Introduction
Molecular hydrogen research before 2007
Molecular hydrogen research in and after year 2007
Pathophysiology | No. of articles | % |
---|---|---|
Oxidative stress | 224 | 69.8 |
(I/R injury | 80 | 24.9) |
(Others | 144 | 44.9) |
Inflammation | 66 | 20.6 |
Metabolism | 20 | 6.2 |
Others | 11 | 3.4 |
Diseases and conditions | References |
---|---|
Brain | |
Cerebrovascular diseases (CVD)
| |
Cerebral I/R injury | |
Hypertensive stroke | [110] |
Brain injury secondary to intracerebral hemorrhage | [28] |
Subarachnoid hemorrhage | |
Brain injury other than CVD
| |
Traumatic brain injury | |
Deep hypothermic circulatory arrest-induced brain damage | [57] |
Neurodegenerative diseases
| |
Parkinson’s disease | |
Alzheimer’s disease | |
Others
| |
Restraint-induced dementia | [121] |
Senile dementia in senescence-accelerated mice | [122] |
LPS-induced neuroinflammation | |
Oxidative stress-induced neuronal cell damage | |
Spinal Cord and peripheral nerve | |
Spinal cord I/R injury | |
Spinal cord injury | |
Neuropathic pain | |
Hyperalgesia | |
Eye | |
Retinal I/R injury | |
Diabetic retinopathy | |
Hyperoxia-induced retinopathy | [137] |
Light-induced retinopathy | |
Glutamine-induced retinopathy | [50] |
S-nitroso-N-acetylpenicillamine-induced retinopathy | [140] |
Optic nerve crush | [141] |
Selenite-induced cataract | [142] |
Corneal alkali-burn | [55] |
Anti-inflammatory effects on LPS-activated retinal microglia cells | [64] |
Ear | |
Hearing loss | |
Cisplatin-induced ototoxicity | |
Ouabain-induced ototoxicity | [151] |
Oral Cavity | |
Periodontitis | [32] |
Periodontal oxidative damage | [152] |
Lung | |
Lung I/R injury | |
Oxygen-induced lung injury | |
Ventilation-induced lung injury | |
LPS-induced acute lung injury | |
Intestinal I/R-induced lung injury | [159] |
Burn-induced lung injury | [160] |
Paraquat-induced lung injury | |
igarette smoking lung injury | [163] |
Smoke inhalation lung injury | [74] |
Pulmonary hypertension | |
Heart | |
Myocardial infarction and I/R injury | |
Diabetic cardiomyopathy | [40] |
Sleep apnea-induced left ventricular remodeling | |
Ventricular hypertrophy | [167] |
Stomach | |
Stress-induced gastric ulceration | [38] |
Aspirin-induced gastric ulceration | |
Intestine | |
Intestinal I/R injury | |
Ulcerative colitis | |
Colon inflammation | [174] |
Sepsis-induced intestinal injury | [87] |
Necrotizing enterocolitis | [175] |
Liver | |
Liver I/R injury | |
Chronic hepatitis B | [179] |
Nonalcoholic steatohepatitis | [180] |
Liver injury induced by massive hepatectomy | |
Liver injury induced by obstructive jaundice | [31] |
Liver injury induced by endotoxin | [35] |
Liver injury induced by acetaminophen | [47] |
Liver injury induced by carbon tetrachloride | [42] |
Liver injury induced by concanavalin A | [182] |
Liver cirrhosis | [183] |
Liver fibrosis | [184] |
Pancreas | |
Acute pancreatitis | |
Peritoneum | |
Acute peritonitis | [68] |
Kidney | |
Renal I/R injury | |
Acute renal injury | |
Hypertensive renal injury | [69] |
Cisplatin-induced nephropathy | |
Gentamicin-induced nephrotoxicity | [198] |
Inhibition of AGEs production | [199] |
Renal calcium deposition | [200] |
Bladder | |
Interstitial cystitis | [201] |
Reproductive organ | |
Testicular I/R injury | |
Erectile dysfunction | [204] |
Nicotine-induced testicular oxidative stress | [205] |
