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Review Article

Biological Responses to Hydrogen Molecule and its Preventive Effects on Inflammatory Diseases

Author(s): Ikuroh Ohsawa*

Volume 27, Issue 5, 2021

Published on: 25 September, 2020

Page: [659 - 666] Pages: 8

DOI: 10.2174/1381612826666200925123510

Price: $65

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Abstract

Because multicellular organisms do not have hydrogenase, H2 has been considered to be biologically inactive in these species, and enterobacteria to be largely responsible for the oxidation of H2 taken into the body. However, we showed previously that inhalation of H2 markedly suppresses brain injury induced by focal ischemia-reperfusion by buffering oxidative stress. Although the reaction constant of H2 with hydroxyl radical in aqueous solution is two to three orders of magnitude lower than that of conventional antioxidants, we showed that hydroxyl radical generated by the Fenton reaction reacts with H2 at room temperature without a catalyst. Suppression of hydroxyl radical by H2 has been applied in ophthalmic surgery. However, many of the anti- inflammatory and other therapeutic effects of H2 cannot be completely explained by its ability to scavenge reactive oxygen species. H2 administration is protective in several disease models, and preculture in the presence of H2 suppresses oxidative stress-induced cell death. Specifically, H2 administration induces mitochondrial oxidative stress and activates Nrf2; this phenomenon, in which mild mitochondrial stress leaves the cell less susceptible to subsequent perturbations, is called mitohormesis. Based on these findings, we conclude that crosstalk between antioxidative stress pathways and the anti-inflammatory response is the most important molecular mechanism involved in the protective function of H2, and that regulation of the immune system underlies H2 efficacy. For further medical applications of H2, it will be necessary to identify the biomolecule on which H2 first acts.

Keywords: Hydroxyl radical, immune system, inflammation, ischemia-reperfusion, mitohormesis, molecular hydrogen, noncommunicable disease, reductant.

« Previous Next »
[1]
Iketani M, Ohsawa I. Molecular hydrogen as a neuroprotective agent. Curr Neuropharmacol 2017; 15(2): 324-31.
[http://dx.doi.org/10.2174/1570159X14666160607205417] [PMID: 27281176]
[2]
Ohsawa I, Ishikawa M, Takahashi K, et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med 2007; 13(6): 688-94.
[http://dx.doi.org/10.1038/nm1577] [PMID: 17486089]
[3]
Fu Y, Ito M, Fujita Y, et al. Molecular hydrogen is protective against 6-hydroxydopamine-induced nigrostriatal degeneration in a rat model of Parkinson’s disease. Neurosci Lett 2009; 453(2): 81-5.
[http://dx.doi.org/10.1016/j.neulet.2009.02.016] [PMID: 19356598]
[4]
Fujita K, Seike T, Yutsudo N, 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 2009; 4(9): e7247.
[http://dx.doi.org/10.1371/journal.pone.0007247] [PMID: 19789628]
[5]
Yoritaka A, Takanashi M, Hirayama M, Nakahara T, Ohta S, Hattori N. Pilot study of H2 therapy in Parkinson’s disease: a randomized double-blind placebo-controlled trial. Mov Disord 2013; 28(6): 836-9.
[http://dx.doi.org/10.1002/mds.25375] [PMID: 23400965]
[6]
Nishimaki K, Asada T, Ohsawa I, et al. Effects of molecular hydrogen assessed by an animal model and a randomized clinical study on mild cognitive impairment. Curr Alzheimer Res 2018; 15(5): 482-92.
[http://dx.doi.org/10.2174/1567205014666171106145017] [PMID: 29110615]
[7]
Ohta S. Molecular hydrogen as a novel antioxidant: overview of the advantages of hydrogen for medical applications. Methods Enzymol 2015; 555: 289-317.
[http://dx.doi.org/10.1016/bs.mie.2014.11.038] [PMID: 25747486]
[8]
Nakano T, Kotani T, Mano Y, et al. Maternal molecular hydrogen administration on lipopolysaccharide-induced mouse fetal brain injury. J Clin Biochem Nutr 2015; 57(3): 178-82.
[http://dx.doi.org/10.3164/jcbn.15-90] [PMID: 26566302]
[9]
Ren JD, Wu XB, Jiang R, Hao DP, Liu Y. Molecular hydrogen inhibits lipopolysaccharide-triggered NLRP3 inflammasome activation in macrophages by targeting the mitochondrial reactive oxygen species. Biochim Biophys Acta 2016; 1863(1): 50-5.
