal ischemia-reperfusion (I/R) injury by transient elevation of intraocular pressure (IOP) is known to induce neuronal damage through the generation of reactive oxygen species. Study results have indicated that molecular hydrogen (H(2)) is an efficient antioxidant gas that selectively reduces the hydroxyl radical (*OH) and suppresses oxidative stress-induced injury in several organs. This study was conducted to explore the neuroprotective effect of H(2)-loaded eye drops on retinal I/R injury.
Methods: Retinal ischemia was induced in rats by raising IOP for 60 minutes. H(2)-loaded eye drops were prepared by dissolving H(2) gas into a saline to saturated level and administered to the ocular surface continuously during the ischemia and/or reperfusion periods. One day after I/R injury, apoptotic cells in the retina were quantified, and oxidative stress was evaluated by markers such as 4-hydroxynonenal and 8-hydroxy-2-deoxyguanosine. Seven days after I/R injury, retinal damage was quantified by measuring the thickness of the retina.
Results: When H(2)-loaded eye drops were continuously administered, H(2) concentration in the vitreous body immediately increased and I/R-induced *OH level decreased. The drops reduced the number of retinal apoptotic and oxidative stress marker-positive cells and prevented retinal thinning with an accompanying activation of Müller glia, astrocytes, and microglia. The drops improved the recovery of retinal thickness by >70%.
Conclusions: H(2) has no known toxic effects on the human body. Thus, the results suggest that H(2)-loaded eye drops are a highly useful neuroprotective and antioxidative therapeutic treatment for acute retinal I/R injury.
References-https://pubmed.ncbi.nlm.nih.gov/19834032/
Abstract
Aim: Auditory neuropathy (AN) is a hearing disorder characterized by abnormal auditory nerve function with preservation of normal cochlear hair cells. This study was designed to investigate whether treatment with molecular hydrogen (H(2)), which can remedy damage in various organs via reducing oxidative stress, inflammation and apoptosis, is beneficial to ouabain-induced AN in gerbils.
Methods: AN model was made by local application of ouabain (1 mmol/L, 20 mL) to the round window membrane in male Mongolian gerbils. H(2) treatment was given twice by exposing the animals to H(2) (1%, 2%, and 4%) for 60 min at 1 h and 6 h after ouabain application. Before and 7 d after ouabain application, the hearing status of the animals was evaluated using the auditory brainstem response (ABR) approach, the hear cell function was evaluated with distortion product otoacoustic emissions (DPOAE). Seven days after ouabain application, the changes in the cochleae, especially the spiral ganglion neurons (SGNs), were morphologically studied. TUNEL staining and immunofluorescent staining for activated caspase-3 were used to assess the apoptosis of SGNs.
Results: Treatment with H(2) (2% and 4%) markedly attenuated the click and tone burst-evoked ABR threshold shift at 4, 8, and 16 kHz in ouabain-exposed animals. Neither local ouabain application, nor H(2) treatment changed the amplitude of DPOAE at 4, 8, and 16 kHz. Morphological study showed that treatment with H(2) (2%) significantly alleviated SGN damage and attenuated the loss of SGN density for each turn of cochlea in ouabain-exposed animals. Furthermore, ouabain caused significantly higher numbers of apoptotic SGNs in the cochlea, which was significantly attenuated by the H(2) treatment. However, ouabain did not change the morphology of cochlear hair cells.
Conclusion: The results demonstrate that H(2) treatment is beneficial to ouabain-induced AN via reducing apoptosis. Thus, H(2) might be a potential agent for treating hearing impairment in AN patients.
References-https://pubmed.ncbi.nlm.nih.gov/22388074/
Abstract
Objective: Cisplatin, an anticancer drug used extensively to treat a broad range of tumors, has strong ototoxic side effects induced by reactive oxygen species (ROS). Recently, it has been reported that hydrogen gas (H(2)) is a new antioxidant by selectively reducing hydroxyl radical, the most cytotoxic ROS. The present study was designed to investigate whether H(2) treatment is beneficial to cisplatin-induced ototoxicity via reducing oxidative stress.
