Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Department of Anatomy, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Biochem Biophys Res Commun. 2018 Sep 3;503(1):171-176. doi: 10.1016/j.bbrc.2018.05.205. Epub 2018 Jun 5.
Exposure to pesticide chlorpyrifos (CPF) has been implicated in reproductive deficits in both humans and animals. Diphenyl diselenide (DPDS) is an organoselenium compound widely reported to elicit potent pharmacological activities in several chemically-induced toxicity and disease models. However, there is paucity of scientific information on the influence of DPDS on CPF-induced reproductive dysfunction. The present study investigated the influence of DPDS on CPF-induced functional changes along the hypothalamic-pituitary- testicular axis in rats. CPF was administered alone at 5 mg/kg body weight or orally co-treated with DPDS at 2.5 and 5 mg/kg body weight for 35 consecutive days. Results showed that DPDS co-treatment significantly (p < 0.05) abrogated CPF-induced oxidative stress by increasing the antioxidant enzymes activities and glutathione content, decreasing the hydrogen peroxide and lipid peroxidation levels in the hypothalamus, testes and epididymis of the treated rats. Moreover, DPDS co-treatment significantly ameliorated CPF-induced histological alterations in the hypothalamus, testes and epididymis of the treated rats. Besides, the significant augmentation of luteinizing hormone, follicle-stimulating hormone and testosterone levels as well as the testicular activities of acid phosphatase, alkaline phosphatase and lactate dehydrogenase by DPDS was accompanied by an increase in sperm quality and quantity in the treated rats. Taken together, DPDS abrogates CPF mediated toxicity along the hypothalamic-pituitary-testicular axis in rats via inhibition of lipid peroxidation, enhancement of antioxidant enzymes activities and testicular function. Thus, DPDS may be a possible chemoprotective drug candidate against CPF-induced male reproductive deficits in humans.
接触杀虫剂毒死蜱（CPF）已被牵连到人类和动物的生殖缺陷中。二苯二硒醚（DPDS）是一种有机硒化合物，广泛报道其在几种化学诱导的毒性和疾病模型中具有强大的药理活性。然而，关于 DPDS 对 CPF 诱导的生殖功能障碍的影响，科学信息仍然很少。本研究调查了 DPDS 对 CPF 诱导的大鼠下丘脑-垂体-睾丸轴功能变化的影响。CPF 单独以 5mg/kg 体重给药或口服与 DPDS 以 2.5 和 5mg/kg 体重共处理 35 天。结果表明，DPDS 共处理通过增加抗氧化酶活性和谷胱甘肽含量，降低下丘脑、睾丸和附睾中过氧化氢和脂质过氧化水平，显著（p<0.05）阻断 CPF 诱导的氧化应激。此外，DPDS 共处理显著改善了 CPF 诱导的大鼠下丘脑、睾丸和附睾的组织学改变。此外，DPDS 共处理伴随着黄体生成素、卵泡刺激素和睾酮水平的显著增加以及酸性磷酸酶、碱性磷酸酶和乳酸脱氢酶的睾丸活性的增加，还增加了处理大鼠的精子质量和数量。总之，DPDS 通过抑制脂质过氧化、增强抗氧化酶活性和睾丸功能，阻断 CPF 介导的大鼠下丘脑-垂体-睾丸轴毒性。因此，DPDS 可能是一种针对人类 CPF 诱导的男性生殖缺陷的潜在化学保护药物候选物。
