Molecular hydrogen as a preventive and therapeutic medical gas: Initiation, development and potential of hydrogen medicine

Pharmacology and Therapeutics

Volumn 144, Issue 1, 2014, Pages 1-11

  Ohta, Shigeo ^a  

^a Graduate School of Medicine   (Japan)

Author keywords

Anti inflammation; Antioxidant; Clinical examination; No adverse effect; Oxidative stress; Reactive oxygen species

Indexed keywords

HYDROGEN; HYDROXYL RADICAL; INERT GAS; OXIDIZING AGENT; REACTIVE OXYGEN METABOLITE; ANTIINFLAMMATORY AGENT; GAS;

ANTIINFLAMMATORY ACTIVITY; APOPTOSIS; CELL METABOLISM; DRUG EFFICACY; DRUG MECHANISM; DRUG SAFETY; ENERGY METABOLISM; GENE EXPRESSION REGULATION; HUMAN; NONHUMAN; OXIDATION REDUCTION REACTION; OXIDATIVE STRESS; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; ADMINISTRATION AND DOSAGE; ANIMAL; DRUG EFFECTS; GAS; METABOLISM;

ANIMALS; ANTI-INFLAMMATORY AGENTS; APOPTOSIS; ENERGY METABOLISM; GASES; GENE EXPRESSION REGULATION; HUMANS; HYDROGEN; OXIDATION-REDUCTION; OXIDATIVE STRESS; REACTIVE OXYGEN SPECIES;

EID: 84906934199     PISSN: 01637258     EISSN: 1879016X     Source Type: Journal    
DOI: 10.1016/j.pharmthera.2014.04.006     Document Type: Review

References (144)

1. J.H. Abraini, M.C. Gardette-Chauffour, E. Martinez, J.C. Rostain, and C. Lemaire Psychophysiological reactions in humans during an open sea dive to 500 m with a hydrogen-helium-oxygen mixture J Appl Physiol 76 1994 1113 1118
2. D.N. Abrous, M. Koehl, and M. Le Moal Adult neurogenesis: from precursors to network and physiology Physiol Rev 85 2005 523 569
3. R. Agarwal Smoking, oxidative stress and inflammation: impact on resting energy expenditure in diabetic nephropathy BMC Nephrol 6 2005 13
4. J.K. Andersen Oxidative stress in neurodegeneration: cause or consequence? Nat Med 10 2004 S18 S25 (Suppl.)
5. K. Aoki, A. Nakao, T. Adachi, Y. Matsui, and S. Miyakawa Pilot study: Effects of drinking hydrogen-rich water on muscle fatigue caused by acute exercise in elite athletes Med Gas Res 2 2012 12
6. P.K. Bagul, and S.K. Banerjee Insulin resistance, oxidative stress and cardiovascular complications: role of sirtuins Curr Pharm Des 19 2013 5663 5677
7. N. Bashan, J. Kovsan, I. Kachko, H. Ovadia, and A. Rudich Positive and negative regulation of insulin signaling by reactive oxygen and nitrogen species Physiol Rev 89 2009 27 71
8. S. Becker, and J.M. Wojtowicz A model of hippocampal neurogenesis in memory and mood disorders Trends Cogn Sci 11 2007 70 76
9. E.L. Bell, T.A. Klimova, J. Eisenbart, C.T. Moraes, M.P. Murphy, and G.R. Budinger et al. The Qo site of the mitochondrial complex III is required for the transduction of hypoxic signaling via reactive oxygen species production J Cell Biol 177 2007 1029 1036
10. E.L. Bell, T.A. Klimova, J. Eisenbart, P.T. Schumacker, and N.S. Chandel Mitochondrial reactive oxygen species trigger hypoxia-inducible factor-dependent extension of the replicative life span during hypoxia Mol Cell Biol 27 2007 5737 5745
11. G. Bjelakovic, D. Nikolova, L.L. Gluud, R.G. Simonetti, and C. Gluud Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis JAMA 297 2007 842 857
12. D. Brambilla, C. Mancuso, M.R. Scuderi, P. Bosco, G. Cantarella, and L. Lempereur et al. The role of antioxidant supplement in immune system, neoplastic, and neurodegenerative disorders: a point of view for an assessment of the risk/benefit profile Nutr J 7 2008 29