Cigarette smoke-induced testicular damage | [206] |
Skin | |
I/R injury | |
UV-induced skin injury | |
Acute erythematous skin disease | [212] |
Atopic dermatitis | |
Psoriasis | [215] |
Pressure ulcer | [216] |
Burn | |
Arsenic toxicity | [217] |
Bone and Joint | |
Rheumatoid arthritis | |
Osteoporosis | |
Bone loss induced by microgravity | [34] |
TNFα-induced osteoblast injury | [220] |
NO-induced cartilage toxicity | [221] |
Skeletal Muscle and soft tissue | |
I/R injury in skeletal muscle | [222] |
Inflammatory and mitochondrial myopathies | [223] |
Muscle fatigue | [224] |
Sports-related soft tissue injury | [225] |
Blood vessel | |
Atherosclerosis | |
AGEs-induced blood vessel damage | [228] |
Neointimal hyperplasia | [29] |
Hyperplasia in arterialized vein graft | [229] |
Vascular dysfunction | [60] |
Vascular endothelial function | [230] |
Blood and Bone Marrow | |
Aplastic anemia | [231] |
Maintenance of multipotential stroma/mesenchymal stem cells | [232] |
Neutrophil function | [233] |
Inhibition of collagen-induced platelet aggregation | [234] |
Improvement of blood fluidity | [235] |
Metabolism | |
Diabetes mellitus | |
Hyperlipidemia | |
Metabolic syndrome | |
Metabolic process-related gene expression | [248] |
Oxidized low density lipoprotein-induced cell toxicity | [54] |
Serum alkalinization | [249] |
Exercise-induced metabolic acidosis | [250] |
Inflammation/Allergy | |
Sepsis | |
LPS/IFNγ-induced NO production | [27] |
LPS-induced inflammatory response | [90] |
LPS-induced vascular permeability | |
Zymosan-induced inflammation | [257] |
Carrageenan-induced paw edema | [258] |
Inflammatory response of cardiopulmonary bypass | [259] |
Type I allergy | [26] |
Asthma | [63] |
Perinatal Disorders | |
Neonatal cerebral hypoxia | |
LPS-induced fetal lung injury | [15] |
Preeclampsia | |
Cancer | |
Growth of tongue carcinoma cells | [266] |
Fe-NTA-induced nephrotoxicity and tumor progression | [65] |
Radiation-induced thymic lymphoma | [267] |
Tumor angiogenesis | [268] |
Enhancement of 5-FU antitumor efficacy | [269] |
Radiation | |
Cardiac damage | [270] |
Lung damage | [271] |
Testicular damage | [272] |
Skin damage | |
Germ, hematopoietic and other cell damage | |
Radiation-induced adverse effects | [281] |
Radiation-induced immune dysfunction | [282] |
Intoxication | |
Carbon monoxide | |
Sevoflurane | |
Doxorubicin-induced heart failure | [289] |
Melamine-induced urinary stone | [290] |
Chlorpyrifos-induced neurotoxicity | [291] |
Transplantation | |
Heart | |
Lung | |
Kidney | |
Intestine | |
Pancreas | [302] |
Osteochondral grafts | [303] |
Acute GVHD | |
Resuscitation | |
Cardiac arrest | |
Hemorrhagic shock | |
Dialysis | |
Hemodialysis | |
Peritoneal dialysis | |
Others | |
Lifespan extension | [316] |
Sperm motility | [317] |
Decompression sickness | [318] |
Genotoxicity and mutagenicity | [319] |
Plant | |
Root organogenesis | |
Salt tolerance | |
Postharvest ripening | [323] |
Stomatal closure | [324] |
Radish sprout tolerance to UVA | [325] |
High light stress | [326] |
Phytohormone signaling and stress responses | [327] |
Tolerance to paraquat-induced oxidative stress | [328] |
Cadmium toxicity | |
Mercury toxicity | [331] |
Molecular mechanisms of the effects of hydrogen
Biological effects and in vivo kinetics of hydrogen | References |