Methods: The animals were intraperitoneally given a 30 min infusion of 16 mg/kg cisplatin or the same volume of saline. H(2) treatment was given twice with 2% H(2) inhalation for 60 min starting at 1h and 6h after cisplatin or saline injection, respectively. The hearing status of all animals was evaluated by auditory brainstem responses (ABR). The hair cell damage was observed by phalloidin staining. In addition, the levels of oxidative products in serum and cochlear tissue were measured.
Results: We found that H(2) treatment significantly attenuated cisplatin-induced hearing loss evaluated by click-evoked and tone burst ABR threshold. Furthermore, histological analysis revealed that 2% H(2) treatment significantly alleviated cisplatin-induced hair cell damage in the organ of corti. In addition, cisplatin significantly increased the levels of malondialdehyde (MDA) and 8-iso-prostaglandin F2α (8-iso-PGF2α) in serum and cochlear tissue, which was attenuated by H(2) treatment.
Conclusion: These results demonstrate that H(2) is beneficial to cisplatin-induced ototoxicity via reducing oxidative stress. Therefore, H(2) has potential for improving the quality of life of patients during chemotherapy by efficiently mitigating the cisplatin ototoxicity.
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
References-https://pubmed.ncbi.nlm.nih.gov/22055279/
Abstract
Objective: To investigate the effect of molecular hydrogen (H2) in a rat model subjected to optic nerve crush (ONC).
Methods: We tested the hypothesis that after optic nerve crush (ONC), retinal ganglion cell (RGC) could be protected by H₂. Rats in different groups received saline or hydrogen-rich saline every day for 14 days after ONC. Retinas from animals in each group underwent measurements of hematoxylin and eosin (H&E) staining, cholera toxin beta (CTB) tracing, gamma synuclein staining, and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) staining 2 weeks post operation. Flash visual evoked potentials (FVEP) and pupillary light reflex (PLR) were then tested to evaluate the function of optic nerve. The malondialdehyde (MDA) level in retina was evaluated.
Results: H&E, gamma synuclein staining and CTB tracing showed that the survival rate of RGCs in hydrogen saline-treated group was significantly higher than that in saline-treated group. Apoptosis of RGCs assessed by TUNEL staining were less observed in hydrogen saline-treated group. The MDA level in retina of H₂ group was much lower than that in placebo group. Furthermore, animals treated with hydrogen saline showed better function of optic nerve in assessments of FVEP and PLR.
Conclusion: These results demonstrated that H₂ protects RGCs and helps preserve the visual function after ONC and had a neuroprotective effect in a rat model subjected to ONC.
References-https://pubmed.ncbi.nlm.nih.gov/24915536/
Abstract
Oxidative reactions are thought to be a major cause of light-induced retinal degeneration. This study was designed to investigate the effects of hydrogen-rich saline (HRS) on the prevention and treatment of light-induced retinal injury in rats. Male Sprague-Dawley rats were divided randomly into three groups: light damage, HRS prevention (5 ml/kg, 30 min before intensive light exposure), and HRS treatment (5 ml/kg per day for 5 days, after intensive light exposure), respectively. The right eye of each rat was exposed to 5000 lux constant white light-emitting diode (LED) light for 3 h, and the left eye was covered to serve as the blank control. Electroretinograms were recorded 5 days later, and the thickness of the outer nuclear layer (ONL) was measured after hematoxylin and eosin (H&E) staining. The results showed that the electroretinogram b-wave amplitudes and the mean ONL thicknesses of rats were significantly greater in the HRS prevention (P < 0.001) and treatment (P < 0.001) groups than in the light damage. These results indicated that peritoneal injection of HRS provides protection and treatment against light-induced retinal degeneration in rats.