13. A.C. Brewer, S.B. Mustafi, T.V. Murray, N.S. Rajasekaran, and I.J. Benjamin Reductive stress linked to small HSPs, G6PD, and Nrf2 pathways in heart disease Antioxid Redox Signal 18 2013 1114 1127
14. B.M. Buchholz, D.J. Kaczorowski, R. Sugimoto, R. Yang, Y. Wang, and T.R. Billiar et al. Hydrogen inhalation ameliorates oxidative stress in transplantation induced intestinal graft injury Am J Transplant 8 2008 2015 2024
15. -) in aqueous solution J Phys Chem Ref Data 17 1988 513 886
16. J. Cai, Z. Kang, K. Liu, W. Liu, R. Li, and J.H. Zhang et al. Neuroprotective effects of hydrogen saline in neonatal hypoxia-ischemia rat model Brain Res 1256 2009 129 137
17. J. Cai, Z. Kang, W.W. Liu, X. Luo, S. Qiang, and J.H. Zhang et al. Hydrogen therapy reduces apoptosis in neonatal hypoxia-ischemia rat model Neurosci Lett 441 2008 167 172
18. W.W. Cai, M.H. Zhang, Y.S. Yu, and J.H. Cai Treatment with hydrogen molecule alleviates TNFalpha-induced cell injury in osteoblast Mol Cell Biochem 373 2013 1 9
19. J.S. Cardinal, J. Zhan, Y. Wang, R. Sugimoto, A. Tsung, and K.R. McCurry et al. Oral hydrogen water prevents chronic allograft nephropathy in rats Kidney Int 77 2010 101 109
20. N.S. Chandel, W.C. Trzyna, D.S. McClintock, and P.T. Schumacker Role of oxidants in NF-kappa B activation and TNF-alpha gene transcription induced by hypoxia and endotoxin J Immunol 165 2000 1013 1021
21. N.S. Chandel, M.G. Vander Heiden, C.B. Thompson, and P.T. Schumacker Redox regulation of p53 during hypoxia Oncogene 19 2000 3840 3848
22. C.H. Chen, A. Manaenko, Y. Zhan, W.W. Liu, R.P. Ostrowki, and J. Tang et al. Hydrogen gas reduced acute hyperglycemia-enhanced hemorrhagic transformation in a focal ischemia rat model Neuroscience 169 2010 402 414
23. H. Chen, Y.P. Sun, Y. Li, W.W. Liu, H.G. Xiang, and L.Y. Fan et al. Hydrogen-rich saline ameliorates the severity of l-arginine-induced acute pancreatitis in rats Biochem Biophys Res Commun 393 2010 308 313
24. H.G. Chen, K.L. Xie, H.Z. Han, W.N. Wang, D.Q. Liu, and G.L. Wang et al. Heme oxygenase-1 mediates the anti-inflammatory effect of molecular hydrogen in LPS-stimulated RAW 264.7 macrophages Int J Surg 11 2013 1060 1066
25. Y. Chuai, F. Gao, B. Li, L. Zhao, L. Qian, and F. Cao et al. Hydrogen-rich saline attenuates radiation-induced male germ cell loss in mice through reducing hydroxyl radicals Biochem J 442 2012 49 56
26. Y. Collins, E.T. Chouchani, A.M. James, K.E. Menger, H.M. Cocheme, and M.P. Murphy Mitochondrial redox signalling at a glance J Cell Sci 125 2012 801 806
27. S. Delaney, D.A. Jarem, C.B. Volle, and C.J. Yennie Chemical and biological consequences of oxidatively damaged guanine in DNA Free Radic Res 46 2012 420 441
28. W. Droge Free radicals in the physiological control of cell function Physiol Rev 82 2002 47 95
29. M. El Assar, J. Angulo, and L. Rodriguez-Manas Oxidative stress and vascular inflammation in aging Free Radic Biol Med 65 2013 380 401
30. J. Endo, M. Sano, T. Katayama, T. Hishiki, K. Shinmura, and S. Morizane et al. Metabolic remodeling induced by mitochondrial aldehyde stress stimulates tolerance to oxidative stress in the heart Circ Res 105 2009 1118 1127
31. A. Federico, E. Cardaioli, P. Da Pozzo, P. Formichi, G.N. Gallus, and E. Radi Mitochondria, oxidative stress and neurodegeneration J Neurol Sci 322 2012 254 262
32. R. Ferrari, C. Ceconi, S. Curello, A. Cargnoni, E. Pasini, and O. Visioli The occurrence of oxidative stress during reperfusion in experimental animals and men Cardiovasc Drugs Ther 5 Suppl. 2 1991 277 287
33. T. Finkel Oxygen radicals and signaling Curr Opin Cell Biol 10 1998 248 253
