Although ionizing radiation (radiation) is commonly used for medical diagnosis and cancer treatment, radiation-induced damages cannot be avoided. Such damages can be classified into direct and indirect damages, caused by the direct absorption of radiation energy into DNA and by free radicals, such as hydroxyl radicals (•OH), generated in the process of water radiolysis. More specifically, radiation damage concerns not only direct damages to DNA, but also secondary damages to non-DNA targets, because low-dose radiation damage is mainly caused by these indirect effects. Molecular hydrogen (H₂) has the potential to be a radioprotective agent because it can selectively scavenge •OH, a reactive oxygen species with strong oxidizing power. Animal experiments and clinical trials have reported that H₂ exhibits a highly safe radioprotective effect. This paper reviews previously reported radioprotective effects of H₂ and discusses the mechanisms of H₂, not only as an antioxidant, but also in intracellular responses including anti-inflammation, anti-apoptosis, and the regulation of gene expression. In doing so, we demonstrate the prospects of H₂ as a novel and clinically applicable radioprotective agent.

Mitochondria are the largest source of reactive oxygen species (ROS) and are intracellular organelles that produce large amounts of the most potent hydroxyl radical (·OH). Molecular hydrogen (H₂) can selectively eliminate ·OH generated inside of the mitochondria. Inflammation is induced by the release of proinflammatory cytokines produced by macrophages and neutrophils. However, an uncontrolled or exaggerated response often occurs, resulting in severe inflammation that can lead to acute or chronic inflammatory diseases. Recent studies have reported that ROS activate NLRP3 inflammasomes, and that this stimulation triggers the production of proinflammatory cytokines. It has been shown in literature that H₂ can be based on the mechanisms that inhibit mitochondrial ROS. However, the ability for H₂ to inhibit NLRP3 inflammasome activation via mitochondrial oxidation is poorly understood. In this review, we hypothesize a possible mechanism by which H₂ inhibits mitochondrial oxidation. Medical applications of H₂ may solve the problem of many chronic inflammation-based diseases, including coronavirus disease 2019 (COVID-19).

While many antitumor drugs have yielded unsatisfactory therapeutic results, drugs are one of the most prevalent therapeutic measures for the treatment of cancer. The development of cancer largely results from mutations in nuclear DNA, as well as from those in mitochondrial DNA (mtDNA). Molecular hydrogen (H₂), an inert molecule, can scavenge hydroxyl radicals (·OH), which are known to be the strongest oxidizing reactive oxygen species (ROS) in the body that causes these DNA mutations. It has been reported that H₂ has no side effects, unlike conventional antitumor drugs, and that it is effective against many diseases caused by oxidative stress and chronic inflammation. Recently, there has been an increasing number of papers on the efficacy of H₂ against cancer and its effects in mitigating the side effects of cancer treatment. In this review, we demonstrate the efficacy and safety of H₂ as a novel antitumor agent and show that its mechanisms may not only involve the direct scavenging of ·OH, but also other indirect biological defense mechanisms via the regulation of gene expression.

Mibyou, or pre-symptomatic diseases, refers to state of health in which a disease is slowly developing within the body yet the symptoms are not apparent. Common examples of mibyou in modern medicine include inflammatory diseases that are caused by chronic inflammation. It is known that chronic inflammation is triggered by the uncontrolled release of proinflammatory cytokines by neutrophils and macrophages in the innate immune system. In a recent study, it was shown that molecular hydrogen (H₂) has the ability to treat chronic inflammation by eliminating hydroxyl radicals (·OH), a mitochondrial reactive oxygen species (ROS). In doing so, H₂ suppresses oxidative stress, which is implicated in several mechanisms at the root of chronic inflammation, including the activation of NLRP3 inflammasomes. This review explains these mechanisms by which H₂ can suppress chronic inflammation and studies its applications as a protective agent against different inflammatory diseases in their pre-symptomatic state. While mibyou cannot be detected nor treated by modern medicine, H₂ is able to suppress the pathogenesis of pre-symptomatic diseases, and thus exhibits prospects as a novel protective agent.