Generic placeholder image

Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Mechanisms Underlying the Biological Effects of Molecular Hydrogen

Author(s): Svetlana N. Radyuk*

Volume 27, Issue 5, 2021

Published on: 11 December, 2020

Page: [626 - 735] Pages: 110

DOI: 10.2174/1381612826666201211112846

Price: $65


Aberrant redox-sensitive reactions and accumulation of oxidative damage can impair body functions and contribute to the development of various pathologies and aging. Although antioxidant substances have long been recognized as a measure of alleviating oxidative stress and restoring redox balance, the arsenal of effective means of preventing the development of various disorders, is still limited. There is an emerging field that utilizes molecular hydrogen (H2) as a scavenger of free radicals and reactive oxygen species (ROS). Among the remarkable characteristics of H2 is its ability to counteract the harmful effects of hydroxyl radical and peroxynitrite without affecting the activity of functionally important ROS, such as hydrogen peroxide and nitric oxide. The beneficial effects of H2 have been documented in numerous clinical studies and studies on animal models and cell cultures. However, the established scavenging activity of H2 can only partially explain its beneficial effects because the effects are achieved at very low concentrations of H2. Given the rate of H2 diffusion, such low concentrations may not be sufficient to scavenge continuously generated ROS. H2 can also act as a signaling molecule and induce defense responses. However, the exact targets and mechanism(s) by which H2 exerts these effects are unknown. Here, we analyzed both positive and negative effects of the endogenous H2, identified the redox-sensitive components of the pathways affected by molecular hydrogen, and also discussed the potential role of molecular hydrogen in regulating cellular redox.

Keywords: Antioxidant, cellular redox, endogenous hydrogen gas, inflammation, molecular hydrogen, oxidative stress, reactive oxygen species, redox signaling.

Ostojic SM. Eumelanin-driven production of molecular hydrogen: A novel element of skin defense? Med Hypotheses 2015; 85(2): 237-8.
[] [PMID: 25920542]
Chuai Y, Qian L, Sun X, Cai J. Molecular hydrogen and radiation protection. Free Radic Res 2012; 46(9): 1061-7.
[] [PMID: 22537465]
Abraini JH, Gardette-Chauffour MC, Martinez E, Rostain JC, Lemaire C. Psychophysiological reactions in humans during an open sea dive to 500 m with a hydrogen-helium-oxygen mixture. J Appl Physiol (1985) 1994; 76(3): 1113-8.
Shen M, Zhang H, Yu C, Wang F, Sun X. A review of experimental studies of hydrogen as a new therapeutic agent in emergency and critical care medicine. Med Gas Res 2014; 4: 17.
[] [PMID: 25905011]
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; 2012353152
[] [PMID: 22720117]
Huang CS, Kawamura T, Toyoda Y, Nakao A. Recent advances in hydrogen research as a therapeutic medical gas. Free Radic Res 2010; 44(9): 971-82.
[] [PMID: 20815764]
Ge L, Yang M, Yang NN, Yin XX, Song WG. Molecular hydrogen: a preventive and therapeutic medical gas for various diseases. Oncotarget 2017; 8(60): 102653-73.
[] [PMID: 29254278]
Ohta S. Molecular hydrogen as a novel antioxidant: overview of the advantages of hydrogen for medical applications. Methods Enzymol 2015; 555: 289-317.
[] [PMID: 25747486]
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.
[] [PMID: 17486089]
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.
[] [PMID: 28890349]
Ohta S. Recent progress toward hydrogen medicine: potential of molecular hydrogen for preventive and therapeutic applications. Curr Pharm Des 2011; 17(22): 2241-52.
[] [PMID: 21736547]
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 2011; 1(1): 12.
[] [PMID: 22146068]
Hong Y, Chen S, Zhang JM. Hydrogen as a selective antioxidant: a review of clinical and experimental studies. J Int Med Res 2010; 38(6): 1893-903.
[] [PMID: 21226992]
Han AL, Park SH, Park MS. Hydrogen treatment protects against cell death and senescence induced by oxidative damage. J Microbiol Biotechnol 2017; 27(2): 365-71.