---|---|
Superoxide formation in brain slices in mice | [332] |
Gene expression profiles and signal transduction pathways evaluated by DNA microarray and RNA-seq in rodents | |
Comparison of intermittent and continuous administration of hydrogen gas in rats | [11]a
|
Safety of hydrogen inhalation in patients with cerebral ischemia | [333] |
A convenient method to estimate the concentration of hydrogen in water | [334] |
Hydrogen consumption in human body after hydrogen administration | |
Ghrelin induction and secretion by hydrogen-dissolved water in mice | [95]a
|
Additive effects of hydrogen and NO | |
In vivo kinetics of hydrogen after hydrogen administration in rodents | |
Lack of reactivity of hydrogen with peroxynitrite | [338] |
Antioxidant activity of nano-bubble hydrogen-dissolved water | [339] |
Additive effects of hydrogen gas and hydrogen-rich water | [12] |
Clinical studies of molecular hydrogen
Authors/Year | Disease | Sample size | Open-label (OL), double-blind (DB), or single-blind (SB) | Hydrogen administration | Summary of the outcome |
---|---|---|---|---|---|
Kajiyama et al. [236]/2008 | Diabetes mellitus type II | 30 | DB | Water | Improvement of fractions of low-density lipoprotein (LDL)-cholesterol and a glucose tolerance test. |
Nakao et al. [245]/2010 | Metabolic syndrome | 20 | OL | Water | Improvement of urinary markers for oxidative stress such as SOD and TBARS, and increase of high-density lipoprotein (HDL)-cholesterol. |
Nakayama et al. [311]/2010 | Chronic renal failure | 29 | OL | Dialysis | Amelioration of hypertension and improvement of markers for oxidative stress and inflammation. |
Ito et al. [223]/2011 | Inflammatory and mitochondrial myopathies | 31 | OL/DB | Water | OL: Improvement of the serum lactate/pyruvate ratio in mitochondrial myopathies and the serum matrix metalloproteinse-3 level in polymyositis/dermatomyositis. |
DB: Improvement of the serum lactate. | |||||
Kang et al. [281]/2011 | Radiation-induced adverse effects for liver tumors | 49 | OL | Water | Improvement of quality of life (QOL) scores during radiotherapy. |
Reduction of blood reactive oxygen metabolites and maintenance of blood oxidation potential. | |||||
Ishibashi et al. [218]/2012 | Rheumatoid arthritis | 20 | OL | Water | Improvement of disease activity score for rheumatoid arthritis (DAS28). |
Decrease of urinary 8-OHdG. | |||||
Aoki et al. [224]/2012 | Muscle fatigue | 10 | DB | Water | Improvement of muscle fatigue in young athletes |
Li et al. [216]/2013 | Pressure skin ulcer | 22 | OL | Water | Wound size reduction and early recovery from skin pressure ulcer. |
Matsumoto et al. [201]/2013 | Interstitial cystitis | 30 | DB | Water | No significant effect on symptoms. |
Reduction of the bladder pain score in 11 % of patients. | |||||
Nagatani et al. [106]/2013 | Cerebral ischemia | 38 | OL | Intravenous infusion | Confirmation of safety of intravenous H2 infusion. |
Decrease of MDA-LDL, a serum marker for oxidative stress, in a subset of patients. | |||||
Shin et al. [45]/2013 | UV-induced skin injury | 28 | OL | Gas | Prevention and modulation of UV-induced skin inflammation, intrinsic skin aging, and photo aging process through reduction of MMP-1, IL-6, and IL-1b mRNA expression. |
Song et al. [243]/2013 | Hyperlipidemia | 20 | OL | Water | Decrease of total serum cholesterol, LDL-cholesterol, apolipoprotein (apo) B100, and apoE |