[http://dx.doi.org/10.1016/j.bbamcr.2015.10.012] [PMID: 26488087]
[10]
Xie K, Yu Y, Huang Y, et al. Molecular hydrogen ameliorates lipopolysaccharide-induced acute lung injury in mice through reducing inflammation and apoptosis. Shock 2012; 37(5): 548-55.
[http://dx.doi.org/10.1097/SHK.0b013e31824ddc81] [PMID: 22508291]
[11]
Kajiya M, Sato K, Silva MJ, et al. Hydrogen from intestinal bacteria is protective for Concanavalin A-induced hepatitis. Biochem Biophys Res Commun 2009; 386(2): 316-21.
[http://dx.doi.org/10.1016/j.bbrc.2009.06.024] [PMID: 19523450]
[12]
Kajiya M, Silva MJ, Sato K, Ouhara K, Kawai T. Hydrogen mediates suppression of colon inflammation induced by dextran sodium sulfate. Biochem Biophys Res Commun 2009; 386(1): 11-5.
[http://dx.doi.org/10.1016/j.bbrc.2009.05.117] [PMID: 19486890]
[13]
Shen NY, Bi JB, Zhang JY, et al. Hydrogen-rich water protects against inflammatory bowel disease in mice by inhibiting endoplasmic reticulum stress and promoting heme oxygenase-1 expression. World J Gastroenterol 2017; 23(8): 1375-86.
[http://dx.doi.org/10.3748/wjg.v23.i8.1375] [PMID: 28293084]
[14]
Ohno K, Ito M, Ichihara M, Ito M. Molecular hydrogen as an emerging therapeutic medical gas for neurodegenerative and other diseases. Oxid Med Cell Longev 2012; 2012: 353152.
[http://dx.doi.org/10.1155/2012/353152] [PMID: 22720117]
[15]
Benoit SL, Maier RJ, Sawers RG, Greening C. Molecular hydrogen metabolism: a widespread trait of pathogenic bacteria and protists. Microbiol Mol Biol Rev 2020; 84(1): e00092-19.
[http://dx.doi.org/10.1128/MMBR.00092-19] [PMID: 31996394]
[16]
Levitt MD, Bond JH Jr. Volume, composition, and source of intestinal gas. Gastroenterology 1970; 59(6): 921-9.
[http://dx.doi.org/10.1016/S0016-5085(19)33654-6] [PMID: 5486278]
[17]
Shimouchi A, Nose K, Mizukami T, Che DC, Shirai M. Molecular hydrogen consumption in the human body during the inhalation of hydrogen gas. Adv Exp Med Biol 2013; 789: 315-21.
[http://dx.doi.org/10.1007/978-1-4614-7411-1_42] [PMID: 23852510]
[18]
Sano M, Ichihara G, Katsumata Y, et al. Pharmacokinetics of a single inhalation of hydrogen gas in pigs. PLoS One 2020; 15(6): e0234626.
[http://dx.doi.org/10.1371/journal.pone.0234626] [PMID: 32559239]
[19]
Pinson EA, Langham WH. Physiology and toxicology of tritium in man. J Appl Physiol 1957; 10(1): 108-26.
[http://dx.doi.org/10.1152/jappl.1957.10.1.108] [PMID: 13405839]
[20]
Ichimasa Y, Shiba H, Ichimasa M, Akita Y. Suppression of tritium gas oxidation in rat by norfloxacin and clindamycin. Int J Radiat Biol 1995; 67(4): 481-5.
[http://dx.doi.org/10.1080/09553009514550561] [PMID: 7738413]
[21]
Chan PH. Role of oxidants in ischemic brain damage. Stroke 1996; 27(6): 1124-9.
[http://dx.doi.org/10.1161/01.STR.27.6.1124] [PMID: 8650725]
[22]
Sokolova IM, Sokolov EP, Haider F. Mitochondrial mechanisms underlying tolerance to fluctuating oxygen conditions: lessons from hypoxia-tolerant organisms. Integr Comp Biol 2019; 59(4): 938-52.
