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Review Article

Protective Effects of Hydrogen against Irradiation

Author(s): Yasuhiro Terasaki*, Mika Terasaki and Akira Shimizu

Volume 27, Issue 5, 2021

Published on: 19 January, 2021

Page: [679 - 686] Pages: 8

DOI: 10.2174/1381612827666210119103545

Price: $65

Abstract

Radiation-induced lung injury is characterized by an acute pneumonia phase followed by a fibrotic phase. At the time of irradiation, a rapid, short-lived burst of reactive oxygen species (ROS) such as hydroxyl radicals (•OH) occurs, but chronic radiation-induced lung injury may occur due to excess ROS such as H2O2, O2•−, ONOO−, and •OH. Molecular hydrogen (H2) is an efficient antioxidant that quickly diffuses cell membranes, reduces ROS such as •OH and ONOO−, and suppresses damage caused by oxidative stress in various organs. In 2011, through the evaluation of electron-spin resonance and fluorescent indicator signals, we had reported that H2 can eliminate •OH and can protect against oxidative stress-related apoptotic damage induced by irradiation of cultured lung epithelial cells. We had explored for the first time the radioprotective effects of H2 treatment on acute and chronic radiation-induced lung damage in mice by inhaled H2 gas (for acute) and imbibed H2-enriched water (for chronic). Thus, we had proposed that H2 be considered a potential radioprotective agent. Recent publications have shown that H2 directly neutralizes highly reactive oxidants and indirectly reduces oxidative stress by regulating the expression of various genes. By regulating gene expression, H2 functions as an anti-inflammatory and anti-apoptotic molecule and promotes energy metabolism. The increased evidence obtained from cultured cells or animal experiments reveal a putative place for H2 treatment and its radioprotective effect clinically. This review focuses on major scientific advances in the treatment of H2 as a new class of radioprotective agents.

Keywords: Apoptosis, reactive oxygen species, hydroxyl radical, peroxynitrite, free radical scavengers, radioprotective.

