Mechanisms Underlying the Biological Effects of Molecular Hydrogen

Aberrant redox-sensitive reactions and accumulation of oxidative damage can impair body functions and contribute to the development of various pathologies and aging. Although antioxidant substances have long been recognized as a measure of alleviating oxidative stress and restoring redox balance, the arsenal of effective means of preventing the development of various disorders, is still limited. There is an emerging field that utilizes molecular hydrogen (H₂) as a scavenger of free radicals and reactive oxygen species (ROS). Among the remarkable characteristics of H₂ is its ability to counteract the harmful effects of hydroxyl radical and peroxynitrite without affecting the activity of functionally important ROS, such as hydrogen peroxide and nitric oxide. The beneficial effects of H₂ have been documented in numerous clinical studies and studies on animal models and cell cultures. However, the established scavenging activity of H₂ can only partially explain its beneficial effects because the effects are achieved at very low concentrations of H₂. Given the rate of H₂ diffusion, such low concentrations may not be sufficient to scavenge continuously generated ROS. H₂ can also act as a signaling molecule and induce defense responses. However, the exact targets and mechanism(s) by which H₂ exerts these effects are unknown. Here, we analyzed both positive and negative effects of the endogenous H₂, identified the redox-sensitive components of the pathways affected by molecular hydrogen, and also discussed the potential role of molecular hydrogen in regulating cellular redox.