Hydrogen in the treatment of human diseasesScientific ResearchDOI: 10.1155/2020/8384742
Published on: 08/09/2023
Hydrogen: A Novel Option in Human Disease Treatment
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,” Journal of Applied Physiology, vol. 76, no. 3, pp. 1113–1118, 1994.
M. Dole, F. Wilson, and W. Fife, “Hyperbaric hydrogen therapy: a possible treatment for cancer,” Science, vol. 190, no. 4210, pp. 152–154, 1975.
I. Ohsawa, M. Ishikawa, K. Takahashi et al., “Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals,” Nature Medicine, vol. 13, no. 6, pp. 688–694, 2007.
M. Chen, J. Zhang, Y. Chen et al., “Hydrogen protects lung from hypoxia/re-oxygenation injury by reducing hydroxyl radical production and inhibiting inflammatory responses,” Scientific Reports, vol. 8, no. 1, p. 8004, 2018.
Y. Bi, Y. Zhu, M. Zhang et al., “Effect of shikonin on spinal cord injury in rats via regulation of HMGB1/TLR4/NF-kB signaling pathway,” Cellular Physiology and Biochemistry, vol. 43, no. 2, pp. 481–491, 2017.
Y. Gao, H. Yang, Y. Fan, L. Li, J. Fang, and W. Yang, “Hydrogen-rich saline attenuates cardiac and hepatic injury in doxorubicin rat model by inhibiting inflammation and apoptosis,” Mediators of Inflammation, vol. 2016, Article ID 1320365, 10 pages, 2016.
C. Liu, R. Kurokawa, M. Fujino, S. Hirano, B. Sato, and X. K. Li, “Estimation of the hydrogen concentration in rat tissue using an airtight tube following the administration of hydrogen via various routes,” Scientific Reports, vol. 4, no. 1, article 5485, 2015.
W. Liu, L. P. Shan, X. S. Dong, X. W. Liu, T. Ma, and Z. Liu, “Combined early fluid resuscitation and hydrogen inhalation attenuates lung and intestine injury,” World Journal of Gastroenterology, vol. 19, no. 4, pp. 492–502, 2013.
Y. Yu, Y. Yang, M. Yang, C. Wang, K. Xie, and Y. Yu, “Hydrogen gas reduces HMGB1 release in lung tissues of septic mice in an Nrf2/HO-1-dependent pathway,” International Immunopharmacology, vol. 69, pp. 11–18, 2019.
Y. Tanaka, N. Shigemura, T. Kawamura et al., “Profiling molecular changes induced by hydrogen treatment of lung allografts prior to procurement,” Biochemical and Biophysical Research Communications, vol. 425, no. 4, pp. 873–879, 2012.
C. S. Huang, T. Kawamura, S. Lee et al., “Hydrogen inhalation ameliorates ventilator-induced lung injury,” Critical Care, vol. 14, no. 6, article R234, 2010.
A. Manaenko, T. Lekic, Q. Ma, J. H. Zhang, and J. Tang, “Hydrogen inhalation ameliorated mast cell-mediated brain injury after intracerebral hemorrhage in mice,” Critical Care Medicine, vol. 41, no. 5, pp. 1266–1275, 2013.
D. Schmit, D. D. le, S. Heck et al., “Allergic airway inflammation induces migration of mast cell populations into the mouse airway,” Cell and Tissue Research, vol. 369, no. 2, pp. 331–340, 2017.
T. Kajisa, T. Yamaguchi, A. Hu, N. Suetake, and H. Kobayashi, “Hydrogen water ameliorates the severity of atopic dermatitis-like lesions and decreases interleukin-1β, interleukin-33, and mast cell infiltration in NC/Nga mice,” Saudi Medical Journal, vol. 38, no. 9, pp. 928–933, 2017.
L. Chen, C. Ma, Y. Bian et al., “Hydrogen treatment protects mice against chronic pancreatitis by restoring regulatory T cells loss,” Cellular Physiology and Biochemistry, vol. 44, no. 5, pp. 2005–2016, 2017.
M. Hirayama, M. Ito, T. Minato, A. Yoritaka, T. W. LeBaron, and K. Ohno, “Inhalation of hydrogen gas elevates urinary 8-hydroxy-2-deoxyguanine in Parkinson’s disease,” Medical Gas Research, vol. 8, no. 4, pp. 144–149, 2018.
S. Liu, K. Liu, Q. Sun et al., “Consumption of hydrogen water reduces paraquat-induced acute lung injury in rats,” Journal of Biomedicine & Biotechnology, vol. 2011, Article ID 305086, 7 pages, 2011.
Y.-S. Zhao, J. R. An, S. Yang et al., “Hydrogen and oxygen mixture to improve cardiac dysfunction and myocardial pathological changes induced by intermittent hypoxia in rats,” Oxidative Medicine and Cellular Longevity, vol. 2019, Article ID 7415212, 12 pages, 2019.
K. Ohno, M. Ito, M. Ichihara, and M. Ito, “Molecular hydrogen as an emerging therapeutic medical gas for neurodegenerative and other diseases,” Oxidative Medicine and Cellular Longevity, vol. 2012, Article ID 353152, 11 pages, 2012.
M. Ichihara, S. Sobue, M. Ito, M. Ito, M. Hirayama, and K. Ohno, “Beneficial biological effects and the underlying mechanisms of molecular hydrogen – comprehensive review of 321 original articles,” Medical Gas Research, vol. 5, no. 1, p. 12, 2015.
K. Iuchi, K. Nishimaki, N. Kamimura, and S. Ohta, “Molecular hydrogen suppresses free-radical-induced cell death by mitigating fatty acid peroxidation and mitochondrial dysfunction,” Canadian Journal of Physiology and Pharmacology, vol. 97, no. 10, pp. 999–1005, 2019.
K. Kohama, H. Yamashita, M. Aoyama-Ishikawa et al., “Hydrogen inhalation protects against acute lung injury induced by hemorrhagic shock and resuscitation,” Surgery, vol. 158, no. 2, pp. 399–407, 2015.