[http://dx.doi.org/10.1093/icb/icz047] [PMID: 31120535]
[23]
Li C, Jackson RM. Reactive species mechanisms of cellular hypoxia-reoxygenation injury. Am J Physiol Cell Physiol 2002; 282(2): C227-41.
[http://dx.doi.org/10.1152/ajpcell.00112.2001] [PMID: 11788333]
[24]
Qian W, Kumar N, Roginskaya V, et al. Chemoptogenetic damage to mitochondria causes rapid telomere dysfunction. Proc Natl Acad Sci USA 2019; 116(37): 18435-44.
[http://dx.doi.org/10.1073/pnas.1910574116] [PMID: 31451640]
[25]
Ames BN. Dietary carcinogens and anticarcinogens. Oxygen radicals and degenerative diseases. Science 1983; 221(4617): 1256-64.
[http://dx.doi.org/10.1126/science.6351251] [PMID: 6351251]
[26]
Rice-Evans C, Burdon R. Free radical-lipid interactions and their pathological consequences. Prog Lipid Res 1993; 32(1): 71-110.
[http://dx.doi.org/10.1016/0163-7827(93)90006-I] [PMID: 8415800]
[27]
Lin MT, Beal MF. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 2006; 443(7113): 787-95.
[http://dx.doi.org/10.1038/nature05292] [PMID: 17051205]
[28]
Nagatani K, Wada K, Takeuchi S, et al. Effect of hydrogen gas on the survival rate of mice following global cerebral ischemia. Shock 2012; 37(6): 645-52.
[http://dx.doi.org/10.1097/SHK.0b013e31824ed57c] [PMID: 22392146]
[29]
Huang Y, Xie K, Li J, et al. Beneficial effects of hydrogen gas against spinal cord ischemia-reperfusion injury in rabbits. Brain Res 2011; 1378: 125-36.
[http://dx.doi.org/10.1016/j.brainres.2010.12.071] [PMID: 21195696]
[30]
Huang G, Zhou J, Zhan W, et al. The neuroprotective effects of intraperitoneal injection of hydrogen in rabbits with cardiac arrest. Resuscitation 2013; 84(5): 690-5.
[http://dx.doi.org/10.1016/j.resuscitation.2012.10.018] [PMID: 23108240]
[31]
Oharazawa H, Igarashi T, Yokota T, 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 2010; 51(1): 487-92.
[http://dx.doi.org/10.1167/iovs.09-4089] [PMID: 19834032]
[32]
Osborne NN, Casson RJ, Wood JP, Chidlow G, Graham M, Melena J. Retinal ischemia: mechanisms of damage and potential therapeutic strategies. Prog Retin Eye Res 2004; 23(1): 91-147.
[http://dx.doi.org/10.1016/j.preteyeres.2003.12.001] [PMID: 14766318]
[33]
Ono H, Nishijima Y, Ohta S, et al. Hydrogen Gas Inhalation Treatment in Acute Cerebral Infarction: A Randomized Controlled Clinical Study on Safety and neuroprotection. J Stroke Cerebrovasc Dis 2017; 26(11): 2587-94.
[http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2017.06.012] [PMID: 28669654]
[34]
Katsumura Y. Application of radiation chemistry to nuclear technology.charged-particle and photon interactions with matters, chemical, physicochemical, and biological consequences with applications 2004; 697-727.
[35]
Terasaki Y, Ohsawa I, Terasaki M, et al. Hydrogen therapy attenuates irradiation-induced lung damage by reducing oxidative stress. Am J Physiol Lung Cell Mol Physiol 2011; 301(4): L415-26.
[http://dx.doi.org/10.1152/ajplung.00008.2011] [PMID: 21764987]
[36]
Merouani S, Hamdaoui O, Rezgui Y, Guemini M. Mechanism of the sonochemical production of hydrogen. Int J Hydrogen Energy 2015; 40: 4056-64.
[http://dx.doi.org/10.1016/j.ijhydene.2015.01.150]
[37]
Igarashi T, Ohsawa I, Kobayashi M, et al. Hydrogen prevents corneal endothelial damage in phacoemulsification cataract surgery. Sci Rep 2016; 6: 31190.
[http://dx.doi.org/10.1038/srep31190] [PMID: 27498755]
[38]
Igarashi T, Ohsawa I, Kobayashi M, et al. Effects of hydrogen in prevention of corneal endothelial damage during phacoemulsification: a prospective randomized clinical trial. Am J Ophthalmol 2019; 207: 10-7.