References-https://pubmed.ncbi.nlm.nih.gov/24004679/
Abstract
The purpose of the current study was to evaluate hydrogen-saturated saline protecting intensive narrow band noise-induced hearing loss. Guinea pigs were divided into three groups: hydrogen-saturated saline; normal saline; and control. For saline administration, the guinea pigs were given daily abdominal injections (1 ml/100 g) 3 days before and 1 h before narrow band noise exposure (2.5-3.5 kHz 130 dB SPL, 1 h). The guinea pigs in the control group received no treatment. The hearing function was assessed by the auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) recording. The changes of free radicals in the cochlea before noise exposure, and immediately and 7 days after noise exposure were also examined. By Scanning electron microscopy and succinate dehydrogenase staining, we found that pre-treatment with hydrogen-saturated saline significantly reduced noise-induced hair cell damage and hearing loss. We also found that the malondialdehyde, lipid peroxidation, and hydroxyl levels were significantly lower in the hydrogen-saturated saline group after noise trauma, indicating that hydrogen-saturated saline can decrease the amount of harmful free radicals caused by noise trauma. Our findings suggest that hydrogen-saturated saline is effective in preventing intensive narrow band noise-induced hearing loss through the antioxidant effect.
Reference-https://pubmed.ncbi.nlm.nih.gov/24945316/
AIM
To explore the effect of saturated hydrogen saline on blue light-induced retinal damage in rats.
METHODS
The retinal damage of rats was induced by blue light exposure for 6 hours and examined 8 hours, 16 hours and 24 hours after the exposure. One hundred female Sprague-Dawley rats were randomly divided into four groups. Group 1 included 30 rats received light exposure without any other treatment. Group 2 included 30 rats received light exposure with intraperitoneal injection of normal saline. Group 3 included 30 rats received light exposure with intraperitoneal injection of saturated hydrogen saline. And Group 4 included the other 10 rats which did not receive any treatment. The amount of intraperitoneal injection of saturated hydrogen saline and normal saline was calculated in the ratio of 1ml/100g of rat weight. Specimens were collected and processed by H-E staining, ultrastructure observation, biochemical measurement. Morphological changes were observed by light microscope and transmission electron microscope (TEM) and the retinal outer nuclear layer (ONL) thickness was measured by IPP 6.0, while the malondialdehyde (MDA) was measured by colorimetric determination at 532 nm.
RESULTS
Although the structure of retina in Group 1 and Group 2 was injured heavily, the injury in Group 3 was mild. The differences between Group 1 and Group 2 were not significant. Compared with the rats in Group 1 and Group 2, the ones in Group 3 had more clearly demarcated retina structure and more ordered cells by light microscope and TEM observation. The ONL thicknesses (400 times) of four groups at each time point except between Group 1 and Group 2 were significantly different (P<0.05). The thicknesses of the ONL in Group 1 at three time points were 30.41±4.04µm, 26.11±2.82µm and 20.63±1.06µm, in Group 2 were 31.62±4.54µm, 25.08±3.63µm and 19.07±3.86µm, in Group 3 were 29.75±3.62µm, 28.83±1.97µm and 27.61±1.83µm. In Group 4 the mean of the thickness was 37.35±1.37µm. As time went by, the damage grew more severely. At 24h point, the differences were most significant. Compared with Group 4, the thickness was 46.23% thinner in Group 1, 50.29% thinner in Group 2 and 28.04% thinner in Group 3. The stack structures of membranous disc in Group 3 were injured slightly, but in Group 1 and Group 2 the damage was more obvious by TEM. Compared with Group 4 at each time point, the content of MDA in Group 1 was higher (P<0.05). The content of MDA in Group 3 was significantly lower than those of Group 1 (P<0.05) and Group 2 (P<0.05). Between the Group 1 and Group 2, the MDA concentration at each time point was no significant difference (P>0.05).
CONCLUSION
Saturated hydrogen saline could protect the retina from light-induced damage by attenuating oxidative stress.