M. Diao, S. Zhang, L. Wu et al., “Hydrogen gas inhalation attenuates seawater instillation-induced acute lung injury via the Nrf2 pathway in rabbits,” Inflammation, vol. 39, no. 6, pp. 2029–2039, 2016.
T. Ishibashi, “Therapeutic efficacy of molecular hydrogen: a new mechanistic insight,” Current Pharmaceutical Design, vol. 25, no. 9, pp. 946–955, 2019.
Y. Gao, H. Yang, J. Chi et al., “Hydrogen gas attenuates myocardial ischemia reperfusion injury independent of postconditioning in rats by attenuating endoplasmic reticulum stress-induced autophagy,” Cellular Physiology and Biochemistry, vol. 43, no. 4, pp. 1503–1514, 2017.
H. Zhong, R. Song, Q. Pang et al., “Propofol inhibits parthanatos via ROS-ER-calcium-mitochondria signal pathway in vivo and vitro,” Cell Death & Disease, vol. 9, no. 10, pp. 932–932, 2018.
X. Chen, J. Cui, X. Zhai et al., “Inhalation of hydrogen of different concentrations ameliorates spinal cord injury in mice by protecting spinal cord neurons from apoptosis, oxidative injury and mitochondrial structure damages,” Cellular Physiology and Biochemistry, vol. 47, no. 1, pp. 176–190, 2018.
Q. Li, P. Yu, Q. Zeng et al., “Neuroprotective effect of hydrogen-rich saline in global cerebral ischemia/reperfusion rats: up-regulated Tregs and down-regulated miR-21, miR-210 and NF-κB expression,” Neurochemical Research, vol. 41, no. 10, pp. 2655–2665, 2016.
X. Ma, J. Wang, J. Li et al., “Loading MiR-210 in endothelial progenitor cells derived exosomes boosts their beneficial effects on hypoxia/reoxygeneation-injured human endothelial cells via protecting mitochondrial function,” Cellular Physiology and Biochemistry, vol. 46, no. 2, pp. 664–675, 2018.
R. K. Mutharasan, V. Nagpal, Y. Ichikawa, and H. Ardehali, “MicroRNA-210 is upregulated in hypoxic cardiomyocytes through Akt- and p53-dependent pathways and exerts cytoprotective effects,” Heart and Circulatory Physiology, vol. 301, no. 4, pp. H1519–H1530, 2011.
A. Yoritaka, M. Takanashi, M. Hirayama, T. Nakahara, S. Ohta, and N. Hattori, “Pilot study of H2 therapy in Parkinson’s disease: a randomized double-blind placebo-controlled trial,” Movement Disorders, vol. 28, no. 6, pp. 836–839, 2013.
Y. Murakami, M. Ito, and I. Ohsawa, “Molecular hydrogen protects against oxidative stress-induced SH-SY5Y neuroblastoma cell death through the process of mitohormesis,” PLoS One, vol. 12, no. 5, article e0176992, 2017.
J. Meng, P. Yu, H. Jiang et al., “Molecular hydrogen decelerates rheumatoid arthritis progression through inhibition of oxidative stress,” American Journal of Translational Research, vol. 8, no. 10, pp. 4472–4477, 2016.View at: Google Scholar
T. Ishibashi, “Molecular hydrogen: new antioxidant and anti-inflammatory therapy for rheumatoid arthritis and related diseases,” Current Pharmaceutical Design, vol. 19, no. 35, pp. 6375–6381, 2013.
M. Ito, T. Ibi, K. Sahashi, M. Ichihara, M. Ito, and K. Ohno, “Open-label trial and randomized, double-blind, placebo-controlled, crossover trial of hydrogen-enriched water for mitochondrial and inflammatory myopathies,” Medical Gas Research, vol. 1, no. 1, p. 24, 2011.
Q. Zhu, Y. Wu, Y. Li et al., “Positive effects of hydrogen-water bathing in patients of psoriasis and parapsoriasis en plaques,” Scientific Reports, vol. 8, no. 1, pp. 8051–8051, 2018.
F. Xu, S. Yu, M. Qin et al., “Hydrogen-rich saline ameliorates allergic rhinitis by reversing the imbalance of Th1/Th2 and up-regulation of CD4+CD25+Foxp3+regulatory T cells, interleukin-10, and membrane-bound transforming growth factor-β in guinea pigs,” Inflammation, vol. 41, no. 1, pp. 81–92, 2018.
J. Akagi, “Immunological effect of hydrogen gas-hydrogen gas improves clinical outcomes of cancer patients,” Gan to Kagaku Ryoho, vol. 45, no. 10, pp. 1475–1478, 2018.View at: Google Scholar
Y. Terasaki, I. Ohsawa, M. Terasaki et al., “Hydrogen therapy attenuates irradiation-induced lung damage by reducing oxidative stress,” American Journal of Physiology Lung Cellular and Molecular Physiology, vol. 301, no. 4, pp. L415–L426, 2011.
L. Li, X. Li, Z. Zhang et al., “Effects of hydrogen-rich water on the PI3K/AKT signaling pathway in rats with myocardial ischemia-reperfusion injury,” Current Molecular Medicine, vol. 20, no. 5, pp. 396–406, 2020.
X. Li, L. Li, X. Liu et al., “Attenuation of cardiac ischaemia-reperfusion injury by treatment with hydrogen-rich water,” Current Molecular Medicine, vol. 19, no. 4, pp. 294–302, 2019.
Y. Zhang, Y. Liu, and J. Zhang, “Saturated hydrogen saline attenuates endotoxin-induced lung dysfunction,” The Journal of Surgical Research, vol. 198, no. 1, pp. 41–49, 2015.
D. Li and Y. Ai, “Hydrogen saline suppresses neuronal cell apoptosis and inhibits the p38 mitogen-activated protein kinase-caspase-3 signaling pathway following cerebral ischemia-reperfusion injury,” Molecular Medicine Reports, vol. 16, no. 4, pp. 5321–5325, 2017.