[http://dx.doi.org/10.1016/j.ajo.2019.04.014] [PMID: 31077667]
[39]
Iuchi K, Imoto A, Kamimura N, et al. Molecular hydrogen regulates gene expression by modifying the free radical chain reaction-dependent generation of oxidized phospholipid mediators. Sci Rep 2016; 6: 18971.
[http://dx.doi.org/10.1038/srep18971] [PMID: 26739257]
[40]
Sato Y, Kajiyama S, Amano A, et al. Hydrogen-rich pure water prevents superoxide formation in brain slices of vitamin C-depleted SMP30/GNL knockout mice. Biochem Biophys Res Commun 2008; 375(3): 346-50.
[http://dx.doi.org/10.1016/j.bbrc.2008.08.020] [PMID: 18706888]
[41]
Iketani M, Ohshiro J, Urushibara T, et al. Preadministration of hydrogen-rich water protects against lipopolysaccharide-induced sepsis and attenuates liver Injury. Shock 2017; 48(1): 85-93.
[http://dx.doi.org/10.1097/SHK.0000000000000810] [PMID: 27918369]
[42]
Yoshii Y, Inoue T, Uemura Y, et al. Complexity of stomach-brain interaction induced by molecular hydrogen in parkinson’s disease model mice. Neurochem Res 2017; 42(9): 2658-65.
[http://dx.doi.org/10.1007/s11064-017-2281-1] [PMID: 28462451]
[43]
Kawamura T, Wakabayashi N, Shigemura N, et al. Hydrogen gas reduces hyperoxic lung injury via the Nrf2 pathway in vivo. Am J Physiol Lung Cell Mol Physiol 2013; 304(10): L646-56.
[http://dx.doi.org/10.1152/ajplung.00164.2012] [PMID: 23475767]
[44]
Li L, Zhang X, Cui L, et al. Ursolic acid promotes the neuroprotection by activating Nrf2 pathway after cerebral ischemia in mice. Brain Res 2013; 1497: 32-9.
[http://dx.doi.org/10.1016/j.brainres.2012.12.032] [PMID: 23276496]
[45]
Guo H, Li MJ, Liu QQ, et al. Danhong injection attenuates ischemia/reperfusion-induced brain damage which is associating with Nrf2 levels in vivo and in vitro. Neurochem Res 2014; 39(9): 1817-24.
[http://dx.doi.org/10.1007/s11064-014-1384-1] [PMID: 25069640]
[46]
Han J, Wang M, Jing X, Shi H, Ren M, Lou H. (-)-Epigallocatechin gallate protects against cerebral ischemia-induced oxidative stress via Nrf2/ARE signaling. Neurochem Res 2014; 39(7): 1292-9.
[http://dx.doi.org/10.1007/s11064-014-1311-5] [PMID: 24792731]
[47]
Shi H, Jing X, Wei X, et al. S-allyl cysteine activates the Nrf2-dependent antioxidant response and protects neurons against ischemic injury in vitro and in vivo. J Neurochem 2015; 133(2): 298-308.
[http://dx.doi.org/10.1111/jnc.12986] [PMID: 25393425]
[48]
Meffert MK, Haley JE, Schuman EM, Schulman H, Madison DV. Inhibition of hippocampal heme oxygenase, nitric oxide synthase, and long-term potentiation by metalloporphyrins. Neuron 1994; 13(5): 1225-33.
[http://dx.doi.org/10.1016/0896-6273(94)90060-4] [PMID: 7524564]
[49]
Wang B, Cao W, Biswal S, Doré S. Carbon monoxide-activated Nrf2 pathway leads to protection against permanent focal cerebral ischemia. Stroke 2011; 42(9): 2605-10.
[http://dx.doi.org/10.1161/STROKEAHA.110.607101] [PMID: 21852618]
[50]
Yao Y, Miao W, Liu Z, et al. Dimethyl fumarate and monomethyl fumarate promote post-ischemic recovery in mice. Transl Stroke Res 2016; 7(6): 535-47.
[http://dx.doi.org/10.1007/s12975-016-0496-0] [PMID: 27614618]
[51]
Hou Y, Wang Y, He Q, et al. Nrf2 inhibits NLRP3 inflammasome activation through regulating Trx1/TXNIP complex in cerebral ischemia reperfusion injury. Behav Brain Res 2018; 336: 32-9.
