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α-硫辛酸可抑制睾丸中的氧化应激,并减轻胚胎期接触卡比马唑的大鼠的睾丸毒性。

α-lipoic acid inhibits oxidative stress in testis and attenuates testicular toxicity in rats exposed to carbimazole during embryonic period.

作者信息

Prathima P, Venkaiah K, Pavani R, Daveedu T, Munikumar M, Gobinath M, Valli M, Sainath S B

机构信息

Department of Biotechnology, Vikrama Simhapuri University, Nellore-524003, AP, India, India.

Biomedical Informatics Centre, National Institute of Nutrition-ICMR, Jamia Islamia (Post), Hyderabad-500007, Telangana, India, India.

出版信息

Toxicol Rep. 2017 Jun 23;4:373-381. doi: 10.1016/j.toxrep.2017.06.009. eCollection 2017.

Abstract

The aim of this study was to evaluate the probable protective effect of α-lipoic acid against testicular toxicity in rats exposed to carbimazole during the embryonic period. Time-mated pregnant rats were exposed to carbimazole from the embryonic days 9-21. After completion of the gestation period, all the rats were allowed to deliver pups and weaned. At postnatal day 100, F1 male pups were assessed for the selected reproductive endpoints. Gestational exposure to carbimazole decreased the reproductive organ indices, testicular daily sperm count, epididymal sperm variables ., sperm count, viable sperm, motile sperm and HOS-tail coiled sperms. Significant decrease in the activity levels of 3β- and 17β-hydroxysteroid dehydrogenases and expression of StAR mRNA levels with a significant increase in the total cholesterol levels were observed in the testis of experimental rats over the controls. These events were also accompanied by a significant reduction in the serum testosterone levels in CBZ exposed rats, indicating reduced steroidogenesis. In addition, the deterioration of the testicular architecture and reduced fertility ability were noticed in the carbimazole exposed rats. Significant reduction in the activity levels of superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase and reduced glutathione content with a significant increase in the levels of lipid peroxidation were observed in the testis of carbimazole exposed rats over the controls. Conversely, supplementation of α-lipoic acid (70 mg/Kg bodyweight) ameliorated the male reproductive health in rats exposed to carbimazole during the embryonic period as evidenced by enhanced reproductive organ weights, selected sperm variables, testicular steroidogenesis, and testicular enzymatic and non-enzymatic antioxidants. To conclude, diminished testicular antioxidant balance associated with reduced spermatogenesis and steroidogenesis might be responsible for the suppressed reproduction in rats exposed to the carbimazole transplacentally. On the other hand, α-lipoic acid through its antioxidant and steroidogenic properties mitigated testicular toxicity which eventually restored the male reproductive health of carbimazole-exposed rats.

摘要

本研究的目的是评估α-硫辛酸对胚胎期接触卡比马唑的大鼠睾丸毒性的可能保护作用。将定时交配的怀孕大鼠在胚胎第9至21天暴露于卡比马唑。妊娠期结束后,让所有大鼠产仔并断奶。在出生后第100天,对F1雄性幼崽进行选定的生殖终点评估。妊娠期接触卡比马唑会降低生殖器官指数、睾丸每日精子计数、附睾精子变量,即精子计数、活精子、活动精子和HOS尾部卷曲精子。与对照组相比,实验大鼠睾丸中3β-和17β-羟基类固醇脱氢酶的活性水平以及StAR mRNA水平的表达显著降低,总胆固醇水平显著升高。这些情况还伴随着卡比马唑暴露大鼠血清睾酮水平的显著降低,表明类固醇生成减少。此外,在卡比马唑暴露的大鼠中还发现了睾丸结构的恶化和生育能力的降低。与对照组相比,卡比马唑暴露大鼠睾丸中超氧化物歧化酶、过氧化氢酶、谷胱甘肽还原酶、谷胱甘肽过氧化物酶的活性水平和还原型谷胱甘肽含量显著降低,脂质过氧化水平显著升高。相反,补充α-硫辛酸(70毫克/千克体重)改善了胚胎期接触卡比马唑的大鼠的雄性生殖健康,这表现为生殖器官重量增加、选定的精子变量改善、睾丸类固醇生成以及睾丸酶促和非酶促抗氧化剂水平提高。总之,与精子发生和类固醇生成减少相关的睾丸抗氧化平衡减弱可能是经胎盘接触卡比马唑的大鼠生殖受抑制的原因。另一方面,α-硫辛酸通过其抗氧化和类固醇生成特性减轻了睾丸毒性,最终恢复了卡比马唑暴露大鼠的雄性生殖健康。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e48a/5615143/7f9d79da9aaf/fx1.jpg

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