D. Wang, L. Wang, Y. Zhang, Y. Zhao, and G. Chen, “Hydrogen gas inhibits lung cancer progression through targeting SMC3,” Biomedicine & Pharmacotherapy, vol. 104, pp. 788–797, 2018.
Q. Li, Y. Tanaka, and N. Miwa, “Influence of hydrogen-occluding-silica on migration and apoptosis in human esophageal cells in vitro,” Medical Gas Research, vol. 7, no. 2, pp. 76–85, 2017.
X. Zhuang, Y. Yu, Y. Jiang et al., “Molecular hydrogen attenuates sepsis-induced neuroinflammation through regulation of microglia polarization through an mTOR-autophagy-dependent pathway,” International Immunopharmacology, vol. 81, article 106287, 2020.
P. Guan, Z. M. Sun, L. F. Luo et al., “Hydrogen protects against chronic intermittent hypoxia induced renal dysfunction by promoting autophagy and alleviating apoptosis,” Life Sciences, vol. 225, pp. 46–54, 2019.
J. Yuan, D. Wang, Y. Liu, X. Chen, and H. Zhang, “Effects of hydrogen rich water on the expression of Nrf 2 and the oxidative stress in rats with traumatic brain injury,” Zhonghua wei zhong bing ji jiu yi xue, vol. 27, no. 11, pp. 911–915, 2015.View at: Google Scholar
A. Pla, M. Pascual, J. Renau-Piqueras, and C. Guerri, “TLR4 mediates the impairment of ubiquitin-proteasome and autophagy-lysosome pathways induced by ethanol treatment in brain,” Cell Death & Disease, vol. 5, no. 2, article e1066, 2014.
S. M. Man, R. Karki, and T.-D. Kanneganti, “Molecular mechanisms and functions of pyroptosis, inflammatory caspases and inflammasomes in infectious diseases,” Immunological Reviews, vol. 277, no. 1, pp. 61–75, 2017.
M. Yan, Y. Yu, X. Mao et al., “Hydrogen gas inhalation attenuates sepsis-induced liver injury in a FUNDC1-dependent manner,” International Immunopharmacology, vol. 71, pp. 61–67, 2019.
S. Tan, Z. Long, X. Hou et al., “H2 protects against lipopolysaccharide-induced cardiac dysfunction via blocking TLR4-mediated cytokines expression,” Frontiers in Pharmacology, vol. 10, pp. 865–865, 2019.
Q. Pu, C. Gan, R. Li et al., “Atg7 deficiency intensifies inflammasome activation and pyroptosis in Pseudomonas Sepsis,” Journal of immunology, vol. 198, no. 8, pp. 3205–3213, 2017.
M. Deng, Y. Tang, W. Li et al., “The endotoxin delivery protein HMGB1 mediates caspase-11-dependent lethality in sepsis,” Immunity, vol. 49, no. 4, pp. 740–753.e7, 2018.
C. Li, L. Hou, D. Chen et al., “Hydrogen-rich saline attenuates isoflurane-induced caspase-3 activation and cognitive impairment via inhibition of isoflurane-induced oxidative stress, mitochondrial dysfunction, and reduction in ATP levels,” American Journal of Translational Research, vol. 9, no. 3, pp. 1162–1172, 2017.View at: Google Scholar
C. Y. Taabazuing, M. C. Okondo, and D. A. Bachovchin, “Pyroptosis and apoptosis pathways engage in bidirectional crosstalk in monocytes and macrophages,” Cell chemical biology, vol. 24, no. 4, pp. 507–514.e4, 2017.
S. J. Dixon, K. M. Lemberg, M. R. Lamprecht et al., “Ferroptosis: an iron-dependent form of nonapoptotic cell death,” Cell, vol. 149, no. 5, pp. 1060–1072, 2012.
Y. Li, F. Chen, J. Chen et al., “Disulfiram/copper induces antitumor activity against both nasopharyngeal cancer cells and cancer-associated fibroblasts through ROS/MAPK and ferroptosis pathways,” Cancers, vol. 12, no. 1, p. 138, 2020.
F. Ye, W. Chai, M. Xie et al., “HMGB1 regulates erastin-induced ferroptosis via RAS-JNK/p38 signaling in HL-60/NRASQ61L cells,” American Journal of Cancer Research, vol. 9, no. 4, pp. 730–739, 2019.View at: Google Scholar
O. Adedoyin, R. Boddu, A. Traylor et al., “Heme oxygenase-1 mitigates ferroptosis in renal proximal tubule cells,” Renal Physiology, vol. 314, no. 5, pp. F702–F714, 2018.
C. Li, X. Deng, X. Xie, Y. Liu, J. P. Friedmann Angeli, and L. Lai, “Activation of glutathione peroxidase 4 as a novel anti-inflammatory strategy,” Frontiers in Pharmacology, vol. 9, pp. 1120–1120, 2018.
F. A.-O. X. Rijo-Ferreira and J. S. Takahashi, “Genomics of circadian rhythms in health and disease,” Genome Medicine, vol. 11, no. 1, p. 82, 2019.
C. A. Thaiss, M. Levy, T. Korem et al., “Microbiota diurnal rhythmicity programs host transcriptome oscillations,” Cell, vol. 167, no. 6, pp. 1495–1510.e12, 2016.
A. Iida, N. Nosaka, T. Yumoto et al., “The clinical application of hydrogen as a medical treatment,” Acta Medica Okayama, vol. 70, no. 5, pp. 331–337, 2016.
M. Wilking, M. Ndiaye, H. Mukhtar, and N. Ahmad, “Circadian rhythm connections to oxidative stress: implications for human health,” Antioxidants & Redox Signaling, vol. 19, no. 2, pp. 192–208, 2013.