34. T. Finkel, and N.J. Holbrook Oxidants, oxidative stress and the biology of ageing Nature 408 2000 239 247
35. P. Fontanari, M. Badier, C. Guillot, C. Tomei, H. Burnet, and B. Gardette et al. Changes in maximal performance of inspiratory and skeletal muscles during and after the 7.1-MPa Hydra 10 record human dive Eur J Appl Physiol 81 2000 325 328
36. J. Fritsch, O. Lenz, and B. Friedrich Structure, function and biosynthesis of O(2)-tolerant hydrogenases Nat Rev Microbiol 11 2013 106 114
37. Y. Fu, M. Ito, Y. Fujita, M. Ichihara, A. Masuda, and Y. Suzuki et al. Molecular hydrogen is protective against 6-hydroxydopamine-induced nigrostriatal degeneration in a rat model of Parkinson's disease Neurosci Lett 453 2009 81 85
38. K. Fujita, T. Seike, N. Yutsudo, M. Ohno, H. Yamada, and H. Yamaguchi et al. Hydrogen in drinking water reduces dopaminergic neuronal loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease PLoS One 4 2009 e7247
39. L. Gan, and J.A. Johnson Oxidative damage and the Nrf2-ARE pathway in neurodegenerative diseases Biochim Biophys Acta 2013 (Epub ahead of print)
40. A.D. Garg, A.M. Dudek, G.B. Ferreira, T. Verfaillie, P. Vandenabeele, and D.V. Krysko et al. ROS-induced autophagy in cancer cells assists in evasion from determinants of immunogenic cell death Autophagy 9 2013 1292 1307
41. D. Grassi, G. Desideri, L. Ferri, A. Aggio, S. Tiberti, and C. Ferri Oxidative stress and endothelial dysfunction: say no to cigarette smoking! Curr Pharm Des 16 2010 2539 2550
42. D.G. Hackam Review: antioxidant supplements for primary and secondary prevention do not decrease mortality ACP J Club 147 2007 4
43. B. Halliwell, and J.M. Gutteridge Biologically relevant metal ion-dependent hydroxyl radical generation. An update FEBS Lett 307 1992 108 112
44. T. Hanaoka, N. Kamimura, T. Yokota, S. Takai, and S. Ohta Molecular hydrogen protects chondrocytes from oxidative stress and indirectly alters gene expressions through reducing peroxynitrite derived from nitric oxide Med Gas Res 1 2011 18
45. M.I. Harma, M. Harma, and O. Erel Measuring plasma oxidative stress biomarkers in sport medicine Eur J Appl Physiol 97 2006 505 (author reply 506-508)
46. K. Hayashida, M. Sano, N. Kamimura, T. Yokota, M. Suzuki, and Y. Maekawa et al. H(2) gas improves functional outcome after cardiac arrest to an extent comparable to therapeutic hypothermia in a rat model J Am Heart Assoc 1 2012 e003459
47. K. Hayashida, M. Sano, I. Ohsawa, K. Shinmura, K. Tamaki, and K. Kimura et al. Inhalation of hydrogen gas reduces infarct size in the rat model of myocardial ischemia-reperfusion injury Biochem Biophys Res Commun 373 2008 30 35
48. S. Hercberg, E. Kesse-Guyot, N. Druesne-Pecollo, M. Touvier, A. Favier, and P. Latino-Martel et al. Incidence of cancers, ischemic cardiovascular diseases and mortality during 5-year follow-up after stopping antioxidant vitamins and minerals supplements: a postintervention follow-up in the SU.VI.MAX Study Int J Cancer 127 2010 1875 1881
49. C.S. Huang, T. Kawamura, Y. Toyoda, and A. Nakao Recent advances in hydrogen research as a therapeutic medical gas Free Radic Res 44 2010 971 982
50. C.S. Huang, T. Kawamura, X. Peng, N. Tochigi, N. Shigemura, and T.R. Billiar et al. Hydrogen inhalation reduced epithelial apoptosis in ventilator-induced lung injury via a mechanism involving nuclear factor-kappa B activation Biochem Biophys Res Commun 408 2011 253 258
