Protective Effects of Hydrogen against Irradiation

Radiation-induced lung injury is characterized by an acute pneumonia phase followed by a fibrotic phase. At the time of irradiation, a rapid, short-lived burst of reactive oxygen species (ROS) such as hydroxyl radicals (•OH) occurs, but chronic radiation-induced lung injury may occur due to excess ROS such as H₂O₂, O2•-, ONOO-, and •OH. Molecular hydrogen (H₂) is an efficient antioxidant that quickly diffuses cell membranes, reduces ROS such as •OH and ONOO-, and suppresses damage caused by oxidative stress in various organs. In 2011, through the evaluation of electron-spin resonance and fluorescent indicator signals, we had reported that H₂ can eliminate •OH and can protect against oxidative stress-related apoptotic damage induced by irradiation of cultured lung epithelial cells. We had explored for the first time the radioprotective effects of H₂ treatment on acute and chronic radiation-induced lung damage in mice by inhaled H2 gas (for acute) and imbibed H₂-enriched water (for chronic). Thus, we had proposed that H₂ be considered a potential radioprotective agent. Recent publications have shown that H₂ directly neutralizes highly reactive oxidants and indirectly reduces oxidative stress by regulating the expression of various genes. By regulating gene expression, H₂ functions as an anti-inflammatory and anti-apoptotic molecule and promotes energy metabolism. The increased evidence obtained from cultured cells or animal experiments reveal a putative place for H₂ treatment and its radioprotective effect clinically. This review focuses on major scientific advances in the treatment of H₂ as a new class of radioprotective agents.