Keywords: retina, hydrogen, antioxidants, phototoxicity
Reference-https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3359028/
Hydrogen mediates suppression of colon inflammation induced by dextran sodium sulfate
ABSTRACT
Abstract
Objective: Retinal neovascularization or retinopathy is a proliferative disorder of the retinal capillaries and is the primary cause of blindness. Some studies have shown that oxidative stress plays an important role in hyperoxia-induced retinal neovascularization. Previous reports have indicated that hydrogen has a therapeutic, antioxidant activity by selectively reducing hydroxyl radicals. This study examined the therapeutic effect of hydrogen saline on retinopathy in an established mouse model of hyperoxia-induced retinopathy.
Methods: Mouse pups were exposed to 75% O(2) from postnatal day 7 (P7) to P12. Hydrogen saline was administered by intraperitoneal injection (5 ml/kg) daily for 5 days. On P17, the pups were decapitated, and retinal neovascularization was assessed using fluorescence imaging and histopathological examination. Vascular endothelial growth factor (VEGF) expression was evaluated using real-time polymerase chain reaction and fluorescence immunohistochemistry. Oxidative stress was quantified based on the malondialdehyde (MDA) level.
Results: Hydrogen saline decreased retinal neovascularization, reduced the mRNA and protein expression of VEGF, and suppressed the MDA levels.
Conclusions: Hydrogen saline may be a potential treatment for hyperoxia-induced retinopathy that acts via the inhibition of oxidative stress and the reduction of VEGF expression.
Reference-https://pubmed.ncbi.nlm.nih.gov/22156508/
The Effects of Hydrogen-Rich Saline on the Contractile and Structural Changes of Intestine Induced by Ischemia-Reperfusion in Rats
ABSTRACT
Psoriasis and parapsoriasis en plaques are chronic inflammatory skin diseases, both representing therapeutic challenge in daily practice and adversely affecting the quality of life. Reactive oxygen species (ROS) has been evidenced to be involved in the pathogenesis of the chronic inflammatory diseases. We now report that hydrogen water, an effective ROS scavenger, has significant and rapid improvement in disease severity and quality of life for patients with psoriasis and parapsoriasis en plaques. At week 8, our parallel-controlled trial revealed 24.4% of patients (10/41) receiving hydrogen-water bathing achieved at least 75% improvement in Psoriasis Area Severity Index (PASI) score compared with 2.9% of patients (1/34) of the control group (Pc = 0.022, OR = 0.094, 95%CI = [0.011, 0.777]). Of patients, 56.1% (23/41) who received bathing achieved at least 50% improvement in PASI score compared with only 17.7%(6/34) of the control group (P = 0.001, OR = 0.168, 95%CI = [0.057, 0.492]). The significant improvement of pruritus was also observed (P = 3.94 × 10−4). Besides, complete response was observed in 33.3% of patients (2/6) of parapsoriasis en plaques and partial response in 66.7% (4/6) at week 8. Our findings suggested that hydrogen-water bathing therapy could fulfill the unmet need for these chronic inflammatory skin diseases.
Reference-https://www.nature.com/articles/s41598-018-26388-3#:~:text=Reactive%20oxygen%20species%20(ROS)%20has,psoriasis%20and%20parapsoriasis%20en%20plaques.
Hydrogen-rich saline protects against intestinal ischemia/reperfusion injury in rats
ABSTRACT
Psoriasis, a chronic inflammatory skin disease, is caused by infiltrating lymphocytes and associated cytokines, including tumor necrosis factor (TNF)α, interleukin (IL)-6, and IL-17. Effective treatments, including pathogenesis-based biological agents against psoriasis, are currently under development. Although the role of reactive oxygen species (ROS) in the pathogenesis of psoriasis has been investigated, it remains to be fully elucidated; ROS-targeted therapeutic strategies are also lacking at present. Therefore, the objective of the present study was to assess whether H2, a ROS scavenger, has a therapeutic effect on psoriasis-associated inflammation by reducing hydroxyl radicals or peroxynitrite in the immunogenic psoriasis cascade. Three methods were used to administer H2: Drop infusion of saline containing 1 ppm H2 (H2-saline), inhalation of 3% H2 gas, and drinking of water containing a high concentration (5-7-ppm) of H2 (high-H2 water). Treatment efficacy was estimated using the disease activity score 28 (DAS28) system, based on C-reactive protein levels, and the psoriasis area and severity index (PASI) score, determined at baseline and following each H2 treatment. Furthermore, levels of TNFα, IL-6, and IL-17 were analyzed. The DAS28 and PASI score of the three patients decreased during H2 treatment, regardless of the administration method. The psoriatic skin lesions almost disappeared at the end of the treatment. IL-6 levels decreased during H2 treatment in Case 1 and 2. IL-17, whose concentration was high in Case 1, was reduced following H2 treatment, and TNFα also decreased in Case 1. In conclusion, H2 administration reduced inflammation associated with psoriasis in the three cases examined and it may therefore be considered as a treatment strategy for psoriasis-associated skin lesions and arthritis.
