Molecular hydrogen: a preventive and therapeutic medical gas for various diseases

Li Ge,1Ming Yang,2Na-Na Yang,3Xin-Xin Yin,2 and  Wen-Gang Song4

Since the 2007 discovery that molecular hydrogen (H2) has selective antioxidant properties, multiple studies have shown that H2 has beneficial effects in diverse animal models and human disease. This review discusses H2 biological effects and potential mechanisms of action in various diseases, including metabolic syndrome, organ injury, and cancer; describes effective H2 delivery approaches; and summarizes recent progress toward H2 applications in human medicine. We also discuss remaining questions in H2 therapy, and conclude with an appeal for a greater role for H2 in the prevention and treatment of human ailments that are currently major global health burdens. This review makes a case for supporting hydrogen medicine in human disease prevention and therapy.

Oxidative stress in the cell results from the robust oxidizing potential of excess reactive oxygen species (ROS) [1]. Acute oxidative stress may result from various conditions, such as vigorous exercise, inflammation, ischemia and reperfusion (I/R) injury, surgical bleeding, and tissue transplantation [24]. Chronic/persistent oxidative stress is closely related to the pathogenesis of many lifestyle-related diseases, aging, and cancer [58]. However, many clinically tested antioxidants exhibit high toxicity levels that limit their usage to a narrow range of therapeutic dosages, and result in ineffective prevention of oxidative stress-related diseases [9]. Thus, identifying effective antioxidants with little-to-no side effects is very important for the treatment of multiple diseases.

H2 is a flammable, colorless, odorless gas that can act as a reducing agent under certain circumstances. It was previously considered physiologically inert in mammalian cells, and was not thought to react with active substrates in biological systems. Recently, H2 has emerged as a novel medical gas with potentially broad applications. Dole, et al. first reported the therapeutic effects of H2 in 1975 in a skin squamous carcinoma mouse model [10]. Thereafter, inhaling high pressure H2 was demonstrated as a treatment for liver parasite infection-induced hepatitis [11]. In 2007, Ohsawa and colleagues discovered that H2 has antioxidant properties that protect the brain against I/R injury and stroke by selectively neutralizing hydroxyl radicals (·OH) and peroxynitrite(ONOO) [1].

To date, H2 preventive and therapeutic effects have been observed in various organs, including the brain, heart, pancreas, lung, and liver. H2 mediates oxidative stress and may exhibit anti-inflammatory and anti-apoptotic effects [1214]. H2 not only provides a safe and effective disease treatment mechanism, but also prompts researchers to re-visit the significance and benefits of medicinal gas in the human body. This review summarizes recent progress toward potential preventive and therapeutic applications of H2 and addresses possible underlying molecular mechanisms.


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