[] [PMID: 27780950]
Ichihara M, Sobue S, Ito M, Ito M, Hirayama M, Ohno K. Beneficial biological effects and the underlying mechanisms of molecular hydrogen - comprehensive review of 321 original articles. Med Gas Res 2015; 5: 12.
[] [PMID: 26483953]
Sauer H, Wartenberg M, Hescheler J. Reactive oxygen species as intracellular messengers during cell growth and differentiation. Cell Physiol Biochem 2001; 11(4): 173-86.
[] [PMID: 11509825]
Kikkawa YS, Nakagawa T, Horie RT, Ito J. Hydrogen protects auditory hair cells from free radicals. Neuroreport 2009; 20(7): 689-94.
[] [PMID: 19339905]
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
[] [PMID: 28467497]
Kawasaki H, Guan J, Tamama K. Hydrogen gas treatment prolongs replicative lifespan of bone marrow multipotential stromal cells in vitro while preserving differentiation and paracrine potentials. Biochem Biophys Res Commun 2010; 397(3): 608-13.
[] [PMID: 20570654]
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.
[] [PMID: 19766097]
Yu J, Yu Q, Liu Y, Zhang R, Xue L. Hydrogen gas alleviates oxygen toxicity by reducing hydroxyl radical levels in PC12 cells. PLoS One 2017; 12(3)e0173645
[] [PMID: 28362819]
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.
[] [PMID: 18541148]
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.
[] [PMID: 21293445]
Vignais PM, Billoud B. Occurrence, classification, and biological function of hydrogenases: an overview. Chem Rev 2007; 107(10): 4206-72.
[] [PMID: 17927159]
Kalantar-Zadeh K, Berean KJ, Burgell RE, Muir JG, Gibson PR. Intestinal gases: influence on gut disorders and the role of dietary manipulations. Nat Rev Gastroenterol Hepatol 2019; 16(12): 733-47.
[] [PMID: 31520080]
Sankar P, Shanmugam KT. Biochemical and genetic analysis of hydrogen metabolism in Escherichia coli: the hydB gene. J Bacteriol 1988; 170(12): 5433-9.
[] [PMID: 2848007]
Hasegawa S, Goto S, Tsuji H, et al. Intestinal dysbiosis and lowered serum lipopolysaccharide-binding protein in Parkinson’s disease. PLoS One 2015; 10(11)e0142164
[] [PMID: 26539989]
Hylemon PB, Harris SC, Ridlon JM. Metabolism of hydrogen gases and bile acids in the gut microbiome. FEBS Lett 2018; 592(12): 2070-82.
[] [PMID: 29683480]
Suzuki A, Ito M, Hamaguchi T, et al. Quantification of hydrogen production by intestinal bacteria that are specifically dysregulated in Parkinson’s disease. PLoS One 2018; 13(12)e0208313
[] [PMID: 30586410]
Carbonero F, Benefiel AC, Gaskins HR. Contributions of the microbial hydrogen economy to colonic homeostasis. Nat Rev Gastroenterol Hepatol 2012; 9(9): 504-18.
[] [PMID: 22585131]
Di Stefano M, Mengoli C, Bergonzi M, Pagani E, Corazza GR. Hydrogen breath test and intestinal gas production. Eur Rev Med Pharmacol Sci 2013; 17(Suppl. 2): 36-8.
[PMID: 24443066]
Wolin MJ, Miller TL. Bacterial strains from human feces that reduce CO2 to acetic acid. Appl Environ Microbiol 1993; 59(11): 3551-6.
[] [PMID: 8285662]
Bond JH Jr, Levitt MD, Prentiss R. Investigation of small bowel transit time in man utilizing pulmonary hydrogen (H2) measurements. J Lab Clin Med 1975; 85(4): 546-55.
[PMID: 1120927]
Huang C, Zeng G, Xia F, Xiao Y. Study on the relative absorption of food carbohydrate in healthy adults. Wei Sheng Yan Jiu 1998; 27(3): 175-9.