51. M. Hugyecz, E. Mracskó, P. Hertelendy, E. Farkas, F. Domoki, and F. Bari Hydrogen supplemented air inhalation reduces changes of prooxidant enzyme and gap junction protein levels after transient global cerebral ischemia in the rat hippocampus Brain Res 1404 2011 31 38
52. A. Iio, M. Ito, T. Itoh, R. Terazawa, Y. Fujita, and Y. Nozawa et al. Molecular hydrogen attenuates fatty acid uptake and lipid accumulation through downregulating CD36 expression in HepG2 cells Med Gas Res 3 2013 6
53. T. Ishibashi Molecular hydrogen: new antioxidant and anti-inflammatory therapy for rheumatoid arthritis and related diseases Curr Pharm Des 19 2013 6375 6381
54. T. Ishibashi, B. Sato, M. Rikitake, T. Seo, R. Kurokawa, and Y. Hara et al. 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 Med Gas Res 2 2012 27
55. M. Ito, T. Ibi, K. Sahashi, M. Ichihara, and K. Ohno Open-label trial and randomized, double-blind, placebo-controlled, crossover trial of hydrogen-enriched water for mitochondrial and inflammatory myopathies Med Gas Res 1 2011 24
56. T. Itoh, Y. Fujita, M. Ito, A. Masuda, K. Ohno, and M. Ichihara et al. Molecular hydrogen suppresses FcepsilonRI-mediated signal transduction and prevents degranulation of mast cells Biochem Biophys Res Commun 389 2009 651 656
57. A. Jazwa, and A. Cuadrado Targeting heme oxygenase-1 for neuroprotection and neuroinflammation in neurodegenerative diseases Curr Drug Targets 11 2010 1517 1531
58. M. Kajimura, R. Fukuda, R.M. Bateman, T. Yamamoto, and M. Suematsu Interactions of multiple gas-transducing systems: hallmarks and uncertainties of CO, NO, and H2S gas biology Antioxid Redox Signal 13 2010 157 192
59. M. Kajiya, K. Sato, M.J. Silva, K. Ouhara, P.M. Do, and K.T. Shanmugam et al. Hydrogen from intestinal bacteria is protective for Concanavalin A-induced hepatitis Biochem Biophys Res Commun 386 2009 316 321
60. M. Kajiya, M.J. Silva, K. Sato, K. Ouhara, and T. Kawai Hydrogen mediates suppression of colon inflammation induced by dextran sodium sulfate Biochem Biophys Res Commun 386 2009 11 15
61. S. Kajiyama, G. Hasegawa, M. Asano, H. Hosoda, M. Fukui, and N. Nakamura et al. Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance Nutr Res 28 2008 137 143
62. N. Kamimura, K. Nishimaki, I. Ohsawa, and S. Ohta Molecular Hydrogen Improves Obesity and Diabetes by Inducing Hepatic FGF21 and Stimulating Energy Metabolism in db/db Mice Obesity (Silver Spring) 19 2011 1396 1403
63. K.M. Kang, Y.N. Kang, I.B. Choi, Y. Gu, T. Kawamura, and Y. Toyoda et al. Effects of drinking hydrogen-rich water on the quality of life of patients treated with radiotherapy for liver tumors Med Gas Res 1 2011 11
64. K. Kashfi, and K.R. Olson Biology and therapeutic potential of hydrogen sulfide and hydrogen sulfide-releasing chimeras Biochem Pharmacol 85 2013 689 703
65. D. Kawai, A. Takaki, A. Nakatsuka, J. Wada, N. Tamaki, and T. Yasunaka et al. Hydrogen-rich water prevents progression of nonalcoholic steatohepatitis and accompanying hepatocarcinogenesis in mice Hepatology 56 2012 912 921
66. T. Kawamura, C.S. Huang, N. Tochigi, S. Lee, N. Shigemura, and T.R. Billiar et al. Inhaled hydrogen gas therapy for prevention of lung transplant-induced ischemia/reperfusion injury in rats Transplantation 90 2010 1344 1351
67. T. Kawamura, N. Wakabayashi, N. Shigemura, C.S. Huang, K. Masutani, and Y. Tanaka et al. Hydrogen gas reduces hyperoxic lung injury via the Nrf2 pathway in vivo Am J Physiol Lung Cell Mol Physiol 304 2013 L646 L656
