Prathima P, Venkaiah K, Daveedu T, Pavani R, Sukeerthi S, Gopinath M, Sainath Sri Bhashaym
Department of Biotechnology, Vikrama Simhapuri University, Nellore, AP 524 320 India.
Department of Pharmacy, Ratnam Pharmacy College, Muthukur, Nellore, AP India.
Toxicol Res. 2020 Mar 3;36(4):343-357. doi: 10.1007/s43188-019-00036-y. eCollection 2020 Oct.
Linuron is well known for its antiandrogenic property. However, the effects of linuron on testicular and epididymal pro- and antioxidant status are not well defined. On the other hand, α-lipoic acid is well known as universal antioxidant. Therefore, the purpose of this study was twofold: firstly to investigate whether linuron exposure alters antioxidant status in the testis and epididymis of rats and if so, whether the supplementation of α-lipoic acid mitigates linuron-induced oxidative toxicity in rats. To address this question, α-lipoic acid at a dose of 70 mg/Kg body weight (three times a week) was administered to linuron exposed rats (10 or 50 mg/Kg body weight, every alternate day over a period of 60 days), and the selected reproductive endpoints were analyzed after 60 days. Respective controls were maintained in parallel. Linuron at selected doses reduced testicular daily sperm count, and epididymal sperm count, sperm motility, sperm viability, and number of tail coiled sperm, reduced activity levels of 3β- and 17β-hydroxysteroid dehydrogenases, decreased expression levels of StAR mRNA, inhibition of testosterone levels, and elevated levels of testicular cholesterol in rats over controls. Linuron intoxication deteriorated the structural integrity of testis and epididymis associated with reduced the reproductive performance over controls. Conversely, α-lipoic acid supplementation enhanced sperm quality and improved the testosterone synthesis pathway in linuron exposed rats over its respective control. Administration of α-lipoic acid restored inhibition of testicular and epididymal enzymatic (superoxide dismutase, catalase, glutathione reductase, glutathione peroxidise) and non-enzymatic (glutathione content), increased lipid peroxidation and protein carbonyl content produced by linuron in rats. α-lipoic acid supplementation inhibited the expression levels of testicular caspase-3 mRNA levels and also its activity in linuron treated rats. To summate, α-lipoic acid-induced protection of reproductive health in linuron treated rats could be attributed to its antioxidant, and steroidogenic properties.
利谷隆以其抗雄激素特性而闻名。然而，利谷隆对睾丸和附睾的促氧化和抗氧化状态的影响尚不明确。另一方面，α-硫辛酸是众所周知的通用抗氧化剂。因此，本研究的目的有两个：首先，研究暴露于利谷隆是否会改变大鼠睾丸和附睾中的抗氧化状态，如果是，补充α-硫辛酸是否能减轻利谷隆对大鼠的氧化毒性。为了解决这个问题，给暴露于利谷隆的大鼠（10或50mg/kg体重，每隔一天给药，持续60天）以70mg/kg体重的剂量（每周三次）施用α-硫辛酸，60天后分析选定的生殖终点。分别设置平行的对照组。与对照组相比，选定剂量的利谷隆降低了大鼠睾丸每日精子计数、附睾精子计数、精子活力、精子存活率和尾部卷曲精子数量，降低了3β-和17β-羟基类固醇脱氢酶的活性水平，降低了类固醇生成急性调节蛋白（StAR）mRNA的表达水平，抑制了睾酮水平，并提高了睾丸胆固醇水平。利谷隆中毒使睾丸和附睾的结构完整性恶化，与对照组相比生殖性能降低。相反，与各自的对照组相比，补充α-硫辛酸提高了暴露于利谷隆的大鼠的精子质量，并改善了睾酮合成途径。施用α-硫辛酸恢复了利谷隆对大鼠睾丸和附睾中酶促（超氧化物歧化酶、过氧化氢酶、谷胱甘肽还原酶、谷胱甘肽过氧化物酶）和非酶促（谷胱甘肽含量）的抑制作用，增加了利谷隆在大鼠体内产生的脂质过氧化和蛋白质羰基含量。补充α-硫辛酸抑制了利谷隆处理的大鼠睾丸中半胱天冬酶-3 mRNA水平及其活性。总之，α-硫辛酸对利谷隆处理的大鼠生殖健康的保护作用可能归因于其抗氧化和类固醇生成特性。
