Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Basic Clin Pharmacol Toxicol. 2010 Sep;107(3):703-8. doi: 10.1111/j.1742-7843.2010.00561.x. Epub 2010 Apr 12.
Concurrent administration of chloramphenicol (CAP) with multivitamin-haematinics complex (MHC) is a common practice to cushioning anticipated anaemic effect of CAP in most developing countries. This study investigated the mechanism involved in CAP-induced reproductive toxicity as well as the effects of its co-administration with MHC in male rats. CAP and MHC were administered orally at therapeutic doses of 28 mg/kg body-weight and 0.08 ml/kg body-weight, respectively, every 6 hr for 10 days. After exposure, while there was body-weight loss in CAP, MHC and CAP plus MHC-treated animals, there were no treatment-related changes in the absolute and relative weights of the testes in all treated groups. Alone, MHC treatment markedly decreased catalase (CAT), glutathione S-transferase (GST), and 5' nucleotidase (5' NTD) activities whereas it resulted in significant increase in superoxide dismutase (SOD) activity. Activities of SOD, CAT and GST as well as H(2)O(2) levels were not significantly affected in CAP and CAP plus MHC-treated rats whereas GSH level and 5' NTD activity were markedly decreased in CAP plus MHC-treated rats. Significant increase in testicular alkaline phosphatase activity, lipid peroxidation and sperm abnormalities were accompanied by reduction in epididymal sperm number, sperm motility and live-dead ratio in all treatment groups whereas aminotransferase activities were unaffected. Treatment-related degeneration of the testes was evident in all treated animals. In summary, while MHC-induced testicular toxicity via oxidative stress, CAP did not and their combination is implicated in reproductive dysfunction within the time course of our investigation.
同时给予氯霉素(CAP)和多种维生素-血红素复合物(MHC)是大多数发展中国家缓解 CAP 预期贫血作用的常见做法。本研究旨在探讨 CAP 诱导的生殖毒性的机制,以及其与 MHC 联合给药对雄性大鼠的影响。CAP 和 MHC 分别以 28mg/kg 体重和 0.08ml/kg 体重的治疗剂量,每 6 小时口服给药一次,共 10 天。暴露后,CAP 组动物体重减轻,MHC 和 CAP+MHC 组动物体重减轻,但所有治疗组的睾丸绝对重量和相对重量均无治疗相关变化。单独给予 MHC 治疗可显著降低过氧化氢酶(CAT)、谷胱甘肽 S-转移酶(GST)和 5'核苷酸酶(5'NTD)的活性,同时显著增加超氧化物歧化酶(SOD)的活性。SOD、CAT 和 GST 的活性以及 H2O2 水平在 CAP 和 CAP+MHC 处理的大鼠中没有显著影响,而 CAP+MHC 处理的大鼠中 GSH 水平和 5'NTD 活性显著降低。所有治疗组大鼠睾丸碱性磷酸酶活性、脂质过氧化和精子异常均显著增加,附睾精子数量、精子活力和活死比例均降低,而氨基转移酶活性不受影响。所有治疗动物的睾丸均出现与治疗相关的退行性改变。综上所述,MHC 通过氧化应激引起睾丸毒性,而 CAP 则没有,它们的联合使用可能与我们研究时间内的生殖功能障碍有关。