68. H. Kawasaki, J. Guan, and K. Tamama Hydrogen gas treatment prolongs replicative lifespan of bone marrow multipotential stromal cells in vitro while preserving differentiation and paracrine potentials Biochem Biophys Res Commun 397 2010 608 613
69. Y.W. Kim, and T.V. Byzova Oxidative stress in angiogenesis and vascular disease Blood 123 2014 625 631
70. H. Kimura Hydrogen sulfide: from brain to gut Antioxid Redox Signal 12 2010 1111 1123
71. M. Kubota, S. Shimmura, S. Kubota, H. Miyashita, N. Kato, and K. Noda et al. Hydrogen and N-acetyl-L-cysteine rescue oxidative stress-induced angiogenesis in a mouse corneal alkali-burn model Invest Ophthalmol Vis Sci 52 2011 427 433
72. L. Li, G. Ishdorj, and S.B. Gibson Reactive oxygen species regulation of autophagy in cancer: implications for cancer treatment Free Radic Biol Med 53 2012 1399 1410
73. G.M. Li, M.H. Ji, X.J. Sun, Q.T. Zeng, M. Tian, and Y.X. Fan et al. Effects of hydrogen-rich saline treatment on polymicrobial sepsis J Surg Res 181 2013 279 286
74. D.Z. Li, Q.X. Zhang, X.X. Dong, H.D. Li, and X. Ma 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 J Bone Miner Metab 2013 (Epub ahead of print)
75. R.S. Lillo, and E.C. Parker Mixed-gas model for predicting decompression sickness in rats J Appl Physiol 89 2000 2107 2116
76. R.S. Lillo, E.C. Parker, and W.R. Porter Decompression comparison of helium and hydrogen in rats J Appl Physiol 82 1997 892 901
77. M.T. Lin, and M.F. Beal Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases Nature 443 2006 787 795
78. B. Lipinski Hydroxyl radical and its scavengers in health and disease Oxid Med Cell Longev 2011 2011 809696
79. H. Liu, R. Colavitti, I.I. Rovira, and T. Finkel Redox-dependent transcriptional regulation Circ Res 97 2005 967 974
80. J. Liu, X. Wang, M.K. Shigenaga, H.C. Yeo, A. Mori, and B.N. Ames Immobilization stress causes oxidative damage to lipid, protein, and DNA in the brain of rats FASEB J 10 1996 1532 1538
81. J.M. Mates, J.A. Segura, F.J. Alonso, and J. Marquez Oxidative stress in apoptosis and cancer: an update Arch Toxicol 86 2012 1649 1665
82. A. Matsumoto, M. Yamafuji, T. Tachibana, Y. Nakabeppu, M. Noda, and H. Nakaya Oral 'hydrogen water' induces neuroprotective ghrelin secretion in mice Sci Rep 3 2013 3273
83. R. Motterlini, and L.E. Otterbein The therapeutic potential of carbon monoxide Nat Rev Drug Discov 9 2010 728 743
84. K. Nagata, N. Nakashima-Kamimura, T. Mikami, I. Ohsawa, and S. Ohta Consumption of molecular hydrogen prevents the stress-induced impairments in hippocampus-dependent learning tasks during chronic physical restraint in mice Neuropsychopharmacology 34 2009 501 508
85. K. Nagatani, H. Nawashiro, S. Takeuchi, S. Tomura, N. Otani, and H. Osada et al. Safety of intravenous administration of hydrogen-enriched fluid in patients with acute cerebral ischemia: initial clinical studies Med Gas Res 3 2013 13
86. Y. Nakai, B. Sato, S. Ushiama, S. Okada, K. Abe, and S. Arai Hepatic oxidoreduction-related genes are upregulated by administration of hydrogen-saturated drinking water Biosci Biotechnol Biochem 75 2011 774 776
87. A. Nakao, D.J. Kaczorowski, Y. Wang, J.S. Cardinal, B.M. Buchholz, and R. Sugimoto et al. Amelioration of rat cardiac cold ischemia/reperfusion injury with inhaled hydrogen or carbon monoxide, or both J Heart Lung Transplant 29 2010 544 553
88. A. Nakao, Y. Toyoda, P. Sharma, M. Evans, and N. Guthrie Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome-an open label pilot study J Clin Biochem Nutr 46 2010 140 149