[PMID: 10684125]
Zhai S, Zhu L, Qin S, Li L. Effect of lactulose intervention on gut microbiota and short chain fatty acid composition of C57BL/6J mice. MicrobiologyOpen 2018; 7(6)e00612
[] [PMID: 29575825]
Xie Y, Li W, Zhu L, Zhai S, Qin S, Du Z. Effects of phycocyanin in modulating the intestinal microbiota of mice. MicrobiologyOpen 2019; 8(9)e00825
[] [PMID: 30912299]
Pimentel M, Chow EJ, Lin HC. Eradication of small intestinal bacterial overgrowth reduces symptoms of irritable bowel syndrome. Am J Gastroenterol 2000; 95(12): 3503-6.
[] [PMID: 11151884]
Jung SE, Joo NS, Han KS, Kim KN. Obesity is inversely related to hydrogen-producing small intestinal bacterial overgrowth in non-constipation irritable bowel syndrome. J Korean Med Sci 2017; 32(6): 948-53.
[] [PMID: 28480652]
Lee SH, Cho DY, Joo NS, Kim KN. Effect of eradicating hydrogen-forming small intestinal bacterial overgrowth with rifaximin on body weight change. Medicine (Baltimore) 2019; 98(51)e18396
[] [PMID: 31861004]
McKay LF, Holbrook WP, Eastwood MA. Methane and hydrogen production by human intestinal anaerobic bacteria. Acta Pathol Microbiol Immunol Scand [B] 1982; 90(3): 257-60.
[] [PMID: 6289602]
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.
[] [PMID: 31996394]
Olson JW, Maier RJ. Molecular hydrogen as an energy source for Helicobacter pylori. Science 2002; 298(5599): 1788-90.
[] [PMID: 12459589]
Kuhns LG, Benoit SL, Bayyareddy K, et al. Carbon fixation driven by molecular hydrogen results in chemolithoautotrophically enhanced growth of Helicobacter pylori. J Bacteriol 2016; 198(9): 1423-8.
[] [PMID: 26929299]
Maier RJ. Availability and use of molecular hydrogen as an energy substrate for Helicobacter species. Microbes Infect 2003; 5(12): 1159-63.
[] [PMID: 14554258]
Maier RJ. Use of molecular hydrogen as an energy substrate by human pathogenic bacteria. Biochem Soc Trans 2005; 33(Pt 1): 83-5.
[] [PMID: 15667272]
Lamichhane-Khadka R, Benoit SL, Maier SE, Maier RJ. A link between gut community metabolism and pathogenesis: molecular hydrogen-stimulated glucarate catabolism aids Salmonella virulence. Open Biol 2013; 3(12)130146
[] [PMID: 24307595]
Higashimura Y, Baba Y, Inoue R, et al. Effects of molecular hydrogen-dissolved alkaline electrolyzed water on intestinal environment in mice. Med Gas Res 2018; 8(1): 6-11.
[] [PMID: 29770190]
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.
[] [PMID: 19523450]
Nishimura N, Tanabe H, Komori E, Sasaki Y, Inoue R, Yamamoto T. Transplantation of high hydrogen-producing microbiota leads to generation of large amounts of colonic hydrogen in recipient rats fed high amylose maize starch. Nutrients 2018; 10(2)E144
[] [PMID: 29382125]
Kawashima M, Tsuno S, Matsumoto M, Tsubota K. Hydrogen-producing milk to prevent reduction in tear stability in persons using visual display terminals. Ocul Surf 2019; 17(4): 714-21.
[] [PMID: 31352083]
Ito M, Hirayama M, Yamai K, et al. Drinking hydrogen water and intermittent hydrogen gas exposure, but not lactulose or continuous hydrogen gas exposure, prevent 6-hydorxydopamine-induced Parkinson’s disease in rats. Med Gas Res 2012; 2(1): 15.
[] [PMID: 22608009]
Eriksen JL, Wszolek Z, Petrucelli L. Molecular pathogenesis of Parkinson disease. Arch Neurol 2005; 62(3): 353-7.
