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Molecular hydrogen: a therapeutic antioxidant and beyond

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Molecular hydrogen: a therapeutic antioxidant and beyond ( molecular-hydrogen-therapeutic-antioxidant-and-beyond )

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in Nature Medicine, research on the molecular hydrogen medicine has blossomed worldwide. Emerging evidence has demonstrated the pleiotropic therapeutic effects of molecular hydrogen in a variety of animal disease mod- els and some human patients (Huang et al., 2010; Ohta, 2011; Dixon et al., 2013; Ishibashi et al., 2015; Kurokawa et al., 2015), which are comparable to what have been found with other traditional therapeutic gases regimens including hyperbaric/normobaric oxygen (Harch, 2015; Hu et al., 2015; Parra et al., 2015; Stoller, 2015; Weaver and Liu, 2015; Yan et al., 2015) and hyrogen sulfide (H2S) (Herrera et al., 2015; Langston and Toombs, 2015). H2 is now considered as a signaling gaseous molecule with physiological functions similar to that of nitric oxide (NO), carbon monoxide (CO), and H2S (Kajimura et al., 2012). Indeed, H2 has no cytotoxicity even at high con- centration, which ensures the safety privilege compared to the other gases (Ohta, 2011). adMInIstratIon and bIologIcal benefIt of Molecular hydrogen Three adminstration forms of molecular hydrogen, namely 1–4% hydrogen gas inhalation, hydrogen-rich saline intraperitoneal injection/intravenous infusion and oral intake of hydrogen-saturated water, have been com- monly used in hydrogen medical research (Kurokawa et al., 2015; Wang et al., 2015). H2 concentrations in the tissues depend on the administered H2 concentration and specific tissue H2 uptake is related to the difference in administration route, indicating the importance to choos- ing most efficient delivery route and hydrogen dose for each disease or tissue (Liu et al., 2014). The therapeutic effect of molecular hydrogen H2 has been demonstrated in the central nervous system, cardiovascular system, lung, kidney, liver, pancreas, skin, eye, bone and repro- duction system which have the underlying pathological conditions of ischemia-reperfusion injury (including organ transplantation) and the predominant oxidative stress-mediated diseases (Huang et al., 2010; Ohta, 2011, 2015; Ichihara et al., 2015; Nakata et al., 2015; Iketani and Ohsawa, 2016). In a comprehensive review in 2015, Ichihara et al. have nicely summarized the biological benefit of molecular hydrogen in all organs covering 31 disease categories that can be subdivided into 166 disease models, human diseases, treatment-associated pathologies, and pathophysiological conditions of plants (Ichihara et al., 2015). Although the underlying mecha- nisms were initially proposed as selective extinctions of hydroxyl radical and peroxynitrite, the signaling pathway regulation effect of molecular hydrogen by modulating a various molecules expressions/activities, gene expres- sion and microRNA may also account for the ultimate effects of anti-reperfusion injury, anti-infammation, anti-apoptosis, anti-metabolic disorders, anti-allergy, anti-radiation injury, anti-dementia as well as anti-aging (Ichihara et al., 2015; Hara et al., 2016; Li et al., 2016; Shao et al., 2016). clInIcal applIcatIons of Molecular hydrogen Up to date, the clincal applications of molecular hydrogen to human patients has been conducted. The small cohert patients studies or case reports revealed the safety or some promising benefits of theraputic hydrogen in the a variety range of diseases and pathological status such as post-cardi- ac syndrome, Parkinson’s disease, acute cerebral ischemia, metabolic syndrome, rheumatoid arthritis, hemodylisis and postpsoriasis (Ichihara et al., 2015; Nakata et al., 2015; Tamura et al., 2016). More large-scale prospective clinical studies on Parkinson’s disease, acute post-cardiac arrest syndrome and myocardial infarction as well as cerebral infarction are currently ongiong (Ichihara et al., 2015). conclusIon Overall, the impact of molecular hydrogen in medicine is extraordinary. The non-toxic and rapid intracelluar diffusion features of this biological gas ensure the fea- sibility and readiness for its clinical translation. Future preclinical stuides are warranted to further elucidate the upstream master regulator(s) that drive molecular hydorgen-induced modifications of downstream effectors. It is also of importance to clarify the best adminstration modality and the optimal hydrogen dose regimen for each disease model preclinically and subsquently in sepcific patient population. A newly developed hydrogen-oxygen nebulizer machine (AMS-H-01, Asclepius Meditec Co., Ltd., Shanghai, China) is able to produce 66% hydrogen gas without the risk of spontaneous combustion. Given a dose-dependent benefit of hydrogen observed in the previous preclinical studies (Ohta, 2011; Ichihara et al., 2015), the therapeutic efficacy of such high hydrogen concentration deserves full investigation. Moreover, the well-designed multi-center clinical trials are expected to provide more solid evidences regarding to the effects of hydrogen in human patients. Huang L. / Med Gas Res www.medgasres.com 220 Med Gas Res ¦ December ¦ Volume 6 ¦ Issue 4 Author contributions LH conceived and wrote the manuscript as well as gath- ered the references. The author read and approved the final manuscript.

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