Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, People's Republic of China.
Biochem J. 2012 Feb 15;442(1):49-56. doi: 10.1042/BJ20111786.
Our recent studies suggest that H2 (hydrogen) has a potential as a novel radioprotector without known toxic side effects. The present study was designed to examine the underlying radioprotective mechanism of H2 and its protective role on irradiated germ cells. Produced by the Fenton reaction and radiolysis of H2O, hydroxyl radicals (•OH) were identified as the free radical species that were reduced by H2. We used a H2 microelectrode to dynamically detect H2 concentration in vivo, and found H2 significantly reduced in situ fluorescence intensity of hydroxyphenyl fluorescein; however, as we treated the mice with H2 after irradiation, the decrease is not significant. We found that pre-treatment of H2 to IR (ionizing radiation) significantly suppressed the reaction of •OH and the cellular macromolecules which caused lipid peroxidation, protein carbonyl and oxidatively damaged DNA. The radioprotective effect of H2 on male germ cells was supported by ameliorated apoptotic findings examined by morphological changes and TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling) in testicular tissue, and by preserved viability of stem spermatogonia examined for testicular histological parameters, daily sperm production and sperm quality; we used WR-2721 [S-2-(3-aminopropylamino)ethyl phosphorothioic acid] as a reference compound. Our results represent the first in vivo evidence in support of a radioprotective role of H2 by neutralizing •OH in irradiated tissue with no side effects.
我们最近的研究表明，氢气（H2）作为一种新型的辐射防护剂具有潜力，且没有已知的毒副作用。本研究旨在探讨 H2 的潜在辐射防护机制及其对辐射生殖细胞的保护作用。通过 Fenton 反应和 H2O 的辐射分解产生的羟自由基（•OH）被确定为被 H2 还原的自由基。我们使用 H2 微电极在体内动态检测 H2 浓度，发现 H2 显著降低了羟苯基荧光素的原位荧光强度；然而，当我们在辐照后用 H2 处理小鼠时，降低幅度并不显著。我们发现，H2 预处理 IR（电离辐射）显著抑制了•OH 与细胞大分子的反应，这些反应导致了脂质过氧化、蛋白质羰基化和氧化损伤的 DNA。H2 对雄性生殖细胞的辐射防护作用得到了支持，这表现在睾丸组织形态学变化和 TUNEL（末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记）检测到的凋亡情况得到改善，以及睾丸组织学参数、每日精子产量和精子质量检测到的干细胞精原细胞活力得到保存；我们使用 WR-2721[ S-2-（3-氨基丙基氨基）乙基膦酸硫酯]作为参考化合物。我们的结果代表了支持 H2 通过中和辐照组织中的•OH 而无副作用发挥辐射防护作用的第一个体内证据。