[] [PMID: 15767499]
Erro R, Brigo F, Tamburin S, Zamboni M, Antonini A, Tinazzi M. Nutritional habits, risk, and progression of Parkinson disease. J Neurol 2018; 265(1): 12-23.
[] [PMID: 29018983]
Forsyth CB, Shannon KM, Kordower JH, et al. Increased intestinal permeability correlates with sigmoid mucosa alpha-synuclein staining and endotoxin exposure markers in early Parkinson’s disease. PLoS One 2011; 6(12)e28032
[] [PMID: 22145021]
Ostojic SM. Inadequate Production of H2 by Gut microbiota and Parkinson disease. Trends Endocrinol Metab 2018; 29(5): 286-8.
[] [PMID: 29478695]
Huang HK, Wang JH, Lei WY, Chen CL, Chang CY, Liou LS. Helicobacter pylori infection is associated with an increased risk of Parkinson’s disease: A population-based retrospective cohort study. Parkinsonism Relat Disord 2018; 47: 26-31.
[] [PMID: 29174171]
Tan AH, Mahadeva S, Marras C, et al. Helicobacter pylori infection is associated with worse severity of Parkinson’s disease. Parkinsonism Relat Disord 2015; 21(3): 221-5.
[] [PMID: 25560322]
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
[] [PMID: 19789628]
Noda M, Uemura Y, Yoshii Y, et al. Circulating messenger for neuroprotection induced by molecular hydrogen. Can J Physiol Pharmacol 2019; 97(10): 909-15.
[] [PMID: 31100203]
Matsumoto A, Yamafuji M, Tachibana T, Nakabeppu Y, Noda M, Nakaya H. Oral ‘hydrogen water’ induces neuroprotective ghrelin secretion in mice. Sci Rep 2013; 3: 3273.
[] [PMID: 24253616]
Engelstoft MS, Park WM, Sakata I, et al. Seven transmembrane G protein-coupled receptor repertoire of gastric ghrelin cells. Mol Metab 2013; 2(4): 376-92.
[] [PMID: 24327954]
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.
[] [PMID: 28462451]
Bai J, Yang F, Dong L, Zheng Y. Ghrelin protects human lens epithelial cells against oxidative stress-induced damage. Oxid Med Cell Longev 2017; 20171910450
[] [PMID: 29129986]
El Zein N, Abdallah MS, Daher CF, et al. Ghrelin modulates intracellular signalling pathways that are critical for podocyte survival. Cell Biochem Funct 2019; 37(4): 245-55.
[] [PMID: 31017709]
Wu G, Pan L, Sun J, Chen G, Wang S. Hydrogen gas protects against ovariectomy-induced osteoporosis by inhibiting NF-κB activation. Menopause 2019; 26(7): 785-92.
[] [PMID: 31083022]
Yu Y, Yang Y, Bian Y, et al. Hydrogen gas protects against intestinal injury in wild type but not NRF2 knockout mice with severe sepsis by regulating HO-1 and HMGB1 release. Shock 2017; 48(3): 364-70.
[] [PMID: 28234792]
Qiu P, Liu Y, Zhang J. Recent advances in studies of molecular hydrogen against sepsis. Int J Biol Sci 2019; 15(6): 1261-75.
[] [PMID: 31223285]
Xie K, Liu L, Yu Y, Wang G. Hydrogen gas presents a promising therapeutic strategy for sepsis. BioMed Res Int 2014; 2014807635
[] [PMID: 24829918]
Zheng Y, Zhu D. Molecular Hydrogen therapy ameliorates organ damage induced by sepsis. Oxid Med Cell Longev 2016; 20165806057
[] [PMID: 27413421]
Wang P, Zhao M, Chen Z, et al. Hydrogen gas attenuates hypoxic-ischemic brain injury via regulation of the MAPK/HO-1/PGC-1a pathway in neonatal rats. Oxid Med Cell Longev 2020; 20206978784
[] [PMID: 32104537]
Chen H, Mao X, Meng X, et al. Hydrogen alleviates mitochondrial dysfunction and organ damage via autophagy mediated NLRP3 inflammasome inactivation in sepsis. Int J Mol Med 2019; 44(4): 1309-24.