« Previous Next »
[1]
Singh VK, Seed TM. Pharmacological management of ionizing radiation injuries: current and prospective agents and targeted organ systems. Expert Opin Pharmacother 2020; 21(3): 317-37.
[http://dx.doi.org/10.1080/14656566.2019.1702968] [PMID: 31928256]
[2]
Riley PA. Free radicals in biology: oxidative stress and the effects of ionizing radiation. Int J Radiat Biol 1994; 65(1): 27-33.
[http://dx.doi.org/10.1080/09553009414550041] [PMID: 7905906]
[3]
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]
[4]
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]
[5]
Fukuda K, Asoh S, Ishikawa M, Yamamoto Y, Ohsawa I, Ohta S. Inhalation of hydrogen gas suppresses hepatic injury caused by ischemia/reperfusion through reducing oxidative stress. Biochem Biophys Res Commun 2007; 361(3): 670-4.
[http://dx.doi.org/10.1016/j.bbrc.2007.07.088] [PMID: 17673169]
[6]
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]
[7]
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]
[8]
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]
[9]
Qian L, Cao F, Cui J, et al. Radioprotective effect of hydrogen in cultured cells and mice. Free Radic Res 2010; 44(3): 275-82.
[http://dx.doi.org/10.3109/10715760903468758] [PMID: 20166892]
[10]
Qian L, Cao F, Cui J, et al. The potential cardioprotective effects of hydrogen in irradiated mice. J Radiat Res (Tokyo) 2010; 51(6): 741-7.
[http://dx.doi.org/10.1269/jrr.10093] [PMID: 21116102]
[11]
Chuai Y, Qian L, Sun X, Cai J. Molecular hydrogen and radiation protection. Free Radic Res 2012; 46(9): 1061-7.
[http://dx.doi.org/10.3109/10715762.2012.689429] [PMID: 22537465]
[12]
Watanabe S, Fujita M, Ishihara M, et al. Protective effect of inhalation of hydrogen gas on radiation-induced dermatitis and skin injury in rats. J Radiat Res (Tokyo) 2014; 55(6): 1107-13.
[http://dx.doi.org/10.1093/jrr/rru067] [PMID: 25034733]
[13]
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]
[14]
Kura B, Kalocayova B, LeBaron TW, et al. Regulation of microRNAs by molecular hydrogen contributes to the prevention of radiation-induced damage in the rat myocardium. Mol Cell Biochem 2019; 457(1-2): 61-72.
[http://dx.doi.org/10.1007/s11010-019-03512-z] [PMID: 30830529]
[15]
Ward JF. DNA damage produced by ionizing radiation in mammalian cells: identities, mechanisms of formation, and reparability. Prog Nucleic Acid Res Mol Biol 1988; 35: 95-125.
[http://dx.doi.org/10.1016/S0079-6603(08)60611-X] [PMID: 3065826]
[16]
Zhao W, Robbins ME. Inflammation and chronic oxidative stress in radiation-induced late normal tissue injury: therapeutic implications. Curr Med Chem 2009; 16(2): 130-43.
[http://dx.doi.org/10.2174/092986709787002790] [PMID: 19149566]
[17]
Stadtman ER. Oxidation of free amino acids and amino acid residues in proteins by radiolysis and by metal-catalyzed reactions. Annu Rev Biochem 1993; 62: 797-821.
[http://dx.doi.org/10.1146/annurev.bi.62.070193.004053] [PMID: 8352601]
[18]
Mishra KP. Cell membrane oxidative damage induced by gamma-radiation and apoptotic sensitivity. J Environ Pathol Toxicol Oncol 2004; 23(1): 61-6.
[http://dx.doi.org/10.1615/JEnvPathToxOncol.v23.i1.60] [PMID: 14994996]
[19]
Dubner D, Gisone P, Jaitovich I, Perez M. Free radicals production and estimation of oxidative stress related to gamma irradiation. Biol Trace Elem Res 1995; 47(1-3): 265-70.
[http://dx.doi.org/10.1007/BF02790126] [PMID: 7779556]
[20]
Giusti AM, Raimondi M, Ravagnan G, Sapora O, Parasassi T. Human cell membrane oxidative damage induced by single and fractionated doses of ionizing radiation: a fluorescence spectroscopy study. Int J Radiat Biol 1998; 74(5): 595-605.
[http://dx.doi.org/10.1080/095530098141177] [PMID: 9848278]
[21]