[http://dx.doi.org/10.1016/j.bbr.2017.06.027] [PMID: 28851669]
[52]
Yu J, Zhang W, Zhang R, et al. Molecular hydrogen attenuates hypoxia/reoxygenation injury of intrahepatic cholangiocytes by activating Nrf2 expression. Toxicol Lett 2015; 238(3): 11-9.
[http://dx.doi.org/10.1016/j.toxlet.2015.08.010] [PMID: 26276082]
[53]
Murakami Y, Ito M, Ohsawa I. Molecular hydrogen protects against oxidative stress-induced SH-SY5Y neuroblastoma cell death through the process of mitohormesis. PLoS One 2017; 12(5): e0176992.
[http://dx.doi.org/10.1371/journal.pone.0176992] [PMID: 28467497]
[54]
Karwi QG, Jörg AR, Lopaschuk GD. Allosteric, transcriptional and post-translational control of mitochondrial energy metabolism. Biochem J 2019; 476(12): 1695-712.
[http://dx.doi.org/10.1042/BCJ20180617] [PMID: 31217327]
[55]
Sanderson TH, Reynolds CA, Kumar R, Przyklenk K, Hüttemann M. Molecular mechanisms of ischemia-reperfusion injury in brain: pivotal role of the mitochondrial membrane potential in reactive oxygen species generation. Mol Neurobiol 2013; 47(1): 9-23.
[http://dx.doi.org/10.1007/s12035-012-8344-z] [PMID: 23011809]
[56]
Yun J, Finkel T. Mitohormesis. Cell Metab 2014; 19(5): 757-66.
[http://dx.doi.org/10.1016/j.cmet.2014.01.011] [PMID: 24561260]
[57]
Quirós PM, Mottis A, Auwerx J. Mitonuclear communication in homeostasis and stress. Nat Rev Mol Cell Biol 2016; 17(4): 213-26.
[http://dx.doi.org/10.1038/nrm.2016.23] [PMID: 26956194]
[58]
Cox CS, McKay SE, Holmbeck MA, et al. Mitohormesis in mice via sustained basal activation of mitochondrial and antioxidant signaling. Cell Metab 2018; 28(5): 776-786.e5.
[http://dx.doi.org/10.1016/j.cmet.2018.07.011] [PMID: 30122556]
[59]
Bárcena C, Mayoral P, Quirós PM. Mitohormesis, an antiaging paradigm. Int Rev Cell Mol Biol 2018; 340: 35-77.
[http://dx.doi.org/10.1016/bs.ircmb.2018.05.002] [PMID: 30072093]
[60]
Sobue S, Inoue C, Hori F, Qiao S, Murate T, Ichihara M. Molecular hydrogen modulates gene expression via histone modification and induces the mitochondrial unfolded protein response. Biochem Biophys Res Commun 2017; 493(1): 318-24.
[http://dx.doi.org/10.1016/j.bbrc.2017.09.024] [PMID: 28890349]
[61]
Yoshida A, Asanuma H, Sasaki H, et al. H(2) mediates cardioprotection via involvements of K(ATP) channels and permeability transition pores of mitochondria in dogs. Cardiovasc Drugs Ther 2012; 26(3): 217-26.
[http://dx.doi.org/10.1007/s10557-012-6381-5] [PMID: 22527618]
[62]
Baxter GF, Ferdinandy P. Delayed preconditioning of myocardium: current perspectives. Basic Res Cardiol 2001; 96(4): 329-44.
[http://dx.doi.org/10.1007/s003950170041] [PMID: 11518189]
[63]
Gross ER, Peart JN, Hsu AK, Grover GJ, Gross GJ. K(ATP) opener-induced delayed cardioprotection: involvement of sarcolemmal and mitochondrial K(ATP) channels, free radicals and MEK1/2. J Mol Cell Cardiol 2003; 35(8): 985-92.
[http://dx.doi.org/10.1016/S0022-2828(03)00183-4] [PMID: 12878485]
[64]
Javadov S, Hunter JC, Barreto-Torres G, Parodi-Rullan R. Targeting the mitochondrial permeability transition: cardiac ischemia-reperfusion versus carcinogenesis. Cell Physiol Biochem 2011; 27(3-4): 179-90.