Reference-https://pubmed.ncbi.nlm.nih.gov/25936373/
Hydrogen mediates suppression of colon inflammation induced by dextran sodium sulfate
ABSTRACT
Background: Tumour necrosis factor alpha (TNFalpha) blockade using infliximab, a chimeric anti-TNFalpha antibody, is an effective treatment for both psoriasis and psoriatic arthritis (PsA).
Objective: To analyse the early effects of infliximab treatment on serial skin and synovial tissue biopsy samples.
Methods: Twelve patients with both active psoriasis and PsA received a single infusion of either infliximab (3 mg/kg) (n = 6) or placebo (n = 6) intravenously. Synovial tissue and lesional skin biopsy specimens were obtained at baseline and 48 hours after treatment. Immunohistochemical analysis was performed to analyse the inflammatory infiltrate. In situ detection of apoptotic cells was performed by TUNEL assay and by immunohistochemical staining with anti-caspase-3 antibodies. Stained tissue sections were evaluated by digital image analysis.
Results: A significant reduction in mean (SEM) T cell numbers was found in both lesional epidermis (baseline 37 (11) cells/mm, 48 hours 26 (11), p = 0.028) and synovial tissue (67 (56) cells/mm(2)v 32 (30), p = 0.043) after infliximab treatment, but not after placebo treatment (epidermis 18 (8) v 43 (20), NS; synovium 110 (62) v 46 (21), NS). Similarly, the number of macrophages in the synovial sublining was significantly reduced after anti-TNFalpha treatment (100 (73) v 10 (8), p = 0.043). The changes in cell numbers could not be explained by induction of apoptosis at the site of inflammation.
Conclusions: The effects of anti-TNFalpha therapy in psoriasis and psoriatic arthritis may be explained by decreased cell infiltration in lesional skin and inflamed synovial tissue early after initiation of treatment.
Reference-https://pubmed.ncbi.nlm.nih.gov/15194570/
Consumption of water containing a high concentration of molecular hydrogen reduces oxidative stress and disease activity in patients with rheumatoid arthritis: an open-label pilot study
ABSTRACT
Background
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by the destruction of bone and cartilage. Although its etiology is unknown, the hydroxyl radical has been suggested to be involved in the pathogenesis of RA. Recently, molecular hydrogen (H2) was demonstrated to be a selective scavenger for the hydroxyl radical. Also, the method to prepare water containing extremely high concentration of H2 has been developed. We hypothesized that H2 in the water could complement conventional therapy by reducing the oxidative stress in RA.
Methods
Twenty patients with rheumatoid arthritis (RA) drank 530 ml of water containing 4 to 5 ppm molecular hydrogen (high H2 water) every day for 4 weeks. After a 4-week wash-out period, the patients drank the high H2 water for another 4 weeks. Urinary 8-hydroxydeoxyguanine (8-OHdG) and disease activity (DAS28, using C-reactive protein [CRP] levels) was estimated at the end of each 4-week period.