89. N. Nakashima-Kamimura, T. Mori, I. Ohsawa, S. Asoh, and S. Ohta Molecular hydrogen alleviates nephrotoxicity induced by an anti-cancer drug cisplatin without compromising anti-tumor activity in mice Cancer Chemother Pharmacol 64 2009 753 761
90. M. Nakayama, S. Kabayama, H. Nakano, W.J. Zhu, H. Terawaki, and K. Nakayama et al. Biological effects of electrolyzed water in hemodialysis Nephron Clin Pract 112 2009 c9 c15
91. M. Nakayama, H. Nakano, H. Hamada, N. Itami, R. Nakazawa, and S. Ito A novel bioactive haemodialysis system using dissolved dihydrogen (H2) produced by water electrolysis: a clinical trial Nephrol Dial Transplant 25 2010 3026 3033
92. E. Niki Lipid peroxidation: physiological levels and dual biological effects Free Radic Biol Med 47 2009 469 484
93. E. Niki Biomarkers of lipid peroxidation in clinical material Biochim Biophys Acta 1840 2014 809 817
94. Y. Ning, Y. Shang, H. Huang, J. Zhang, Y. Dong, and W. Xu et al. Attenuation of cigarette smoke-induced airway mucus production by hydrogen-rich saline in rats PLoS One 8 2013 e83429
95. K. Noda, N. Shigemura, Y. Tanaka, T. Kawamura, S. Hyun Lim, and K. Kokubo et al. A novel method of preserving cardiac grafts using a hydrogen-rich water bath J Heart Lung Transplant 32 2013 241 250
96. H. Oharazawa, T. Igarashi, T. Yokota, H. Fujii, H. Suzuki, and M. Machide et al. Protection of the retina by rapid diffusion of hydrogen: administration of hydrogen-loaded eye drops in retinal ischemia-reperfusion injury Invest Ophthalmol Vis Sci 51 2010 487 492
97. I. Ohsawa, M. Ishikawa, K. Takahashi, M. Watanabe, K. Nishimaki, and K. Yamagata et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals Nat Med 13 2007 688 694
98. I. Ohsawa, K. Nishimaki, K. Yamagata, M. Ishikawa, and S. Ohta Consumption of hydrogen water prevents atherosclerosis in apolipoprotein E knockout mice Biochem Biophys Res Commun 377 2008 1195 1198
99. S. Ohta Recent progress toward hydrogen medicine: potential of molecular hydrogen for preventive and therapeutic applications Curr Pharm Des 17 2011 2241 2252
100. S. Ohta Molecular hydrogen is a novel antioxidant to efficiently reduce oxidative stress with potential for the improvement of mitochondrial diseases Biochim Biophys Acta 1820 2012 586 594
101. H. Ono, Y. Nishijima, N. Adachi, M. Sakamoto, Y. Kudo, and K. Kaneko et al. A basic study on molecular hydrogen (H2) inhalation in acute cerebral ischemia patients for safety check with physiological parameters and measurement of blood H2 level Med Gas Res 2 2012 21
102. H. Ono, Y. Nishijima, N. Adachi, M. Sakamoto, Y. Kudo, and J. Nakazawa et al. 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 Med Gas Res 2 2012 14
103. H. Ono, Y. Nishijima, N. Adachi, S. Tachibana, S. Chitoku, and S. Mukaihara et al. Improved brain MRI indices in the acute brain stem infarct sites treated with hydroxyl radical scavengers, Edaravone and hydrogen, as compared to Edaravone alone. A non-controlled study Med Gas Res 1 2011 12
104. D.J. Park, A. Agarwal, and J.F. George Heme oxygenase-1 expression in murine dendritic cell subpopulations: effect on CD8 + dendritic cell differentiation in vivo Am J Pathol 176 2010 2831 2839
105. R. Radi Peroxynitrite, a stealthy biological oxidant J Biol Chem 288 2013 26464 26472
106. S. Reuter, S.C. Gupta, M.M. Chaturvedi, and B.B. Aggarwal Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med 49 2010 1603 1616
107. M. Ristow, and K. Zarse How increased oxidative stress promotes longevity and metabolic health: The concept of mitochondrial hormesis (mitohormesis) Exp Gerontol 45 2010 410 418