Xia et al. [179]/2013 | Chronic hepatitis B | 60 | DB | Water | Attenuation of oxidative stress |
Yoritaka et al. [96]/2013 | Parkinson disease | 17 | DB | Water | Improvement of Total Unified Parkinson’s Disease Rating Scale (UPDRS) and exacerbation after termination of H2 water. |
Ishibashi et al. [219]/2014 | Rheumatoid arthritis | 24 | DB | Intravenous saline infusion | Improvement of DAS28. |
Decrease of serum IL-6, MMP3, CRP, and urinary 8-OHdG. | |||||
Ostojic et al. [225]/2014 | Sports-related soft tissue injury | 36 | SB | H2-rich tablets and topical H2 packs | Decrease of plasma viscosity. |
Faster recovery from soft tissue injury. | |||||
Ostojic et al. [250]/2014 | Exercise-induced metabolic acidosis | 52 | DB | Water | Increased blood alkalinity in physically active men. |
Sakai et al. [230]/2014 | Vascular endothelial function. | 34 | DB | Water | Increased flow-mediated dilation of branchial artery, suggesting that H2 can serve as a modulator of vasomotor function of vasculature. |
Song et al. [244]/2015 | Hyperlipidemia | 68 | DB | Water | Down-regulation of plasma levels of total cholesterol, and LDL-cholesterol, followed by increased plasma pre-β -HDL, apoM, and decreased plasma oxidized-LDL, apoB100. |
Date | Disease | Affiliation | Status |
---|---|---|---|
7/16/2008 | Interstitial cystitis | Koshinkai Hosp. | Finished[201] |
8/21/2008 | Impaired glucose tolerance and impaired fasting glycaemia | Digestive tract internal medicine, Kyoto Prefectural University of Medicine | Finished [236]. |
7/17/2009 | Mild cognitive impairment | Neuropsychiatry, Tsukuba Univ. | Finished |
1/11/2011 | Chronic hemodialysis | Nephrology, Fukushima Medical University | Trial in progress |
6/2/2011 | Acute cerebral infarction | Neurosurgery, Self Defense Medical College | Calling for participants[106] |
9/30/2011 | Normal adults | Faculty of Health Sciences, Kyorin Univ. | Finished |
12/4/2011 | Acute myocardial infarction | Cardiology, Keio Univ. | Calling for participants |
3/14/2012 | Parkinson’s disease | Neurology, Juntendo Univ. | Finished [96] |
10/16/2012 | Multiple system atrophy, Progressive supranuclear palsy | Neurology, Juntendo Univ. | Trial in progress |
2/13/2013 | Parkinson’s disease | Neurology, Juntendo Univ. | Calling for participants |
5/1/2013 | Chronic obstructive pulmonary disease | Respiratory Medicine, Juntendo Univ. | Trial in progress |
5/20/2013 | Hepatitis and liver cirrhosis | Gastroenterology and Hepatology, Okayama Univ. | In preparation |
11/22/2013 | Post cardiac arrest syndrome | Emergency and Critical care medicine, Keio Univ. | Calling for participants |
2/22/2014 | Eye disease | Ophthalmology, Nippon Medical school | Finished |
7/1/2014 | Acute myocardial infarction | Cardiology, National Center for Global Health and Medicine | Calling for participants |
7/29/2014 | Subarachnoid hemorrhage | Neurosurgery, Self Defense Medical College | Calling for participants [113] |
8/1/2014 | Lung transplantation | General thoracic surgery, Osaka Univ. | Calling for participants |
10/27/2014 | Retinal artery occlusion | Ophthalmology, Nippon Medical school | Calling for participants |
7/3/2015 | Type 2 diabetes mellitus | Tokyo Metropolitan Institute of Gerontology | Calling for participants |