Kumar Thimmappa R
Scientist, Department of Biochemistry & Nutrition, CFTRI, Mysore-570 020, India.
J Androl. 2007 Jan-Feb;28(1):77-85. doi: 10.2164/jandrol.106.000265. Epub 2006 Aug 23.
The present study describes the extent and pattern of oxidative stress induction in testis and epididymal sperm of rats following in vivo exposure to repeated sublethal doses of 2 model pro-oxidants, namely, t-butyl hydroperoxide (tbHP) and cumene hydroperoxide (cHP). Single sublethal (1/40, 1/20, and 1/10 LD(50)) doses of hydroperoxides (HP) administered intraperitoneally to male rats (CFT-Wistar strain) failed to induce any significant increase in malondialdehyde or reactive oxygen species (ROS) levels in testis or epididymal sperm. However, repeated doses for 1 or 2 weeks induced a marked dose-related enhancement of lipid peroxidation (LPO) and ROS levels in both testis and epididymal sperm. Further evidence, such as significant perturbations in both enzymic and nonenzymic antioxidants and enhanced levels of protein carbonyls in testis, suggested induction of oxidative stress. In testis, moderate depletion in reduced glutathione levels and marked diminution in ascorbic acid and alpha-tocopherol content were accompanied by increased activities of various antioxidant enzymes, namely glutathione peroxidase, glutathione-S-transferase, and catalase, in both the HP treatments. Furthermore, significant alterations in the specific activities of testicular enzymes such as LDH-X, G-6-PDH, and SDH indicated altered testicular physiology. Both HP at higher doses induced significant DNA damage (determined by fluorimetric analysis of DNA unwinding assay) in testis and epididymal sperm. Increased total iron levels in testis of HP-treated rats are indicative of the possible involvement of iron-mediated free radical reactions in this model. These findings provide an account of early oxidative damage in testis and epididymal sperm following short-term exposure to HP in vivo, and this model is being further exploited for understanding the consequences of chronic oxidative stress-mediated alterations for the physiology of male reproductive system and its implications for fertility.
本研究描述了大鼠在体内反复接触两种模型促氧化剂（即叔丁基过氧化氢（tbHP）和异丙苯过氧化氢（cHP））的亚致死剂量后，睾丸和附睾精子中氧化应激诱导的程度和模式。对雄性大鼠（CFT-Wistar品系）腹腔注射单一亚致死剂量（1/40、1/20和1/10 LD(50)）的氢过氧化物（HP），未能诱导睾丸或附睾精子中丙二醛或活性氧（ROS）水平有任何显著增加。然而，连续1或2周重复给药会导致睾丸和附睾精子中脂质过氧化（LPO）和ROS水平出现明显的剂量相关增强。进一步的证据，如酶促和非酶促抗氧化剂的显著紊乱以及睾丸中蛋白质羰基水平的升高，表明氧化应激被诱导。在睾丸中，两种HP处理均导致还原型谷胱甘肽水平适度降低，抗坏血酸和α-生育酚含量显著减少，同时各种抗氧化酶（即谷胱甘肽过氧化物酶、谷胱甘肽-S-转移酶和过氧化氢酶）的活性增加。此外，睾丸酶（如LDH-X、G-6-PDH和SDH）的比活性发生显著变化，表明睾丸生理发生改变。两种较高剂量的HP均在睾丸和附睾精子中诱导了显著的DNA损伤（通过DNA解旋试验的荧光分析确定）。HP处理大鼠睾丸中铁总水平的增加表明该模型中可能涉及铁介导的自由基反应。这些发现说明了大鼠在体内短期接触HP后睾丸和附睾精子的早期氧化损伤情况，并且该模型正在被进一步用于了解慢性氧化应激介导的改变对雄性生殖系统生理的影响及其对生育能力的影响。