[http://dx.doi.org/10.1159/000327943] [PMID: 21471706]
[65]
Nagata K, Nakashima-Kamimura N, Mikami T, Ohsawa I, Ohta S. Consumption of molecular hydrogen prevents the stress-induced impairments in hippocampus-dependent learning tasks during chronic physical restraint in mice. Neuropsychopharmacology 2009; 34(2): 501-8.
[http://dx.doi.org/10.1038/npp.2008.95] [PMID: 18563058]
[66]
Ohsawa I, Nishimaki K, Yamagata K, Ishikawa M, Ohta S. Consumption of hydrogen water prevents atherosclerosis in apolipoprotein E knockout mice. Biochem Biophys Res Commun 2008; 377(4): 1195-8.
[http://dx.doi.org/10.1016/j.bbrc.2008.10.156] [PMID: 18996093]
[67]
Terasaki Y, Suzuki T, Tonaki K, et al. Molecular hydrogen attenuates gefitinib-induced exacerbation of naphthalene-evoked acute lung injury through a reduction in oxidative stress and inflammation. Lab Invest 2019; 99(6): 793-806.
[http://dx.doi.org/10.1038/s41374-019-0187-z] [PMID: 30710119]
[68]
Terasaki Y, Terasaki M, Kanazawa S, et al. Effect of H2 treatment in a mouse model of rheumatoid arthritis-associated interstitial lung disease. J Cell Mol Med 2019; 23(10): 7043-53.
[http://dx.doi.org/10.1111/jcmm.14603] [PMID: 31424157]
[69]
Kamimura N, Nishimaki K, Ohsawa I, Ohta S. Molecular hydrogen improves obesity and diabetes by inducing hepatic FGF21 and stimulating energy metabolism in db/db mice. Obesity (Silver Spring) 2011; 19(7): 1396-403.
[http://dx.doi.org/10.1038/oby.2011.6] [PMID: 21293445]
[70]
Nakashima-Kamimura N, Mori T, Ohsawa I, Asoh S, Ohta S. Molecular hydrogen alleviates nephrotoxicity induced by an anti-cancer drug cisplatin without compromising anti-tumor activity in mice. Cancer Chemother Pharmacol 2009; 64(4): 753-61.
[http://dx.doi.org/10.1007/s00280-008-0924-2] [PMID: 19148645]
[71]
Zhan Y, Chen C, Suzuki H, Hu Q, Zhi X, Zhang JH. Hydrogen gas ameliorates oxidative stress in early brain injury after subarachnoid hemorrhage in rats. Crit Care Med 2012; 40(4): 1291-6.
[http://dx.doi.org/10.1097/CCM.0b013e31823da96d] [PMID: 22336722]
[72]
Manaenko A, Lekic T, Ma Q, Zhang JH, Tang J. Hydrogen inhalation ameliorated mast cell-mediated brain injury after intracerebral hemorrhage in mice. Crit Care Med 2013; 41(5): 1266-75.
[http://dx.doi.org/10.1097/CCM.0b013e31827711c9] [PMID: 23388512]
[73]
Wang P, Geng J, Gao J, et al. Macrophage achieves self-protection against oxidative stress-induced ageing through the Mst-Nrf2 axis. Nat Commun 2019; 10(1): 755.
[http://dx.doi.org/10.1038/s41467-019-08680-6] [PMID: 30765703]
[74]
Schwartz JC. Histamine as a transmitter in brain. Life Sci 1975; 17(4): 503-17.
[http://dx.doi.org/10.1016/0024-3205(75)90083-1] [PMID: 241888]
[75]
Itoh T, Fujita Y, Ito M, et al. Molecular hydrogen suppresses FcepsilonRI-mediated signal transduction and prevents degranulation of mast cells. Biochem Biophys Res Commun 2009; 389(4): 651-6.
[http://dx.doi.org/10.1016/j.bbrc.2009.09.047] [PMID: 19766097]
[76]
Iio A, Ito M, Itoh T, et al. Molecular hydrogen attenuates fatty acid uptake and lipid accumulation through downregulating CD36 expression in HepG2 cells. Med Gas Res 2013; 3(1): 6.
[http://dx.doi.org/10.1186/2045-9912-3-6] [PMID: 23448206]
[77]
Iketani M, Sekimoto K, Igarashi T, et al. Administration of hydrogen-rich water prevents vascular aging of the aorta in LDL receptor-deficient mice. Sci Rep 2018; 8(1): 16822.