G. Russell, M. Rehman, L. B. TW, D. Veal, E. Adukwu, and J. Hancock, “An overview of SARS-CoV-2 (COVID-19) infection and the importance of molecular hydrogen as an adjunctive therapy,” Reactive Oxygen Species, https://uwe-repository.worktribe.com/output/6050001.View at: Google Scholar
W.-J. Guan, C. H. Wei, A. L. Chen et al., “Hydrogen/oxygen mixed gas inhalation improves disease severity and dyspnea in patients with Coronavirus disease 2019 in a recent multicenter, open-label clinical trial,” Journal of Thoracic Disease, vol. 12, no. 6, pp. 3448–3452, 2020.
F. Zhou, T. Yu, R. du et al., “Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study,” The Lancet, vol. 395, no. 10229, pp. 1054–1062, 2020.
C. Huang, Y. Wang, X. Li et al., “Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China,” The Lancet, vol. 395, no. 10223, pp. 497–506, 2020.
L. Gattinoni, T. Tonetti, and M. Quintel, “Regional physiology of ARDS,” Critical Care, vol. 21, Supplement 3, p. 312, 2017.
W. W. Dong, Y. Q. Zhang, X. Y. Zhu et al., “Protective effects of hydrogen-rich saline against lipopolysaccharide-induced alveolar epithelial-to-mesenchymal transition and pulmonary fibrosis,” Medical Science Monitor, vol. 23, pp. 2357–2364, 2017.
T. Wang, L. Zhao, M. Liu et al., “Oral intake of hydrogen-rich water ameliorated chlorpyrifos-induced neurotoxicity in rats,” Toxicology and Applied Pharmacology, vol. 280, no. 1, pp. 169–176, 2014.
Y. Liu and J. Zhang, “Saturated hydrogen saline ameliorates lipopolysaccharide-induced acute lung injury by reducing excessive autophagy,” Experimental and Therapeutic Medicine, vol. 13, no. 6, pp. 2609–2615, 2017.
X. Chen, Q. Liu, D. Wang et al., “Protective effects of hydrogen-rich saline on rats with smoke inhalation injury,” Oxidative Medicine and Cellular Longevity, vol. 2015, Article ID 106836, 8 pages, 2015.
D. H. Moon, D. Y. Kang, S. J. Haam et al., “Hydrogen gas inhalation ameliorates lung injury after hemorrhagic shock and resuscitation,” Journal of Thoracic Disease, vol. 11, no. 4, pp. 1519–1527, 2019.
Z. Liu, W. Geng, C. Jiang et al., “Hydrogen-rich saline inhibits tobacco smoke-induced chronic obstructive pulmonary disease by alleviating airway inflammation and mucus hypersecretion in rats,” Experimental Biology and Medicine, vol. 242, no. 15, pp. 1534–1541, 2017.
Y. Fu, M. Ito, Y. Fujita et al., “Molecular hydrogen is protective against 6-hydroxydopamine-induced nigrostriatal degeneration in a rat model of Parkinson’s disease,” Neuroscience Letters, vol. 453, no. 2, pp. 81–85, 2009.
K. Fujita, T. Seike, N. Yutsudo 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, vol. 4, no. 9, p. e7247, 2009.
K. Nishimaki, T. Asada, I. Ohsawa et al., “Effects of molecular hydrogen assessed by an animal model and a randomized clinical study on mild cognitive impairment,” Current Alzheimer Research, vol. 15, no. 5, pp. 482–492, 2018.
H. Chen, J. Guo, C. Wang et al., “Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records,” The Lancet, vol. 395, no. 10226, pp. 809–815, 2020.
H. Zhu, L. Wang, C. Fang et al., “Clinical analysis of 10 neonates born to mothers with 2019-nCoV pneumonia,” Translational Pediatrics, vol. 9, no. 1, pp. 51–60, 2020.
K. Imai, T. Kotani, H. Tsuda et al., “Administration of molecular hydrogen during pregnancy improves behavioral abnormalities of offspring in a maternal immune activation model,” Scientific Reports, vol. 8, no. 1, article 9221, 2018.
J. Nemeth, V. Toth-Szuki, V. Varga, V. Kovacs, G. Remzso, and F. Domoki, “Molecular hydrogen affords neuroprotection in a translational piglet model of hypoxic-ischemic encephalopathy,” Journal of Physiology and Pharmacology, vol. 67, no. 5, pp. 677–689, 2016.View at: Google Scholar
Y. Mano, T. Kotani, M. Ito et al., “Maternal molecular hydrogen administration ameliorates rat fetal hippocampal damage caused by in utero ischemia–reperfusion,” Free Radical Biology and Medicine, vol. 69, pp. 324–330, 2014.
H. Ono, Y. Nishijima, S. Ohta et al., “Hydrogen gas inhalation treatment in acute cerebral infarction: a randomized controlled clinical study on safety and neuroprotection,” Journal of Stroke and Cerebrovascular Diseases, vol. 26, no. 11, pp. 2587–2594, 2017.
R. Camara, N. Matei, J. Camara, B. Enkhjargal, J. Tang, and J. H. Zhang, “Hydrogen gas therapy improves survival rate and neurological deficits in subarachnoid hemorrhage rats: a pilot study,” Medical Gas Research, vol. 9, no. 2, pp. 74–79, 2019.
K. Zhuang, Y. C. Zuo, P. Sherchan, J. K. Wang, X. X. Yan, and F. Liu, “Hydrogen inhalation attenuates oxidative stress related endothelial cells injury after subarachnoid hemorrhage in rats,” Frontiers in Neuroscience, vol. 13, article 1441, 2020.
H. Chen, C. Zhou, K. Xie, X. Meng, Y. Wang, and Y. Yu, “Hydrogen-rich saline alleviated the hyperpathia and microglia activation via autophagy mediated inflammasome inactivation in neuropathic pain rats,” Neuroscience, vol. 421, pp. 17–30, 2019.
L. Y. Ma, W. W. Chen, R. L. Gao et al., “China cardiovascular diseases report 2018: an updated summary,” Journal of Geriatric Cardiology, vol. 17, no. 1, pp. 1–8, 2020.