Pohl LR. An immunochemical approach of identifying and characterizing protein targets of toxic reactive metabolites. Chem Res Toxicol 1993; 6(6): 786-93.
[http://dx.doi.org/10.1021/tx00036a006] [PMID: 8117916]
[22]
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]
[23]
Para AE, Bezjak A, Yeung IW, Van Dyk J, Hill RP. Effects of genistein following fractionated lung irradiation in mice. Radiother Oncol 2009; 92(3): 500-10.
[http://dx.doi.org/10.1016/j.radonc.2009.04.005] [PMID: 19433340]
[24]
Deeg HJ. Seattle Marrow Transplant Team. Acute and delayed toxicities of total body irradiation. Int J Radiat Oncol Biol Phys 1983; 9(12): 1933-9.
[http://dx.doi.org/10.1016/0360-3016(83)90365-6] [PMID: 9463096]
[25]
Sampath S, Schultheiss TE, Wong J. Dose response and factors related to interstitial pneumonitis after bone marrow transplant. Int J Radiat Oncol Biol Phys 2005; 63(3): 876-84.
[http://dx.doi.org/10.1016/j.ijrobp.2005.02.032] [PMID: 16199317]
[26]
Beyzadeoglu M, Oysul K, Dirican B, et al. Effect of dose-rate and lung dose in total body irradiation on interstitial pneumonitis after bone marrow transplantation. Tohoku J Exp Med 2004; 202(4): 255-63.
[http://dx.doi.org/10.1620/tjem.202.255] [PMID: 15109123]
[27]
Hopewell JW. The skin: its structure and response to ionizing radiation. Int J Radiat Biol 1990; 57(4): 751-73.
[http://dx.doi.org/10.1080/09553009014550911] [PMID: 1969905]
[28]
Nagatani K, Nawashiro H, Takeuchi S, et al. Safety of intravenous administration of hydrogen-enriched fluid in patients with acute cerebral ischemia: initial clinical studies. Med Gas Res 2013; 3: 13.
[http://dx.doi.org/10.1186/2045-9912-3-13] [PMID: 23799921]
[29]
Liu C, Kurokawa R, Fujino M, Hirano S, Sato B, Li XK. Estimation of the hydrogen concentration in rat tissue using an airtight tube following the administration of hydrogen via various routes. Sci Rep 2014; 4: 5485.
[http://dx.doi.org/10.1038/srep05485] [PMID: 24975958]
[30]
Potten CS. Extreme sensitivity of some intestinal crypt cells to X and gamma irradiation. Nature 1977; 269(5628): 518-21.
[http://dx.doi.org/10.1038/269518a0] [PMID: 909602]
[31]
Grande T, Bueren JA. The mobilization of hematopoietic progenitors to peripheral blood is predictive of the hematopoietic syndrome after total or partial body irradiation of mice. Int J Radiat Oncol Biol Phys 2006; 64(2): 612-8.
[http://dx.doi.org/10.1016/j.ijrobp.2005.09.036] [PMID: 16414374]
[32]
Chuai Y, Shen J, Qian L, et al. Hydrogen-rich saline protects spermatogenesis and hematopoiesis in irradiated BALB/c mice. Med Sci Monit 2012; 18(3): BR89-94.
[http://dx.doi.org/10.12659/MSM.882513] [PMID: 22367121]
[33]
Oakberg EF. Sensitivity and time of degeneration of spermatogenic cells irradiated in various stages of maturation in the mouse. Radiat Res 1955; 2(4): 369-91.
[http://dx.doi.org/10.2307/3570245] [PMID: 14385033]
[34]
Chuai Y, Gao F, Li B, et al. Hydrogen-rich saline attenuates radiation-induced male germ cell loss in mice through reducing hydroxyl radicals. Biochem J 2012; 442(1): 49-56.
[http://dx.doi.org/10.1042/BJ20111786] [PMID: 22077489]
[35]
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]
[36]
Shimouchi A, Nose K, Shirai M, Kondo T. Estimation of molecular hydrogen consumption in the human whole body after the ingestion of hydrogen-rich water. Adv Exp Med Biol 2012; 737: 245-50.
[http://dx.doi.org/10.1007/978-1-4614-1566-4_36] [PMID: 22259109]
[37]
McDonald S, Rubin P, Phillips TL, Marks LB. Injury to the lung from cancer therapy: clinical syndromes, measurable endpoints, and potential scoring systems. Int J Radiat Oncol Biol Phys 1995; 31(5): 1187-203.
[http://dx.doi.org/10.1016/0360-3016(94)00429-O] [PMID: 7713782]
[38]
Fleckenstein K, Zgonjanin L, Chen L, et al. Temporal onset of hypoxia and oxidative stress after pulmonary irradiation. Int J Radiat Oncol Biol Phys 2007; 68(1): 196-204.