108. A. Sahay, and R. Hen Adult hippocampal neurogenesis in depression Nat Neurosci 10 2007 1110 1115
109. R.I. Salganik The benefits and hazards of antioxidants: controlling apoptosis and other protective mechanisms in cancer patients and the human population J Am Coll Nutr 20 2001 464S 472S (discussion 473S-475S)
110. H. Sauer, M. Wartenberg, and J. Hescheler Reactive oxygen species as intracellular messengers during cell growth and differentiation Cell Physiol Biochem 11 2001 173 186
111. A.H. Schapira Mitochondria in the aetiology and pathogenesis of Parkinson's disease Lancet Neurol 7 2008 97 109
112. M.P. Schoenfeld, R.R. Ansari, A. Nakao, and D. Wink A hypothesis on biological protection from space radiation through the use of new therapeutic gases as medical counter measures Med Gas Res 2 2012 8
113. M.P. Schoenfeld, R.R. Ansari, J.F. Zakrajsek, T.R. Billiar, Y. Toyoda, and D.A. Wink et al. Hydrogen therapy may reduce the risks related to radiation-induced oxidative stress in space flight Med Hypotheses 76 2011 117 118
114. K. Setsukinai, Y. Urano, K. Kakinuma, H.J. Majima, and T. Nagano Development of novel fluorescence probes that can reliably detect reactive oxygen species and distinguish specific species J Biol Chem 278 2003 3170 3175
115. A. Shimouchi, K. Nose, M. Shirai, and T. Kondo Estimation of molecular hydrogen consumption in the human whole body after the ingestion of hydrogen-rich water Adv Exp Med Biol 737 2012 245 250
116. T. Shinbo, K. Kokubo, Y. Sato, S. Hagiri, R. Hataishi, and M. Hirose et al. Breathing nitric oxide plus hydrogen gas reduces ischemia-reperfusion injury and nitrotyrosine production in murine heart Am J Physiol Heart Circ Physiol 305 2013 H542 H550
117. G. Song, M. Li, H. Sang, L. Zhang, X. Li, and S. Yao et al. Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome J Lipid Res 54 2013 1884 1893
118. S.R. Steinhubl Why have antioxidants failed in clinical trials? Am J Cardiol 101 2008 14D 19D
119. Q. Sun, J. Cai, S. Liu, Y. Liu, W. Xu, and H. Tao et al. Hydrogen-rich saline provides protection against hyperoxic lung injury J Surg Res 165 2011 e43 e49
120. Q. Sun, J. Cai, J. Zhou, H. Tao, J.H. Zhang, and W. Zhang et al. Hydrogen-rich saline reduces delayed neurologic sequelae in experimental carbon monoxide toxicity Crit Care Med 39 2011 765 769
121. Q. Sun, Z. Kang, J. Cai, W. Liu, Y. Liu, and J.H. Zhang et al. Hydrogen-rich saline protects myocardium against ischemia/reperfusion injury in rats Exp Biol Med (Maywood) 234 2009 1212 1219
122. C. Szabó Hydrogen sulphide and its therapeutic potential Nat Rev Drug Discov 6 2007 917 935
123. Y. Tanaka, N. Shigemura, T. Kawamura, K. Noda, K. Isse, and D.B. Stolz et al. Profiling molecular changes induced by hydrogen treatment of lung allografts prior to procurement Biochem Biophys Res Commun 425 2012 873 879
124. H. Tanriverdi, H. Evrengul, O. Kuru, S. Tanriverdi, D. Seleci, and Y. Enli et al. Cigarette smoking induced oxidative stress may impair endothelial function and coronary blood flow in angiographically normal coronary arteries Circ J 70 2006 593 599
125. Y. Terasaki, I. Ohsawa, M. Terasaki, M. Takahashi, S. Kunugi, and K. Dedong et al. Hydrogen therapy attenuates irradiation-induced lung damage by reducing oxidative stress Am J Physiol Lung Cell Mol Physiol 301 2011 L415 L426
