Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan.
Curr Pharm Des. 2021;27(5):679-686. doi: 10.2174/1381612827666210119103545.
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 HO, O2•-, ONOO-, and •OH. Molecular hydrogen (H) 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 H 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 H treatment on acute and chronic radiation-induced lung damage in mice by inhaled H2 gas (for acute) and imbibed H-enriched water (for chronic). Thus, we had proposed that H be considered a potential radioprotective agent. Recent publications have shown that H directly neutralizes highly reactive oxidants and indirectly reduces oxidative stress by regulating the expression of various genes. By regulating gene expression, H 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 H treatment and its radioprotective effect clinically. This review focuses on major scientific advances in the treatment of H as a new class of radioprotective agents.
放射性肺损伤的特征是急性肺炎期,随后是纤维化期。在照射时,会迅速产生短暂的活性氧(ROS)爆发,例如羟基自由基(•OH),但慢性放射性肺损伤可能由于过量的 ROS 如 HO、O2•-、ONOO-和•OH 而发生。氢气(H)是一种有效的抗氧化剂,可快速扩散细胞膜,减少•OH 和 ONOO-等 ROS,并抑制各种器官中氧化应激引起的损伤。2011 年,通过电子自旋共振和荧光指示剂信号的评估,我们报告说 H 可以消除•OH,并可以防止培养的肺上皮细胞照射引起的与氧化应激相关的凋亡损伤。我们首次通过吸入 H2 气体(急性)和饮用富含 H 的水(慢性)探索了 H 处理对急性和慢性放射性肺损伤的放射防护作用。因此,我们提出 H 可以被认为是一种有潜力的放射防护剂。最近的出版物表明,H 通过调节各种基因的表达直接中和高反应性氧化剂,并间接降低氧化应激。通过调节基因表达,H 作为一种抗炎和抗凋亡分子发挥作用,并促进能量代谢。从培养细胞或动物实验中获得的更多证据揭示了 H 治疗及其放射防护作用在临床上的潜在用途。本综述重点介绍了 H 作为一类新型放射防护剂治疗的主要科学进展。