Yeh Yueh-Chiao, Lai Hui-Chin, Ting Chih-Tai, Lee Wen-Lieng, Wang Li-Chuan, Wang Kuo-Yang, Lai Hui-Chun, Liu Tsun-Jui
Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan.
Biochem Pharmacol. 2007 Oct 1;74(7):969-80. doi: 10.1016/j.bcp.2007.06.031. Epub 2007 Jun 26.
Spermatogenic cells constitute one of the body tissues that are susceptible to doxorubicin-induced oxidative stress and apoptosis. To explore whether doxorubicin toxicity to these male germ cells could be prevented by adjuvant medication, this study was designed to examine the possible ameliorating action of doxycycline, an antibiotic with anti-oxidant property, on doxorubicin-induced oxidative and apoptotic effects in mouse testes. Male mice at 5-week of age were treated with vehicles, doxorubicin alone (3 mg/kg, i.p. every other day for 3 doses), doxycycline alone (2.5 mg/kg, i.p. every other day for 3 doses), or doxycycline plus doxorubicin (each dose given 1 day post-doxycycline). After 28 days, mice treated with doxorubicin alone displayed smaller body and testicular weights, reduced sperm counts, impaired spermatogenic capability (scarcer spermatids and spermatocytes), increased oxidative stress (malondialdehyde levels), decreased anti-oxidant activity (superoxide dismutase and glutathione peroxidase), and elevated apoptotic indexes (upregulation of Bax and Bad, downregulation of Bcl-2 and Bcl-xL, release of cytochrome c from mitochondria to cytosol, activation of caspase-3, and increase of cleaved caspase-3 abundance and TUNEL positive cells), while doxycycline pretreatment could effectively prevent nearly all of these abnormalities. These results provide firm evidence that doxycycline pretreatment would offset the oxidative and apoptotic impact imposed by doxorubicin, and imply doxycycline to be a promising adjuvant agent that may attenuate the toxicity of doxorubicin on testicular tissues in clinical practice.
生精细胞是易受阿霉素诱导的氧化应激和细胞凋亡影响的身体组织之一。为了探究辅助用药是否可以预防阿霉素对这些雄性生殖细胞的毒性，本研究旨在检测具有抗氧化特性的抗生素多西环素对阿霉素诱导的小鼠睾丸氧化和凋亡效应的可能改善作用。5周龄雄性小鼠分别接受溶剂对照、单独阿霉素（3mg/kg，腹腔注射，隔日1次，共3剂）、单独多西环素（2.5mg/kg，腹腔注射，隔日1次，共3剂）或多西环素加阿霉素（多西环素给药1天后给予各剂量阿霉素）处理。28天后，单独接受阿霉素处理的小鼠体重和睾丸重量较小，精子数量减少，生精能力受损（精子细胞和精母细胞较少），氧化应激增加（丙二醛水平升高），抗氧化活性降低（超氧化物歧化酶和谷胱甘肽过氧化物酶），凋亡指数升高（Bax和Bad上调，Bcl-2和Bcl-xL下调，细胞色素c从线粒体释放到细胞质，caspase-3激活，裂解的caspase-3丰度和TUNEL阳性细胞增加），而多西环素预处理可有效预防几乎所有这些异常。这些结果提供了确凿的证据，表明多西环素预处理可抵消阿霉素施加氧化和凋亡影响，并表明多西环素可能是一种有前景的辅助药物，在临床实践中可能减轻阿霉素对睾丸组织的毒性。