126. K.V. Tormos, E. Anso, R.B. Hamanaka, J. Eisenbart, J. Joseph, and B. Kalyanaraman et al. Mitochondrial complex III ROS regulate adipocyte differentiation Cell Metab 14 2011 537 544
127. H. Tsukagoshi, W. Busch, and P.N. Benfey Transcriptional regulation of ROS controls transition from proliferation to differentiation in the root Cell 143 2010 606 616
128. J.F. Turrens Mitochondrial formation of reactive oxygen species J Physiol 552 2003 335 344
129. N.D. Vaziri, and B. Rodriguez-Iturbe Mechanisms of disease: oxidative stress and inflammation in the pathogenesis of hypertension Nat Clin Pract Nephrol 2 2006 582 593
130. F. Wang, G. Yu, S.Y. Liu, J.B. Li, J.F. Wang, and L.L. Bo et al. Hydrogen-rich saline protects against renal ischemia/reperfusion injury in rats J Surg Res 167 2011 e339 e344
131. A.P. West, I.E. Brodsky, C. Rahner, D.K. Woo, H. Erdjument-Bromage, and P. Tempst et al. TLR signalling augments macrophage bactericidal activity through mitochondrial ROS Nature 472 2011 476 480
132. H. Westerblad, and D.G. Allen Emerging roles of ROS/RNS in muscle function and fatigue Antioxid Redox Signal 15 2011 2487 2499
133. K. Xie, Y. Yu, Y. Pei, L. Hou, S. Chen, and L. Xiong et al. Protective effects of hydrogen gas on murine polymicrobial sepsis via reducing oxidative stress and HMGB1 release Shock 34 2010 90 97
134. K. Xie, Y. Yu, Z. Zhang, W. Liu, Y. Pei, and L. Xiong et al. Hydrogen gas improves survival rate and organ damage in zymosan-induced generalized inflammation model Shock 34 2010 495 501
135. Z. Xu, J. Zhou, J. Cai, Z. Zhu, X. Sun, and C. Jiang Anti-inflammation effects of hydrogen saline in LPS activated macrophages and carrageenan induced paw oedema J Inflamm (Lond) 9 2012 2
136. A. Yoritaka, N. Hattori, K. Uchida, M. Tanaka, E.R. Stadtman, and Y. Mizuno Immunohistochemical detection of 4-hydroxynonenal protein adducts in Parkinson disease Proc Natl Acad Sci U S A 93 1996 2696 2701
137. A. Yoritaka, M. Takanashi, M. Hirayama, T. Nakahara, S. Ohta, and N. Hattori Pilot study of H(2) therapy in Parkinson's disease: a randomized double-blind placebo-controlled trial Mov Disord 28 2013 836 839
138. A. Yoshida, H. Asanuma, H. Sasaki, S. Sanada, S. Yamazaki, and Y. Asano et al. H(2) mediates cardioprotection via involvements of K(ATP) channels and permeability transition pores of mitochondria in dogs Cardiovasc Drugs Ther 26 2012 217 226
139. P. Yu, Z. Wang, X. Sun, X. Chen, S. Zeng, and L. Chen et al. Hydrogen-rich medium protects human skin fibroblasts from high glucose or mannitol induced oxidative damage Biochem Biophys Res Commun 409 2011 350 355
140. X. Zhai, X. Chen, J. Shi, D. Shi, Z. Ye, and W. Liu et al. Lactulose ameliorates cerebral ischemia-reperfusion injury in ratsby inducing hydrogen by activating Nrf2 expression Free Radic Biol Med 65 2013 731 741
141. Y. Zhang, Q. Sun, B. He, J. Xiao, Z. Wang, and X. Sun Anti-inflammatory effect of hydrogen-rich saline in a rat model of regional myocardial ischemia and reperfusion Int J Cardiol 148 2011 91 95
142. H. Zhou, Z. Fu, Y. Wei, J. Liu, X. Cui, and W. Yang et al. Hydrogen inhalation decreases lung graft injury in brain-dead donor rats J Heart Lung Transplant 32 2013 251 258
143. R. Zhou, A.S. Yazdi, P. Menu, and J. Tschopp A role for mitochondria in NLRP3 inflammasome activation Nature 469 2011 221 225
144. W.J. Zhu, M. Nakayama, T. Mori, K. Nakayama, J. Katoh, and Y. Murata et al. Intake of water with high levels of dissolved hydrogen (H2) suppresses ischemia-induced cardio-renal injury in Dahl salt-sensitive rats Nephrol Dial Transplant 26 2011 2112 2118