[http://dx.doi.org/10.1016/j.ijrobp.2006.12.056] [PMID: 17448873]
[39]
Leach JK, Van Tuyle G, Lin PS, Schmidt-Ullrich R, Mikkelsen RB. Ionizing radiation-induced, mitochondria-dependent generation of reactive oxygen/nitrogen. Cancer Res 2001; 61(10): 3894-901.
[PMID: 11358802]
[40]
Li F, Sonveaux P, Rabbani ZN, et al. Regulation of HIF-1alpha stability through S-nitrosylation. Mol Cell 2007; 26(1): 63-74.
[http://dx.doi.org/10.1016/j.molcel.2007.02.024] [PMID: 17434127]
[41]
Mikkelsen RB, Wardman P. Biological chemistry of reactive oxygen and nitrogen and radiation-induced signal transduction mechanisms. Oncogene 2003; 22(37): 5734-54.
[http://dx.doi.org/10.1038/sj.onc.1206663] [PMID: 12947383]
[42]
Machtay M, Scherpereel A, Santiago J, et al. Systemic polyethylene glycol-modified (PEGylated) superoxide dismutase and catalase mixture attenuates radiation pulmonary fibrosis in the C57/bl6 mouse. Radiother Oncol 2006; 81(2): 196-205.
[http://dx.doi.org/10.1016/j.radonc.2006.09.013] [PMID: 17069914]
[43]
Lee JC, Krochak R, Blouin A, et al. Dietary flaxseed prevents radiation-induced oxidative lung damage, inflammation and fibrosis in a mouse model of thoracic radiation injury. Cancer Biol Ther 2009; 8(1): 47-53.
[http://dx.doi.org/10.4161/cbt.8.1.7092] [PMID: 18981722]
[44]
Schultz-Hector S. Radiation-induced heart disease: review of experimental data on dose response and pathogenesis. Int J Radiat Biol 1992; 61(2): 149-60.
[http://dx.doi.org/10.1080/09553009214550761] [PMID: 1351901]
[45]
Lee CK, Aeppli D, Nierengarten ME. The need for long-term surveillance for patients treated with curative radiotherapy for Hodgkin’s disease: University of Minnesota experience. Int J Radiat Oncol Biol Phys 2000; 48(1): 169-79.
[http://dx.doi.org/10.1016/S0360-3016(00)00647-7] [PMID: 10924987]
[46]
Lauk S. Endothelial alkaline phosphatase activity loss as an early stage in the development of radiation-induced heart disease in rats. Radiat Res 1987; 110(1): 118-28.
[http://dx.doi.org/10.2307/3576889] [PMID: 3562789]
[47]
Ono H, Nishijima Y, Adachi N, 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 A non-controlled study 2011; 1(1) 12
[48]
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]
[49]
Song G, Li M, Sang H, et al. Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome. J Lipid Res 2013; 54(7): 1884-93.
[http://dx.doi.org/10.1194/jlr.M036640] [PMID: 23610159]
[50]
Ishibashi T, Sato B, Rikitake M, 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 2012; 2(1): 27.
[http://dx.doi.org/10.1186/2045-9912-2-27] [PMID: 23031079]
[51]
Kang KM, Kang YN, Choi IB, et al. Effects of drinking hydrogen-rich water on the quality of life of patients treated with radiotherapy for liver tumors. Med Gas Res 2011; 1(1): 11.
[http://dx.doi.org/10.1186/2045-9912-1-11] [PMID: 22146004]
[52]
Buxton GV, Mulazzani QG, Ross AB. Critical review of rate constants for reactions of transients from metal ions and metal complexes in aqueous solution. J Phys Chem Ref Data 1995; 24(3): 1055-349.
[http://dx.doi.org/10.1063/1.555966]
[53]
Wood KC, Gladwin MT. The hydrogen highway to reperfusion therapy. Nat Med 2007; 13(6): 673-4.
[http://dx.doi.org/10.1038/nm0607-673] [PMID: 17554332]
[54]
Niki E. Lipid peroxidation: physiological levels and dual biological effects. Free Radic Biol Med 2009; 47(5): 469-84.
[http://dx.doi.org/10.1016/j.freeradbiomed.2009.05.032] [PMID: 19500666]
[55]
Jiang Z, Xu B, Yang M, Li Z, Zhang Y, Jiang D. Protection by hydrogen against gamma ray-induced testicular damage in rats. Basic Clin Pharmacol Toxicol 2013; 112(3): 186-91.
[http://dx.doi.org/10.1111/bcpt.12016] [PMID: 22998562]
[56]
Radi R. Peroxynitrite, a stealthy biological oxidant. J Biol Chem 2013; 288(37): 26464-72.