I. Ohsawa, K. Nishimaki, K. Yamagata, M. Ishikawa, and S. Ohta, “Consumption of hydrogen water prevents atherosclerosis in apolipoprotein E knockout mice,” Biochemical and Biophysical Research Communications, vol. 377, no. 4, pp. 1195–1198, 2008.
M. Iketani, K. Sekimoto, T. Igarashi et al., “Administration of hydrogen-rich water prevents vascular aging of the aorta in LDL receptor-deficient mice,” Scientific Reports, vol. 8, no. 1, article 16822, 2018.
T. Sakai, B. Sato, K. Hara et al., “Consumption of water containing over 3.5 mg of dissolved hydrogen could improve vascular endothelial function,” Vascular Health and Risk Management, vol. 10, pp. 591–597, 2014.
J. Ding, Z. Yang, H. Ma, and H. Zhang, “Mitochondrial aldehyde dehydrogenase in myocardial ischemic and ischemia-reperfusion injury,” in Aldehyde Dehydrogenases, J. Ren, Y. Zhang, and J. Ge, Eds., vol. 1193 of Advances in Experimental Medicine and Biology, Springer, Singapore.
L. Li, T. Liu, L. Liu et al., “Effect of hydrogen-rich water on the Nrf2/ARE signaling pathway in rats with myocardial ischemia-reperfusion injury,” Journal of Bioenergetics and Biomembranes, vol. 51, no. 6, pp. 393–402, 2019.
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,” International Journal of Cardiology, vol. 48, no. 1, pp. 91–95, 2011.
Q. Sun, Z. Kang, J. Cai et al., “Hydrogen-rich saline protects myocardium against ischemia/reperfusion injury in rats,” Experimental Biology and Medicine, vol. 234, no. 10, pp. 1212–1219, 2009.
L. Qian, F. Cao, J. Cui et al., “The potential cardioprotective effects of hydrogen in irradiated mice,” Journal of Radiation Research, vol. 51, no. 6, pp. 741–747, 2010.
H. Zheng and Y. S. Yu, “Chronic hydrogen-rich saline treatment attenuates vascular dysfunction in spontaneous hypertensive rats,” Biochemical Pharmacology, vol. 83, no. 9, pp. 1269–1277, 2012.
Y. Wang, L. Jing, X. M. Zhao et al., “Protective effects of hydrogen-rich saline on monocrotaline-induced pulmonary hypertension in a rat model,” Respiratory Research, vol. 12, no. 1, 2011.
K. Hayashida, M. Sano, N. Kamimura et al., “H2Gas improves functional outcome after cardiac arrest to an extent comparable to therapeutic hypothermia in a rat model,” Journal of the American Heart Association, vol. 1, no. 5, article e003459, 2012.
Y. Ding, H. Wang, H. Shen et al., “The clinical pathology of severe acute respiratory syndrome (SARS): a report from China,” The Journal of Pathology, vol. 200, no. 3, pp. 282–289, 2003.
A. Badawi and S. G. Ryoo, “Prevalence of comorbidities in the Middle East respiratory syndrome coronavirus (MERS-CoV): a systematic review and meta-analysis,” International Journal of Infectious Diseases, vol. 49, pp. 129–133, 2016.
K. J. Clerkin, J. A. Fried, J. Raikhelkar et al., “COVID-19 and Cardiovascular Disease,” Circulation, vol. 141, no. 20, pp. 1648–1655, 2020.
E. Driggin, M. V. Madhavan, B. Bikdeli et al., “Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the COVID-19 Pandemic,” Journal of the American College of Cardiology, vol. 75, no. 18, pp. 2352–2371, 2020.
B. Li, J. Yang, F. Zhao et al., “Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China,” Clinical Research in Cardiology, vol. 109, no. 5, pp. 531–538, 2020.
S. Li, M. Fujino, N. Ichimaru et al., “Molecular hydrogen protects against ischemia-reperfusion injury in a mouse fatty liver model via regulating HO-1 and Sirt1 expression,” Scientific Reports, vol. 8, no. 1, article 14019, 2018.
H. Li, O. Chen, Z. Ye et al., “Inhalation of high concentrations of hydrogen ameliorates liver ischemia/reperfusion injury through A 2A receptor mediated PI3K-Akt pathway,” Biochemical Pharmacology, vol. 130, no. 83, pp. 83–92, 2017.
Q. Zhang, C. Piao, J. Xu et al., “Comparative study on protective effect of hydrogen rich saline and adipose- derived stem cells on hepatic ischemia-reperfusion and hepatectomy injury in swine,” Biomedicine & Pharmacotherapy, vol. 120, article 109453, 2019.
Q. Zhang, Y. Ge, H. Li et al., “Corrigendum to “Effect of hydrogen-rich saline on apoptosis induced by hepatic ischemia reperfusion upon laparoscopic hepatectomy in miniature pigs” [Research in Veterinary Science, Volume 119, August 2018, Pages 285–291],” Research in Veterinary Science, vol. 126, p. 37, 2019.
G. Bai, H. Li, Y. Ge et al., “Influence of hydrogen-rich saline on hepatocyte autophagy during laparoscopic liver ischaemia-reperfusion combined resection injury in miniature pigs,” Journal of Veterinary Research, vol. 62, no. 3, pp. 395–403, 2018.
H. Li, G. Bai, Y. Ge et al., “Hydrogen-rich saline protects against small-scale liver ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress,” Life Sciences, vol. 194, pp. 7–14, 2018.
I. Tamaki, K. Hata, Y. Okamura et al., “Hydrogen flush after cold storage as a new end-ischemic ex vivo treatment for liver grafts against ischemia/reperfusion injury,” Liver Transplantation, vol. 24, no. 11, pp. 1589–1602, 2018.
B. Gharib, S. Hanna, O. M. S. Abdallahi, H. Lepidi, B. Gardette, and M. de Reggi, “Anti-inflammatory properties of molecular hydrogen: investigation on parasite- induced liver inflammation,” Comptes Rendus de l’Académie des Sciences – Series III – Sciences de la Vie, vol. 324, no. 8, pp. 719–724, 2001.
