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The effect of bisphenol A on testicular steroidogenesis and its amelioration by quercetin: an in vivo and in silico approach†
Toxicology Research ( IF 2.1 ) Pub Date : 2017-09-14 00:00:00 , DOI: 10.1039/c7tx00161d
Sanman Samova 1, 2, 3, 4, 5 , Chirag N. Patel 2, 3, 6, 7, 8 , Hetal Doctor 1, 2, 3, 4, 5 , Himanshu A. Pandya 2, 3, 6, 7, 8 , R. J. Verma 1, 2, 3, 4, 5
Affiliation  

Bisphenol A (BPA), a phenyl ring containing synthetic xenoestrogen, is widely used in the manufacture of polycarbonate plastics, epoxy resins and as a non-polymer additive to other plastics. Food is considered as the main source of exposure to BPA as it leaches out from food containers as well as surface coatings. It causes toxicity in the liver, kidney, brain, and other organs by initiating the process of lipid peroxidation. The present investigation was an attempt to evaluate the effect of BPA on steroidogenesis and its amelioration by quercetin. Inbred Swiss strain male albino mice were orally administered with 80, 120 and 240 mg per kg body weight per day of BPA for 45 days. The results revealed that BPA causes significant (p < 0.05) and dose-dependent changes in the body weight and biochemical parameters like protein, cholesterol and lipid contents as well as activities of 3β-and 17β-hydroxysteroid dehydrogenases in the testis of mice. It was also found to significantly reduce the testosterone level in serum. Oral administration of quercetin (30, 60 and 90 mg per kg body weight per day) along with a high dose of BPA (240 mg per kg body weight per day) for 45 days caused significant amelioration in the body weight and steroidogenesis as compared to the BPA alone treated group. The effect was dose-dependent. This amelioration in BPA-induced toxicity might be due to the antioxidative properties of quercetin. The reduction in the function of enzymes was confirmed by in silico bindings. BPA and quercetin show competitive binding with steroidogenic enzymes as well as binding with each other. This could be a possible mechanism to reduce the toxic effect of BPA which has been supported by molecular dynamics simulations for molecular level recognition with structural insights.

中文翻译:

双酚A对睾丸类固醇生成的作用及其槲皮素的改善作用:体内计算机方法

双酚A(BPA)是一种含苯环的合成异雌激素,被广泛用于制造聚碳酸酯塑料,环氧树脂以及作为其他塑料的非聚合物添加剂。从食物容器和表面涂层中渗出的食物被认为是接触BPA的主要来源。它通过引发脂质过氧化作用而在肝脏,肾脏,大脑和其他器官中引起毒性。本研究是评估双酚A对类固醇生成及其槲皮素改善作用的尝试。对自交系瑞士白种雄性白化病小鼠口服给予每公斤体重每天80、120和240 mg的BPA,持续45天。结果表明,双酚A引起显着(p<0.05)以及小鼠睾丸中体重和生物化学参数(如蛋白质,胆固醇和脂质含量以及3β-和17β-羟类固醇脱氢酶的活性)的剂量依赖性变化。还发现它可以显着降低血清中的睾丸激素水平。与45天相比,口服槲皮素(每公斤体重每天30、60和90毫克)以及高剂量的BPA(每天每公斤体重240毫克)导致体重和类固醇生成明显改善BPA单独治疗组。效果是剂量依赖性的。BPA诱导的毒性的这种改善可能是由于槲皮素的抗氧化特性所致。酶的功能降低已通过计算机确认绑定。BPA和槲皮素显示出与类固醇生成酶的竞争性结合以及彼此之间的结合。这可能是降低BPA毒性作用的一种可能机制,这已经得到了分子动力学模拟的支持,具有结构上的洞察力,可用于分子水平的识别。
更新日期:2017-09-14
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