[] [PMID: 31432098]
LeBaron TW, Kura B, Kalocayova B, Tribulova N, Slezak J. A New approach for the prevention and treatment of cardiovascular disorders. molecular hydrogen significantly reduces the effects of oxidative stress. Molecules 2019; 24(11)E2076
[] [PMID: 31159153]
Mei K, Zhao S, Qian L, Li B, Ni J, Cai J. Hydrogen protects rats from dermatitis caused by local radiation. J Dermatolog Treat 2014; 25(2): 182-8.
[] [PMID: 23273331]
Sano M, Suzuki M, Homma K, et al. Promising novel therapy with hydrogen gas for emergency and critical care medicine. Acute Med Surg 2017; 5(2): 113-8.
[] [PMID: 29657720]
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
[] [PMID: 29371696]
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.
[] [PMID: 30543459]
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.
[] [PMID: 22146004]
Kawamura T, Higashida K, Muraoka I. Application of molecular hydrogen as a novel antioxidant in sports science. Oxid Med Cell Longev 2020; 20202328768
[] [PMID: 32015786]
Ostojic SM. Molecular hydrogen in sports medicine: new therapeutic perspectives. Int J Sports Med 2015; 36(4): 273-9.
[PMID: 25525953]
Zhu Q, Wu Y, Li Y, et al. Positive effects of hydrogen-water bathing in patients of psoriasis and parapsoriasis en plaques. Sci Rep 2018; 8(1): 8051.
[] [PMID: 29795283]
Cejka C, Kubinova S, Cejkova J. The preventive and therapeutic effects of molecular hydrogen in ocular diseases and injuries where oxidative stress is involved. Free Radic Res 2019; 53(3): 237-47.
[] [PMID: 30773939]
Zhang Y, Li H, Yang C, et al. Treatment with hydrogen-rich saline delays disease progression in a mouse model of amyotrophic lateral sclerosis. Neurochem Res 2016; 41(4): 770-8.
[] [PMID: 26537817]
Huang L. Molecular hydrogen: a therapeutic antioxidant and beyond. Med Gas Res 2016; 6(4): 219-22.
[] [PMID: 28217294]
Ghanizadeh A, Berk M. Molecular hydrogen: an overview of its neurobiological effects and therapeutic potential for bipolar disorder and schizophrenia. Med Gas Res 2013; 3(1): 11.
[] [PMID: 23742229]
Ishibashi T. Therapeutic efficacy of molecular hydrogen: a new mechanistic insight. Curr Pharm Des 2019; 25(9): 946-55.
[] [PMID: 31057105]
Ishibashi T. Molecular hydrogen: new antioxidant and anti-inflammatory therapy for rheumatoid arthritis and related diseases. Curr Pharm Des 2013; 19(35): 6375-81.
[] [PMID: 23859555]
Ohta S. Molecular hydrogen is a novel antioxidant to efficiently reduce oxidative stress with potential for the improvement of mitochondrial diseases. Biochim Biophys Acta 2012; 1820(5): 586-94.
[] [PMID: 21621588]
Guan P, Sun ZM, Luo LF, et al. Hydrogen gas alleviates chronic intermittent hypoxia-induced renal injury through reducing iron overload. Molecules 2019; 24(6)E1184
[] [PMID: 30917568]
Haam S, Lee JG, Paik HC, Park MS, Lim BJ. Hydrogen gas inhalation during ex vivo lung perfusion of donor lungs recovered after cardiac death. J Heart Lung Transplant 2018; 37(10): 1271-8.
[] [PMID: 30100327]
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.
[] [PMID: 30710119]
Yao HT, Yang YH, Li ML. Intake of Molecular hydrogen in drinking water increases membrane transporters, p-glycoprotein, and multidrug resistance-associated protein 2 without affecting xenobiotic-metabolizing enzymes in rat liver. Molecules 2019; 24(14)E2627
[] [PMID: 31330936]
Hasegawa S, Ito M, Fukami M, Hashimoto M, Hirayama M, Ohno K. Molecular hydrogen alleviates motor deficits and muscle degeneration in mdx mice. Redox Rep 2017; 22(1): 26-34.