Q. Liu, W. F. Shen, H. Y. Sun et al., “Hydrogen-rich saline protects against liver injury in rats with obstructive jaundice,” Liver International, vol. 30, no. 7, pp. 958–968, 2010.
Y. Dang, T. Liu, X. Mei et al., “Hyperoxygenated hydrogen–rich solution suppresses shock- and resuscitation- induced liver injury,” Journal of Surgical Research, vol. 220, pp. 363–371, 2017.
M. Iketani, J. Ohshiro, T. Urushibara et al., “Preadministration of hydrogen-rich water protects against lipopolysaccharide-induced sepsis and attenuates liver injury,” Shock, vol. 48, no. 1, pp. 85–93, 2017.
H. L. Hu, J. Gao, W. J. Guo, F. H. Zhou, H. Y. Liu, and C. C. Su, “Anti-injury effect of hydrogen-enriched water in a rat model of liver injury induced by aflatoxin B1,” Acta Physiologica Sinica, vol. 71, no. 5, pp. 725–731, 2019.View at: Google Scholar
X. Wang and J. Wang, “High-content hydrogen water-induced downregulation of miR-136 alleviates non-alcoholic fatty liver disease by regulating Nrf2 via targeting MEG3,” Biological Chemistry, vol. 399, no. 4, pp. 397–406, 2018.
D. Korovljev, V. Stajer, J. Ostojic, T. W. LeBaron, and S. M. Ostojic, “Hydrogen-rich water reduces liver fat accumulation and improves liver enzyme profiles in patients with non-alcoholic fatty liver disease: a randomized controlled pilot trial,” Clinics and Research in Hepatology and Gastroenterology, vol. 43, no. 6, pp. 688–693, 2019.
C. Xia, W. Liu, D. Zeng, L. Zhu, X. Sun, and X. Sun, “Effect of hydrogen-rich water on oxidative stress, liver function, and viral load in patients with chronic hepatitis B,” Clinical and Translational Science, vol. 6, no. 5, pp. 372–375, 2013.
T. Li and J. Y. L. Chiang, “Bile acid signaling in metabolic disease and drug therapy,” Pharmacological Reviews, vol. 66, no. 4, pp. 948–983, 2014.
S. C. Harris, S. Devendran, C. Méndez-García et al., “Bile acid oxidation by Eggerthella lenta strains C592 and DSM 2243T,” Gut Microbes, vol. 9, no. 6, pp. 523–539, 2018.
K. Katada, T. Takagi, K. Uchiyama, and Y. Naito, “Therapeutic roles of carbon monoxide in intestinal ischemia-reperfusion injury,” Journal of Gastroenterology and Hepatology, vol. 30, pp. 46–52, 2015.
W. Yao, X. Lin, X. Han et al., “MicroRNA files in the prevention of intestinal ischemia/reperfusion injury by hydrogen rich saline,” Bioscience Reports, vol. 40, no. 1, 2020.
H. Chen, Y. P. Sun, P. F. Hu et al., “The effects of hydrogen-rich saline on the contractile and structural changes of intestine induced by ischemia-reperfusion in rats,” Journal of Surgical Research, vol. 167, no. 2, pp. 316–322, 2011.
T. Shigeta, S. Sakamoto, X. K. Li et al., “Luminal injection of hydrogen-rich solution attenuates intestinal ischemia-reperfusion injury in rats,” Transplantation, vol. 99, no. 3, pp. 500–507, 2015.
S. Eryilmaz, Z. Turkyilmaz, R. Karabulut et al., “The effects of hydrogen-rich saline solution on intestinal anastomosis performed after intestinal ischemia reperfusion injury,” Journal of Pediatric Surgery, 2020.
Y. Higashimura, Y. Baba, R. Inoue et al., “Effects of molecular hydrogen-dissolved alkaline electrolyzed water on intestinal environment in mice,” Medical Gas Research, vol. 8, no. 1, pp. 6–11, 2018.
M. Ikeda, K. Shimizu, H. Ogura et al., “Hydrogen-rich saline regulates intestinal barrier dysfunction, dysbiosis, and bacterial translocation in a murine model of sepsis,” Shock, vol. 50, no. 6, pp. 640–647, 2018.
Y. Yu, Y. Yang, Y. Bian 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, vol. 48, no. 3, pp. 364–370, 2017.
J. Akagi and H. Baba, “Hydrogen gas restores exhausted CD8+ T cells in patients with advanced colorectal cancer to improve prognosis,” Oncology Reports, vol. 41, no. 1, pp. 301–311, 2019.
G. Wang, J. Romero-Gallo, S. L. Benoit et al., “Hydrogen metabolism inHelicobacter pyloriPlays a role in gastric carcinogenesis through facilitating CagA translocation,” mBio, vol. 7, no. 4, 2016.
X. Liu, Z. Chen, N. Mao, and Y. Xie, “The protective of hydrogen on stress-induced gastric ulceration,” International Immunopharmacology, vol. 13, no. 2, pp. 197–203, 2012.
J.-Y. Zhang, Q. F. Wu, Y. Wan et al., “Protective role of hydrogen-rich water on aspirin-induced gastric mucosal damage in rats,” World Journal of Gastroenterology, vol. 20, no. 6, pp. 1614–1622, 2014.
S. Franceschelli, D. M. P. Gatta, M. Pesce et al., “Modulation of the oxidative plasmatic state in gastroesophageal reflux disease with the addition of rich water molecular hydrogen: a new biological vision,” Journal of Cellular and Molecular Medicine, vol. 22, no. 5, pp. 2750–2759, 2018.
Q. Shi, C. Chen, W. H. Deng et al., “Hydrogen-rich saline attenuates acute hepatic injury in acute necrotizing pancreatitis by inhibiting inflammation and apoptosis, involving JNK and p38 mitogen-activated protein kinase–dependent reactive oxygen species,” Pancreas, vol. 45, no. 10, pp. 1424–1431, 2016.