[http://dx.doi.org/10.1038/s41598-018-35239-0] [PMID: 30429524]
[78]
Holdt LM, Sass K, Gäbel G, Bergert H, Thiery J, Teupser D. Expression of Chr9p21 genes CDKN2B (p15(INK4b)), CDKN2A (p16(INK4a), p14(ARF)) and MTAP in human atherosclerotic plaque. Atherosclerosis 2011; 214(2): 264-70.
[http://dx.doi.org/10.1016/j.atherosclerosis.2010.06.029] [PMID: 20637465]
[79]
Rossman MJ, Kaplon RE, Hill SD, et al. Endothelial cell senescence with aging in healthy humans: prevention by habitual exercise and relation to vascular endothelial function. Am J Physiol Heart Circ Physiol 2017; 313(5): H890-5.
[http://dx.doi.org/10.1152/ajpheart.00416.2017] [PMID: 28971843]
[80]
Coppé JP, Patil CK, Rodier F, et al. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol 2008; 6(12): 2853-68.
[http://dx.doi.org/10.1371/journal.pbio.0060301] [PMID: 19053174]
[81]
Rodier F, Coppé JP, Patil CK, et al. Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion. Nat Cell Biol 2009; 11(8): 973-9.
[http://dx.doi.org/10.1038/ncb1909] [PMID: 19597488]
[82]
Xiao HW, Li Y, Luo D, et al. Hydrogen-water ameliorates radiation-induced gastrointestinal toxicity via MyD88's effects on the gut microbiota. Exp Mol Med 2018; 50(1): e433.
[http://dx.doi.org/10.1038/emm.2017.246] [PMID: 29371696]
[83]
Maglione PJ, Simchoni N, Cunningham-rundles C. Toll-like receptor signaling in primary immune deficiencies. Ann N Y Acad Sci 2015; 1356: 1-21.
[http://dx.doi.org/10.1111/nyas.12763] [PMID: 25930993]
[84]
Itoh T, Hamada N, Terazawa R, et al. Molecular hydrogen inhibits lipopolysaccharide/interferon γ-induced nitric oxide production through modulation of signal transduction in macrophages. Biochem Biophys Res Commun 2011; 411(1): 143-9.
[http://dx.doi.org/10.1016/j.bbrc.2011.06.116] [PMID: 21723254]
[85]
Newby AC. Metalloproteinase production from macrophages - a perfect storm leading to atherosclerotic plaque rupture and myocardial infarction. Exp Physiol 2016; 101(11): 1327-37.
[http://dx.doi.org/10.1113/EP085567] [PMID: 26969796]
[86]
Lundberg AM, Hansson GK. Innate immune signals in atherosclerosis. Clin Immunol 2010; 134(1): 5-24.
[http://dx.doi.org/10.1016/j.clim.2009.07.016] [PMID: 19740706]
[87]
Ghosh AK, O’Brien M, Mau T, Yung R. Toll-like receptor 4 (TLR4) deficient mice are protected from adipose tissue inflammation in aging. Aging (Albany NY) 2017; 9(9): 1971-82.
[http://dx.doi.org/10.18632/aging.101288] [PMID: 28898202]
[88]
Hayashida K, Sano M, Kamimura N, 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 2012; 1(5): e003459.
[http://dx.doi.org/10.1161/JAHA.112.003459] [PMID: 23316300]
[89]
Kobayashi EH, Suzuki T, Funayama R, et al. Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription. Nat Commun 2016; 7: 11624.
[http://dx.doi.org/10.1038/ncomms11624] [PMID: 27211851]
[90]
Hayashida K, Sano M, Ohsawa I, et al. Inhalation of hydrogen gas reduces infarct size in the rat model of myocardial ischemia-reperfusion injury. Biochem Biophys Res Commun 2008; 373(1): 30-5.
[http://dx.doi.org/10.1016/j.bbrc.2008.05.165] [PMID: 18541148]
[91]
Bjurstedt H, Severin G. The prevention of decompression sickness and nitrogen narcosis by the use of hydrogen as a substitute for nitrogen, the Arne Zetterstrôm method for deep-sea diving. Mil Surg (Wash) 1948; 103(2): 107-16.
[http://dx.doi.org/10.1093/milmed/103.2.107] [PMID: 18876410]

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