[] [PMID: 26866650]
Sohal RS, Orr WC. The redox stress hypothesis of aging. Free Radic Biol Med 2012; 52(3): 539-55.
[] [PMID: 22080087]
Ray PD, Huang BW, Tsuji Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal 2012; 24(5): 981-90.
[] [PMID: 22286106]
Dröge W. Redox regulation in anabolic and catabolic processes. Curr Opin Clin Nutr Metab Care 2006; 9(3): 190-5.
[] [PMID: 16607115]
Stapper ZA, Jahn TR. Changes in glutathione redox potential are linked to Aβ42-induced neurotoxicity. Cell Rep 2018; 24(7): 1696-703.
[] [PMID: 30110626]
D’Ambrosi N, Cozzolino M, Carrì MT. Neuroinflammation in amyotrophic lateral sclerosis: role of redox (dys)regulation. Antioxid Redox Signal 2018; 29(1): 15-36.
[] [PMID: 28895473]
Go YM, Jones DP. Redox theory of aging: implications for health and disease. Clin Sci (Lond) 2017; 131(14): 1669-88.
[] [PMID: 28667066]
Lei Y, Wang K, Deng L, Chen Y, Nice EC, Huang C. Redox regulation of inflammation: old elements, a new story. Med Res Rev 2015; 35(2): 306-40.
[] [PMID: 25171147]
Abais JM, Xia M, Zhang Y, Boini KM, Li PL. Redox regulation of NLRP3 inflammasomes: ROS as trigger or effector? Antioxid Redox Signal 2015; 22(13): 1111-29.
[] [PMID: 25330206]
Yin F, Boveris A, Cadenas E. Mitochondrial energy metabolism and redox signaling in brain aging and neurodegeneration. Antioxid Redox Signal 2014; 20(2): 353-71.
[] [PMID: 22793257]
Shaukat Z, Liu DW, Gregory S. Sterile Inflammation in Drosophila. Mediat Inflamm 2015; 2015369826
Heneka MT, Kummer MP, Latz E. Innate immune activation in neurodegenerative disease. Nat Rev Immunol 2014; 14(7): 463-77.
[] [PMID: 24962261]
Fougère B, Boulanger E, Nourhashémi F, Guyonnet S, Cesari M. Chronic Inflammation: Accelerator of Biological Aging. J Gerontol A Biol Sci Med Sci 2017; 72(9): 1218-25.
[] [PMID: 28003373]
Bektas A, Schurman SH, Sen R, Ferrucci L. Aging, inflammation and the environment. Exp Gerontol 2017; 105: 10-8.
[PMID: 29275161]
Fourquet S, Guerois R, Biard D, Toledano MB. Activation of NRF2 by nitrosative agents and H2O2 involves KEAP1 disulfide formation. J Biol Chem 2010; 285(11): 8463-71.
[] [PMID: 20061377]
Hourihan JM, Kenna JG, Hayes JD. The gasotransmitter hydrogen sulfide induces nrf2-target genes by inactivating the keap1 ubiquitin ligase substrate adaptor through formation of a disulfide bond between cys-226 and cys-613. Antioxid Redox Signal 2013; 19(5): 465-81.
[] [PMID: 23145493]
Holland R, Hawkins AE, Eggler AL, Mesecar AD, Fabris D, Fishbein JC. Prospective type 1 and type 2 disulfides of Keap1 protein. Chem Res Toxicol 2008; 21(10): 2051-60.
[] [PMID: 18729328]
Pantano C, Reynaert NL, van der Vliet A, Janssen-Heininger YM. Redox-sensitive kinases of the nuclear factor-kappaB signaling pathway. Antioxid Redox Signal 2006; 8(9-10): 1791-806.
[] [PMID: 16987032]
Kabe Y, Ando K, Hirao S, Yoshida M, Handa H. Redox regulation of NF-kappaB activation: distinct redox regulation between the cytoplasm and the nucleus. Antioxid Redox Signal 2005; 7(3-4): 395-403.