[http://dx.doi.org/10.1074/jbc.R113.472936] [PMID: 23861390]
[57]
Cardinal JS, Zhan J, Wang Y, et al. Oral hydrogen water prevents chronic allograft nephropathy in rats. Kidney Int 2010; 77(2): 101-9.
[http://dx.doi.org/10.1038/ki.2009.421] [PMID: 19907413]
[58]
Shinbo T, Kokubo K, Sato Y, et al. Breathing nitric oxide plus hydrogen gas reduces ischemia-reperfusion injury and nitrotyrosine production in murine heart. Am J Physiol Heart Circ Physiol 2013; 305(4): H542-50.
[http://dx.doi.org/10.1152/ajpheart.00844.2012] [PMID: 23771690]
[59]
Chen CH, Manaenko A, Zhan Y, et al. Hydrogen gas reduced acute hyperglycemia-enhanced hemorrhagic transformation in a focal ischemia rat model. Neuroscience 2010; 169(1): 402-14.
[http://dx.doi.org/10.1016/j.neuroscience.2010.04.043] [PMID: 20423721]
[60]
Zhang Y, Sun Q, He B, Xiao J, Wang Z, Sun X. Anti-inflammatory effect of hydrogen-rich saline in a rat model of regional myocardial ischemia and reperfusion. Int J Cardiol 2011; 148(1): 91-5.
[http://dx.doi.org/10.1016/j.ijcard.2010.08.058] [PMID: 20851484]
[61]
Hanaue N, Takeda I, Kizu Y, Tonogi M, Yamane GY. Peroxynitrite formation in radiation-induced salivary gland dysfunction in mice. Biomed Res 2007; 28(3): 147-51.
[http://dx.doi.org/10.2220/biomedres.28.147] [PMID: 17625347]
[62]
Giaid A, Lehnert SM, Chehayeb B, Chehayeb D, Kaplan I, Shenouda G. Inducible nitric oxide synthase and nitrotyrosine in mice with radiation-induced lung damage. Am J Clin Oncol 2003; 26(4): e67-72.
[http://dx.doi.org/10.1097/01.COC.0000077940.05196.86] [PMID: 12902901]
[63]
Tsuji C, Shioya S, Hirota Y, et al. Increased production of nitrotyrosine in lung tissue of rats with radiation-induced acute lung injury. Am J Physiol Lung Cell Mol Physiol 2000; 278(4): L719-25.
[http://dx.doi.org/10.1152/ajplung.2000.278.4.L719] [PMID: 10749749]
[64]
Jiang Y, Liu G, Zhang L, et al. Therapeutic efficacy of hydrogen rich saline alone and in combination with PI3K inhibitor in non small cell lung cancer. Mol Med Rep 2018; 18(2): 2182-90.
[http://dx.doi.org/10.3892/mmr.2018.9168] [PMID: 29901139]
[65]
Chen H, Zhang J, Hao H, et al. Hydrogen-rich water increases postharvest quality by enhancing antioxidant capacity in Hypsizygus marmoreus. AMB Express 2017; 7(1): 221.
[http://dx.doi.org/10.1186/s13568-017-0496-9] [PMID: 29264772]
[66]
Kura B, Bagchi AK, Singal PK, et al. Molecular hydrogen: potential in mitigating oxidative-stress-induced radiation injury. Can J Physiol Pharmacol 2019; 97(4): 287-92.
[http://dx.doi.org/10.1139/cjpp-2018-0604] [PMID: 30543459]
[67]
Nakao A, Toyoda Y, Sharma P, Evans M, Guthrie N. Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome-an open label pilot study. J Clin Biochem Nutr 2010; 46(2): 140-9.
[http://dx.doi.org/10.3164/jcbn.09-100] [PMID: 20216947]
[68]
Nakai Y, Sato B, Ushiama S, Okada S, Abe K, Arai S. Hepatic oxidoreduction-related genes are upregulated by administration of hydrogen-saturated drinking water. Biosci Biotechnol Biochem 2011; 75(4): 774-6.
[http://dx.doi.org/10.1271/bbb.100819] [PMID: 21512236]
[69]
Hara F, Tatebe J, Watanabe I, Yamazaki J, Ikeda T, Morita T. Molecular hydrogen alleviates cellular senescence in endothelial cells. Circ J 2016; 80(9): 2037-46.
[http://dx.doi.org/10.1253/circj.CJ-16-0227] [PMID: 27477846]
[70]
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]
[71]
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]
[72]
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]
[73]
Li GM, Ji MH, Sun XJ, et al. Effects of hydrogen-rich saline treatment on polymicrobial sepsis. J Surg Res 2013; 181(2): 279-86.
[http://dx.doi.org/10.1016/j.jss.2012.06.058] [PMID: 22795273]

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