Oyeyipo Ibukun P, Skosana Bongekile T, Everson Frans P, Strijdom Hans, du Plessis Stefan S
Division of Medical Physiology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa.
Department of Physiology, College of Health Sciences, Osun State University, Osogbo, Osun State, Nigeria.
Toxicol Res. 2018 Jan;34(1):41-48. doi: 10.5487/TR.2018.34.1.041. Epub 2018 Jan 15.
The efficacy of highly active antiretroviral therapy (HAART) has led to an increase demand for therapeutic use, thereby necessitating investigation into drug toxicity. This study was designed to investigate the effects of HAART on sperm parameters and testicular oxidative stress in lean and obese rats. Wistar rats (males, n = 40, weighing 180~200 g) were assigned randomly into 4 groups and treated accordingly for 16 weeks as follows: Control (C): lean group fed with standard rat chow; Diet induced obesity (DIO): obese animals fed a high caloric diet; C + ART: lean animals treated with HAART; DIO + ART: obese animals treated with HAART. An antiretroviral drug combination of Tenofovir, Emtricitabine and Efavirenz at a dose of 17, 26 and 50 mg/kg/day was administered for the latter 6 weeks via jelly cube feeding. At the end of the experimental period, sperm analysis was performed on sperm collected from the caudal epididymis, while the testis was homogenized for antioxidant enzyme and lipid peroxidation assays. Results showed that HAART significantly decreased sperm motility ( < 0.05) in both lean and obese animals, and viability ( < 0.05) in the DIO group. Testicular glutathione, catalase and superoxide dismutase were significantly decreased ( < 0.05), while Thiobarbituric acid reactive substances (TBARS) levels were significantly increased ( < 0.05) when the DIO+ART group was compared to Control group. Thus, the decreased sperm qualities associated with HAART might be as a result of increased testicular oxidative stress prominent in obese animals.
高效抗逆转录病毒疗法（HAART）的疗效导致其治疗用途的需求增加，因此有必要对药物毒性进行研究。本研究旨在调查HAART对瘦型和肥胖型大鼠精子参数及睾丸氧化应激的影响。将雄性Wistar大鼠（n = 40，体重180~200 g）随机分为4组，并按以下方式相应处理16周：对照组（C）：喂食标准大鼠饲料的瘦型组；饮食诱导肥胖组（DIO）：喂食高热量饮食的肥胖动物组；C + ART组：接受HAART治疗的瘦型动物组；DIO + ART组：接受HAART治疗的肥胖动物组。在最后6周，通过果冻方块喂食给予剂量为17、26和50 mg/kg/天的替诺福韦、恩曲他滨和依非韦伦的抗逆转录病毒药物组合。实验期结束时，对从附睾尾部收集的精子进行精子分析，同时将睾丸匀浆用于抗氧化酶和脂质过氧化测定。结果显示，HAART显著降低了瘦型和肥胖型动物的精子活力（<0.05），以及DIO组的精子存活率（<0.05）。与对照组相比，DIO + ART组的睾丸谷胱甘肽、过氧化氢酶和超氧化物歧化酶显著降低（<0.05），而硫代巴比妥酸反应性物质（TBARS）水平显著升高（<0.05）。因此，与HAART相关的精子质量下降可能是由于肥胖动物中突出的睾丸氧化应激增加所致。