[] [PMID: 15706086]
Lin YC, Huang GD, Hsieh CW, Wung BS. The glutathionylation of p65 modulates NF-kappaB activity in 15-deoxy-Delta(1)(2),(1)(4)-prostaglandin J(2)-treated endothelial cells. Free Radic Biol Med 2012; 52(9): 1844-53.
[] [PMID: 22387200]
Circu ML, Aw TY. Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic Biol Med 2010; 48(6): 749-62.
[] [PMID: 20045723]
Koehler CM, Beverly KN, Leverich EP. Redox pathways of the mitochondrion. Antioxid Redox Signal 2006; 8(5-6): 813-22.
[] [PMID: 16771672]
Yim MB, Chae HZ, Rhee SG, Chock PB, Stadtman ER. On the protective mechanism of the thiol-specific antioxidant enzyme against the oxidative damage of biomacromolecules. J Biol Chem 1994; 269(3): 1621-6.
[PMID: 8294408]
Forman HJ, Maiorino M, Ursini F. Signaling functions of reactive oxygen species. Biochemistry 2010; 49(5): 835-42.
[] [PMID: 20050630]
Park M, Steinberg SF. Carvedilol prevents redox inactivation of cardiomyocyte β1-adrenergic receptors. JACC Basic Transl Sci 2018; 3(4): 521-32.
[] [PMID: 30175276]
Warne T, Edwards PC, Leslie AG, Tate CG. Crystal structures of a stabilized β1-adrenoceptor bound to the biased agonists bucindolol and carvedilol. Structure 2012; 20(5): 841-9.
[] [PMID: 22579251]
Johnson WM, Yao C, Siedlak SL, et al. Glutaredoxin deficiency exacerbates neurodegeneration in C. elegans models of Parkinson’s disease. Hum Mol Genet 2014; 24(5): 1322-35.
[PMID: 25355420]
Rodriguez-Rocha H, Garcia Garcia A, Zavala-Flores L, Li S, Madayiputhiya N, Franco R. Glutaredoxin 1 protects dopaminergic cells by increased protein glutathionylation in experimental Parkinson’s disease. Antioxid Redox Signal 2012; 17(12): 1676-93.
[] [PMID: 22816731]
Yun HM, Choi DY, Oh KW, Hong JT. PRDX6 Exacerbates Dopaminergic Neurodegeneration in a MPTP Mouse Model of Parkinson’s Disease. Mol Neurobiol 2015; 52(1): 422-31.
[] [PMID: 25193021]
Klichko VI, Safonov VL, Safonov MY, Radyuk SN. Supplementation with hydrogen-producing composition confers beneficial effects on physiology and life span in Drosophila. Heliyon 2019; 5(5)e01679
[] [PMID: 31193183]
Radyuk SN, Orr WC. The multifaceted impact of peroxiredoxins on aging and disease. Antioxid Redox Signal 2018; 29(13): 1293-311.
[] [PMID: 29212351]
Dubuisson M, Vander Stricht D, Clippe A, et al. Human peroxiredoxin 5 is a peroxynitrite reductase. FEBS Lett 2004; 571(1-3): 161-5.
[] [PMID: 15280035]
Cui W, Yao P, Pan J, et al. Transcriptome analysis reveals insight into molecular hydrogen-induced cadmium tolerance in alfalfa: the prominent role of sulfur and (homo)glutathione metabolism. BMC Plant Biol 2020; 20(1): 58.
[] [PMID: 32019510]
Chrestensen CA, Starke DW, Mieyal JJ. Acute cadmium exposure inactivates thioltransferase (Glutaredoxin), inhibits intracellular reduction of protein-glutathionyl-mixed disulfides, and initiates apoptosis. J Biol Chem 2000; 275(34): 26556-65.
[] [PMID: 10854441]
Vido K, Spector D, Lagniel G, Lopez S, Toledano MB, Labarre J. A proteome analysis of the cadmium response in Saccharomyces cerevisiae. J Biol Chem 2001; 276(11): 8469-74.
[] [PMID: 11078740]
Liu J, Qu W, Kadiiska MB. Role of oxidative stress in cadmium toxicity and carcinogenesis. Toxicol Appl Pharmacol 2009; 238(3): 209-14.