Y. Yang, P. Y. Liu, W. Bao, S. J. Chen, F. S. Wu, and P. Y. Zhu, “Hydrogen inhibits endometrial cancer growth via a ROS/NLRP3/caspase-1/GSDMD-mediated pyroptotic pathway,” BMC Cancer, vol. 20, no. 1, p. 28, 2020.
Y. He, J. Z. Shi, R. J. Zhang et al., “Effects of hydrogen gas inhalation on endometriosis in rats,” Reproductive Sciences, vol. 24, no. 2, pp. 324–331, 2016.
N. Gokalp, A. C. Basaklar, K. Sonmez et al., “Protective effect of hydrogen rich saline solution on experimental ovarian ischemia reperfusion model in rats,” Journal of Pediatric Surgery, vol. 52, no. 3, pp. 492–497, 2017.
X. Meng, H. Chen, G. Wang, Y. Yu, and K. Xie, “Hydrogen-rich saline attenuates chemotherapy-induced ovarian injury via regulation of oxidative stress,” Experimental and Therapeutic Medicine, vol. 10, no. 6, pp. 2277–2282, 2015.
X. He, S. Y. Wang, C. H. Yin, T. Wang, C. W. Jia, and Y. M. Ma, “Hydrogen-rich water exerting a protective effect on ovarian reserve function in a mouse model of immune premature ovarian failure induced by zona pellucida 3,” Chinese Medical Journal, vol. 129, no. 19, pp. 2331–2337, 2016.
L. Ge, L. H. Wei, C. Q. du et al., “Hydrogen-rich saline attenuates spinal cord hemisection-induced testicular injury in rats,” Oncotarget, vol. 8, no. 26, pp. 42314–42331, 2017.
Z. Jiang, B. Xu, M. Yang, Z. Li, Y. Zhang, and D. Jiang, “Protection by hydrogen against gamma ray-induced testicular damage in rats,” Basic & Clinical Pharmacology & Toxicology, vol. 112, no. 3, pp. 186–191, 2013.
J. Y. Ku, M. J. Park, H. J. Park, N. C. Park, and B. S. Joo, “Combination of Korean red ginseng extract and hydrogen-rich water improves spermatogenesis and sperm motility in male mice,” Chinese Journal of Integrative Medicine, vol. 26, no. 5, pp. 361–369, 2020.
R. Begum, J. Bajgai, A. Fadriquela, C. S. Kim, S. K. Kim, and K. J. Lee, “Molecular hydrogen may enhance the production of testosterone hormone in male infertility through hormone signal modulation and redox balance,” Medical Hypotheses, vol. 121, pp. 6–9, 2018.
J. Guo, D. Zhao, X. Lei et al., “Protective effects of hydrogen against low-dose long-term radiation-induced damage to the behavioral performances, hematopoietic system, genital system, and splenic lymphocytes in mice,” Oxidative Medicine and Cellular Longevity, vol. 2016, Article ID 1947819, 15 pages, 2016.
S. Wu, Z. Fang, and S. Zhou, “Saturated hydrogen alleviates CCl4-induced acute kidney injury via JAK2/STAT3/p65 signaling,” The Journal of International Medical Research, vol. 48, no. 1, 2020.
W. Yao, A. Guo, X. Han et al., “Aerosol inhalation of a hydrogen-rich solution restored septic renal function,” Aging, vol. 11, no. 24, pp. 12097–12113, 2019.
J. Chen, H. Zhang, J. Hu et al., “Hydrogen-rich saline alleviates kidney fibrosis following AKI and retains klotho expression,” Frontiers in Pharmacology, vol. 8, p. 499, 2017.
H. Du, M. Sheng, L. Wu et al., “Hydrogen-rich saline attenuates acute kidney injury after liver transplantation via activating p53-mediated autophagy,” Transplantation, vol. 100, no. 3, pp. 563–570, 2016.
S. X. Guo, Q. Fang, C. G. You et al., “Effects of hydrogen-rich saline on early acute kidney injury in severely burned rats by suppressing oxidative stress induced apoptosis and inflammation,” Journal of Translational Medicine, vol. 13, no. 1, p. 183, 2015.
Q. Shi, K. S. Liao, K. L. Zhao et al., “Hydrogen-Rich Saline Attenuates Acute Renal Injury in Sodium Taurocholate- Induced Severe Acute Pancreatitis by Inhibiting ROS and NF-κB Pathway,” Mediators of Inflammation, vol. 2015, Article ID 685043, 13 pages, 2015.
Y. Lu, C.‒. F. Li, N.‒. N. Ping et al., “Hydrogen-rich water alleviates cyclosporine A-induced nephrotoxicity via the Keap1/Nrf2 signaling pathway,” Journal of Biochemical and Molecular Toxicology, vol. 34, no. 5, article e22467, 2020.
Z. Xing, W. Pan, J. Zhang et al., “Hydrogen rich water attenuates renal injury and fibrosis by regulation transforming growth factor-β induced Sirt1,” Biological & Pharmaceutical Bulletin, vol. 40, no. 5, pp. 610–615, 2017.
J. Li, Z. Hong, H. Liu et al., “Hydrogen-rich saline promotes the recovery of renal function after ischemia/reperfusion injury in rats via anti-apoptosis and anti-inflammation,” Frontiers in Pharmacology, vol. 7, p. 106, 2016.
N. Miyazaki, O. Yamaguchi, M. Nomiya, K. Aikawa, and J. Kimura, “Preventive effect of hydrogen water on the development of detrusor overactivity in a rat model of bladder outlet obstruction,” The Journal of Urology, vol. 195, no. 3, pp. 780–787, 2016.
X. Qiu, Q. Ye, M. Sun, L. Wang, Y. Tan, and G. Wu, “Saturated hydrogen improves lipid metabolism disorders and dysbacteriosis induced by a high-fat diet,” Experimental Biology and Medicine, vol. 245, no. 6, pp. 512–521, 2020.
