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).

Molecular hydrogen (H2) is clinically administered; however, in some hospitals, H2 is given to patients without consideration of its safe use. In the present study, we prepared convenient and safe devices for the drinking of super-saturated H2 water, for intravenous drip infusion of H2-rich saline, and for the inhalation of H2 gas. In order to provide useful information for researchers using these devices, the changes in H2 concentration were studied. Our experimental results should contribute to the advance of non-clinical and clinical research in H2 medicine.

Intestinal bacteria can be classified into “beneficial bacteria” and “harmful bacteria.” However, it is difficult to explain the mechanisms that make “beneficial bacteria” truly beneficial to human health. This issue can be addressed by focusing on hydrogen-producing bacteria in the intestines. Although it is widely known that molecular hydrogen can react with hydroxyl radicals, generated in the mitochondria, to protect cells from oxidative stress, the beneficial effects of hydrogen are not fully pervasive because it is not generally thought to be metabolized in vivo. In recent years, it has become clear that there is a close relationship between the amount of hydrogen produced by intestinal bacteria and various diseases, and this report discusses this relationship.

Hydrogen (H₂) is promising as an energy source for the next generation. Medical applications using H₂ gas can be also considered as a clean and economical technology. Since the H₂ gas based on electrolysis of water production has potential to expand the medical applications, the technology has been developed in order to safely dilute it and to supply it to the living body by inhalation, respectively. H₂ is an inert molecule which can scavenge the highly active oxidants including hydroxyl radical (·OH) and peroxynitrite (ONOO⁻), and which can convert them into water. H₂ is clean and causes no adverse effects in the body. The mechanism of H₂ is different from that of traditional drugs because it works on the root of many diseases. Since H₂ has extensive and various effects, it may be called a “wide spectrum molecule” on diseases. In this paper, we reviewed the current medical applications of H₂ including its initiation and development, and we also proposed its prospective medical applications. Due to its marked efficacy and no adverse effects, H₂ will be a next generation therapy candidate for medical applications.

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.