[] [PMID: 19236887]
Wu CY, Hsu WL, Tsai MH, et al. Hydrogen gas protects IP3Rs by reducing disulfide bridges in human keratinocytes under oxidative stress. Sci Rep 2017; 7(1): 3606.
[] [PMID: 28620198]
Tu BP, Weissman JS. Oxidative protein folding in eukaryotes: mechanisms and consequences. J Cell Biol 2004; 164(3): 341-6.
[] [PMID: 14757749]
Malhotra JD, Kaufman RJ. Endoplasmic reticulum stress and oxidative stress: a vicious cycle or a double-edged sword? Antioxid Redox Signal 2007; 9(12): 2277-93.
[] [PMID: 17979528]
Klichko VI, Orr WC, Radyuk SN. The role of peroxiredoxin 4 in inflammatory response and aging. Biochim Biophys Acta 2016; 1862(2): 265-73.
[] [PMID: 26689888]
Chaudhari N, Talwar P, Parimisetty A, Lefebvre d’Hellencourt C, Ravanan P. A molecular web: endoplasmic reticulum stress, inflammation, and oxidative stress. Front Cell Neurosci 2014; 8: 213.
[] [PMID: 25120434]
Hasnain SZ, Lourie R, Das I, Chen AC, McGuckin MA. The interplay between endoplasmic reticulum stress and inflammation. Immunol Cell Biol 2012; 90(3): 260-70.
[] [PMID: 22249202]
Hoozemans JJ, Veerhuis R, Van Haastert ES, et al. The unfolded protein response is activated in Alzheimer’s disease. Acta Neuropathol 2005; 110(2): 165-72.
[] [PMID: 15973543]
Koss DJ, Platt B. Alzheimer's disease pathology and the unfolded protein response: prospective pathways and therapeutic targets Behav Pharmacol 2017; 28(2 and 3 - Special Issue): 161-78.
Honjo Y, Ayaki T, Tomiyama T, et al. Decreased levels of PDI and P5 in oligodendrocytes in Alzheimer’s disease. Neuropathology 2017; 37(6): 495-501.
[] [PMID: 28731225]
Xu C, Bailly-Maitre B, Reed JC. Endoplasmic reticulum stress: cell life and death decisions. J Clin Invest 2005; 115(10): 2656-64.
[] [PMID: 16200199]
Viana RJ, Nunes AF, Rodrigues CM. Endoplasmic reticulum enrollment in Alzheimer’s disease. Mol Neurobiol 2012; 46(2): 522-34.
[] [PMID: 22815194]
Wang L, Ryoo HD, Qi Y, Jasper H. PERK Limits drosophila lifespan by promoting intestinal stem cell proliferation in response to ER stress. PLoS Genet 2015; 11(5)e1005220
[] [PMID: 25945494]
Wang J, Pareja KA, Kaiser CA, Sevier CS. Redox signaling via the molecular chaperone BiP protects cells against endoplasmic reticulum-derived oxidative stress. eLife 2014; 3e03496
[] [PMID: 25053742]
Gao Y, Yang H, Chi J, et al. Hydrogen gas attenuates myocardial ischemia reperfusion injury independent of postconditioning in rats by attenuating endoplasmic reticulum stress-induced autophagy. Cell Physiol Biochem 2017; 43(4): 1503-14.
[] [PMID: 29035876]
Bai X, Liu S, Yuan L, et al. Hydrogen-rich saline mediates neuroprotection through the regulation of endoplasmic reticulum stress and autophagy under hypoxia-ischemia neonatal brain injury in mice. Brain Res 2016; 1646: 410-7.
[] [PMID: 27317636]
Song G, Zong C, Zhang Z, et al. Molecular hydrogen stabilizes atherosclerotic plaque in low-density lipoprotein receptor-knockout mice. Free Radic Biol Med 2015; 87: 58-68.
[] [PMID: 26117323]

Rights & Permissions Print Export Cite as
© 2023 Bentham Science Publishers | Privacy Policy