X. Zhang, J. Liu, K. Jin et al., “Subcutaneous injection of hydrogen gas is a novel effective treatment for type 2 diabetes,” Journal of Diabetes Investigation, vol. 9, no. 1, pp. 83–90, 2018.
L. Zhao, Y. Wang, G. Zhang, T. Zhang, J. Lou, and J. Liu, “L-Arabinose elicits gut-derived hydrogen production and ameliorates metabolic syndrome in C57BL/6J mice on high-fat-diet,” Nutrients, vol. 11, no. 12, p. 3054, 2019.
A. Tamasawa, K. Mochizuki, N. Hariya et al., “Hydrogen gas production is associated with reduced interleukin-1β mRNA in peripheral blood after a single dose of acarbose in Japanese type 2 diabetic patients,” European Journal of Pharmacology, vol. 762, pp. 96–101, 2015.
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, vol. 19, no. 7, pp. 1396–1403, 2011.
Y. Niu, Q. Nie, L. Dong et al., “Hydrogen attenuates allergic inflammation by reversing energy metabolic pathway switch,” Scientific Reports, vol. 10, no. 1, article 1962, 2020.
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,” Medical Gas Research, vol. 2, no. 1, p. 12, 2012.
M. Yamazaki, K. Kusano, T. Ishibashi, M. Kiuchi, and K. Koyama, “Intravenous infusion of H2-saline suppresses oxidative stress and elevates antioxidant potential in thoroughbred horses after racing exercise,” Scientific Reports, vol. 5, no. 1, article 15514, 2015.
T. Kawamura, K. Suzuki, M. Takahashi et al., “Involvement of neutrophil dynamics and function in exercise-induced muscle damage and delayed-onset muscle soreness: effect of hydrogen bath,” Antioxidants, vol. 7, no. 10, p. 127, 2018.
M. Watanabe, N. Kamimura, K. Iuchi et al., “Protective effect of hydrogen gas inhalation on muscular damage using a mouse hindlimb ischemia-reperfusion injury model,” Plastic and Reconstructive Surgery, vol. 140, no. 6, pp. 1195–1206, 2017.
S. Hasegawa, M. Ito, M. Fukami, M. Hashimoto, M. Hirayama, and K. Ohno, “Molecular hydrogen alleviates motor deficits and muscle degeneration in mdx mice,” Redox Report, vol. 22, no. 1, pp. 26–34, 2016.
S. Watanabe, M. Fujita, M. Ishihara et al., “Protective effect of inhalation of hydrogen gas on radiation-induced dermatitis and skin injury in rats,” Journal of Radiation Research, vol. 55, no. 6, pp. 1107–1113, 2014.
W. Fang, G. Wang, L. Tang et al., “Hydrogen gas inhalation protects against cutaneous ischaemia/reperfusion injury in a mouse model of pressure ulcer,” Journal of Cellular and Molecular Medicine, vol. 22, no. 9, pp. 4243–4252, 2018.
T. Ishibashi, M. Ichikawa, B. Sato et al., “Improvement of psoriasis-associated arthritis and skin lesions by treatment with molecular hydrogen: a report of three cases,” Molecular Medicine Reports, vol. 12, no. 2, pp. 2757–2764, 2015.
T. Kurioka, T. Matsunobu, Y. Satoh, K. Niwa, and A. Shiotani, “Inhaled hydrogen gas therapy for prevention of noise-induced hearing loss through reducing reactive oxygen species,” Neuroscience Research, vol. 89, pp. 69–74, 2014.
C. Cejka, J. Kossl, B. Hermankova, V. Holan, and J. Cejkova, “Molecular hydrogen effectively heals alkali-injured cornea via suppression of oxidative stress,” Oxidative Medicine and Cellular Longevity, vol. 2017, Article ID 8906027, 12 pages, 2017.
J. G. Lehman, R. D. Causey, C. V. LaGrasta, and A. L. Ruff, “High throughput siRNA screening for chloropicrin and hydrogen fluoride-induced cornea epithelial cell injury,” Journal of Visualized Experiments, no. 136, 2018.
C. Cejka, J. Kossl, B. Hermankova et al., “Therapeutic effect of molecular hydrogen in corneal UVB-induced oxidative stress and corneal photodamage,” Scientific Reports, vol. 7, no. 1, article 18017, 2017.
M. Y. Liu, F. Xie, Y. Zhang et al., “Molecular hydrogen suppresses glioblastoma growth via inducing the glioma stem-like cell differentiation,” Stem Cell Research & Therapy, vol. 10, no. 1, p. 145, 2019.
Y. Jiang, G. Liu, L. Zhang et al., “Therapeutic efficacy of hydrogen-rich saline alone and in combination with PI3K inhibitor in non-small cell lung cancer,” Molecular Medicine Reports, vol. 18, no. 2, pp. 2182–2190, 2018.
J. Chen, F. Mu, T. Lu, Y. Ma, D. du, and K. Xu, “A gallbladder carcinoma patient with pseudo-progressive remission after hydrogen inhalation,” OncoTargets and Therapy, vol. 12, pp. 8645–8651, 2019.
J. Chen, F. Mu, T. Lu, D. du, and K. Xu, “Brain metastases completely disappear in non-small cell lung cancer using hydrogen gas inhalation: a case report,” OncoTargets and Therapy, vol. 12, pp. 11145–11151, 2019.
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 Chemotherapy and Pharmacology, vol. 64, no. 4, pp. 753–761, 2009.
K. Mei, S. Zhao, L. Qian, B. Li, J. Ni, and J. Cai, “Hydrogen protects rats from dermatitis caused by local radiation,” The Journal of Dermatological Treatment, vol. 25, no. 2, pp. 182–188, 2013.
Z. Xu, L. Shi, Y. Wang et al., “Pathological findings of COVID-19 associated with acute respiratory distress syndrome,” The Lancet Respiratory Medicine
W. J. Guan, R. C. Chen, and N. S. Zhong, “Strategies for the prevention and management of coronavirus disease 2019,” European Respiratory