Results
Drinking high H2 water seems to raise the concentration of H2 more than the H2 saturated (1.6 ppm) water in vivo. Urinary 8-OHdG was significantly reduced by 14.3% (p < 0.01) on average. DAS28 also decreased from 3.83 to 3.02 (p < 0.01) during the same period. After the wash-out period, both the urinary 8-OHdG and the mean DAS28 decreased, compared to the end of the drinking period. During the second drinking period, the mean DAS28 was reduced from 2.83 to 2.26 (p < 0.01). Urinary 8-OHdG was not further reduced but remained below the baseline value. All the 5 patients with early RA (duration < 12 months) who did not show antibodies against cyclic citrullinated peptides (ACPAs) achieved remission, and 4 of them became symptom-free at the end of the study.
Conclusions
The results suggest that the hydroxyl radical scavenger H2 effectively reduces oxidative stress in patients with this condition. The symptoms of RA were significantly improved with high H2 water.
Keywords: Arthritis, Rheumatoid; Oxidative stress; Reactive oxygen species; Molecular hydrogen; 8-hydroxylguanine; Hydroxyl radical: DNA repair; Error protein
Reference-https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563451/#idm140029240584160title
Molecular hydrogen decelerates rheumatoid arthritis progression through inhibition of oxidative stress
ABSTRACT
Rheumatoid arthritis (RA) is a chronic inflammatory disease which results in progressive destruction of the joint. In this study, we examined if the hydrogen could inhibit inflammation in a mouse model of collagen-induced arthritis (CIA) via oxidative stress on RA-FLSs. Moreover, to identify the mechanisms of action, we evaluated the effect of hydrogen on RA-FLSs development and the expression of pro-inflammatory cytokines and signaling pathways. Based on our result, H2 enriched medium can increase super oxide dismutase (SOD) level following H2O2 treatment and decrease 8-hydroxy-2’-deoxyguanosine (8-OHdG) level. Since H2O2 treatment activates MAPK, NF-κB and TGF-β1 in cells, our study suggested that H2 could inhibit H2O2 activated MAPK and NF-κB activation as well as TGF-β1 expression in treated cells. Taken together, our data suggested that H2 can directly neutralize OH and ONOO- to reduce oxidative stress. Moreover, MAPK and NF-κB pathway also play roles in oxidative damage caused by H2O2 in RA-FLSs. H2 can provide protection to cells against inflammation, which may be related to inhibition of the activation of MAPK and NF-κB.
Keywords: Rheumatoid arthritis, hydrogen, SOD, NF-κB, TGF-β1
Reference-https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095341/
Hydrogen mediates suppression of colon inflammation induced by dextran sodium sulfate
ABSTRACT
The aim of this study was to demonstrate the safety and efficacy of H2-saline infusion for treatment of rheumatoid arthritis (RA). We conducted a randomized, double-blind, placebo-controlled investigation of the infusion of 1 ppm H2-dissolved saline (H2-saline) in 24 RA patients. Patients were randomized 1:1 to receive 500 ml of either H2-saline or placebo-saline, which was drop infused intravenously (DIV) daily for 5 days. The disease activity score in 28 joints (DAS28) was measured at baseline, immediately post infusion, and after 4 weeks. Therapeutic effects of H2-saline on joint inflammation were estimated by measuring serum biomarkers for RA, tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), and urinary 8-hydroxydeoxyguanosine (8-OHdG). In the H2-infused group, average DAS28 decreased from 5.18 ± 1.16 to 4.02 ± 1.25 immediately post infusion and reached 3.74 ± 1.22 after 4 weeks. No significant decrease in DAS28 was observed in the placebo group throughout the study. IL-6 levels in the H2 group significantly decreased in 4 weeks by 37.3 ± 62.0% compared to baseline, whereas it increased by 33.6 ± 34.4% in the placebo group. TNFα levels did not change remarkably in the H2 or placebo groups in 4 weeks post-infusion compared to baseline. The relative ratio of 8-OHdG in the H2 group also significantly decreased by 4.7%. After 4 weeks, MMP3 was significantly reduced by 19.2% ± 24.6% in the H2 group, and increased by 16.9% ± 50.2% in the placebo group. Drop infusion of H2 safely and effectively reduced RA disease activity.
Reference-https://www.sciencedirect.com/science/article/pii/S1567576914002124
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