Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan.
Am J Physiol Lung Cell Mol Physiol. 2011 Oct;301(4):L415-26. doi: 10.1152/ajplung.00008.2011. Epub 2011 Jul 15.
Molecular hydrogen (H(2)) is an efficient antioxidant that diffuses rapidly across cell membranes, reduces reactive oxygen species (ROS), such as hydroxyl radicals and peroxynitrite, and suppresses oxidative stress-induced injury in several organs. ROS have been implicated in radiation-induced damage to lungs. Because prompt elimination of irradiation-induced ROS should protect lung tissue from damaging effects of irradiation, we investigated the possibility that H(2) could serve as a radioprotector in the lung. Cells of the human lung epithelial cell line A549 received 10 Gy irradiation with or without H(2) treatment via H(2)-rich PBS or medium. We studied the possible radioprotective effects of H(2) by analyzing ROS and cell damage. Also, C57BL/6J female mice received 15 Gy irradiation to the thorax. Treatment groups inhaled 3% H(2) gas and drank H(2)-enriched water. We evaluated acute and late-irradiation lung damage after H(2) treatment. H(2) reduced the amount of irradiation-induced ROS in A549 cells, as shown by electron spin resonance and fluorescent indicator signals. H(2) also reduced cell damage, measured as levels of oxidative stress and apoptotic markers, and improved cell viability. Within 1 wk after whole thorax irradiation, immunohistochemistry and immunoblotting showed that H(2) treatment reduced oxidative stress and apoptosis, measures of acute damage, in the lungs of mice. At 5 mo after irradiation, chest computed tomography, Ashcroft scores, and type III collagen deposition demonstrated that H(2) treatment reduced lung fibrosis (late damage). This study thus demonstrated that H(2) treatment is valuable for protection against irradiation lung damage with no known toxicity.
氢气（H2）是一种有效的抗氧化剂，能够快速扩散穿过细胞膜，减少活性氧物种（ROS），如羟基自由基和过氧亚硝酸盐，并抑制氧化应激诱导的多个器官损伤。ROS 被认为与肺部辐射损伤有关。由于迅速消除辐射诱导的 ROS 应该可以保护肺组织免受辐射的损伤作用，我们研究了 H2 作为肺部辐射防护剂的可能性。用富含 H2 的 PBS 或培养基通过 H2 处理来照射人肺上皮细胞系 A549 细胞 10 Gy。我们通过分析 ROS 和细胞损伤来研究 H2 的可能的辐射防护作用。此外，C57BL/6J 雌性小鼠接受胸部 15 Gy 照射。治疗组吸入 3%H2 气体并饮用富氢水。我们在 H2 处理后评估急性和晚期辐射性肺损伤。正如电子自旋共振和荧光指示剂信号所示，H2 减少了 A549 细胞中照射诱导的 ROS 量。H2 还降低了氧化应激和凋亡标志物的水平，从而降低了细胞损伤程度，提高了细胞活力。在整个胸部照射后 1 周内，免疫组织化学和免疫印迹显示 H2 治疗减少了小鼠肺部的氧化应激和凋亡，这是急性损伤的指标。在照射后 5 个月时，胸部计算机断层扫描、Ashcroft 评分和 III 型胶原蛋白沉积表明 H2 治疗减轻了肺纤维化（晚期损伤）。因此，这项研究表明 H2 治疗对防止辐射性肺损伤具有价值，且没有已知的毒性。
