Molecular hydrogen: a therapeutic antioxidant and beyond

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REVIEW Molecular hydrogen: a therapeutic antioxidant and beyond Lei Huang1, 2, * 1 Department of Anesthesiology, Loma Linda University, Loma Linda, CA, USA 2 Department of Basic Sciences, Division of Physiology, Loma Linda University, Loma Linda, CA, USA *Correspondence to: Lei Huang, M.D., orcid: 0000-0002-7211-8337 Molecular hydrogen (H2) medicine research has flourished since a landmark publication in Nature Medicine that revealed the antioxidant and cytoprotective effects of hydrogen gas in a focal stroke model. Emerging evidence has consistently demonstrated that molecular hydrogen is a promising therapeutic option for a variety of diseases and the underlying comprehensive mechanisms is beyond pure hydroxyl radicals scavenging. The non-toxicity at high concentrations and rapid cellular diffusion features of molecular hydrogen ensure the feasibility and readiness of its clinical translation to human patients. Key words: hydrogen-saturated water/saline; hydrogen gas; free radical scavenger; anti-inflammation; anti-apoptosis; biological effect; clinical application; hydrogen-oxygen nebulizer machine doi: 10.4103/2045-9912.196904 How to cite this article: Huang L (2016) Molecular hydrogen: a therapeutic antioxidant and beyond. Med Gas Res 6(4):219-222. Open access statement: This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial- ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. Abstract IntroductIon Molecular hydrogen (H2), the most lightweight gas, is routinely used as a component of exotic breathing gas mixture, namely hydreliox (49% H2, 50% helium and 1% O2) for deep water divers to prevent decompression sickness (Abraini et al., 1994; Ohta, 2011). Therapeutic application of H2 as a free radical catalyzer debuted in 1970s. A 2-week treatment of hyperbaric 97.5% H2 gas in the absence of explosion risk caused a significant regression of skin tumor or leukemia in animals (Dole et al., 1975; Roberts et al., 1978). It was pospulated that the underlying mechansim was through hydroxyl radicals scanverging by exthermic reaction of H2 + ·OH = H2O + H· followed by H· + O2– = HO2– reaction (Dole et al., 1975). In 2001, Gharib et al. (2001) confirmed the similar treatment efficacy of hyperbaric hydrogen aganist parasite-induced mice liver inflammation, consistently suggesting the protective mechanism at least in part by the reaction of molecular hydrogen with hydroxyl radicals. Five years later, Ohsawa et al. (2007) intensively eluic- dated the seletive antioxidant feature of normobaric 2% H2 gas (below the 4% explosion level) and its cytoprotec- tive benefit against reperfusion oxidative injury using cell culture in vitro and a rat model of focal stroke in vivo. The finding added hydrogen as an innovative approach into a collection of therapeutic strategies against stroke (Dock et al., 2015; Li et al., 2015; Lioutas et al., 2015; Merali et al., 2015; Pena and Borlongan, 2015; Ploughman et al., 2015; Qi et al., 2015; Reuter et al., 2015; Schlunk et al., 2015; Soliman et al., 2015; Zhu et al., 2015). The antioxidant advantages of H2 gas included: 1) its high biomembrane penetration and intracellular diffusion capability which enable it to reach subcellular compart- ments like mitochondria; and 2) selectively scavenging the deleterious hydroxyl radical while preserving other important reactive oxygen and nitrogen species for normal signaling regulation. It is superior to some antioxidant supplements with strong reductive activity such as vitamin C or vitamin E to avoid the increased risk of mortality (Ohsawa et al., 2007). Since this landmark publication © 2016 Medical Gas Research | Published by Wolters Kluwer - Medknow 219

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