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通过计算机模拟和体外研究阐明 1HYN 和 1QKI 活性在 BPA 诱导毒性及其被没食子酸改善中的作用。

In silico and in vitro studies to elucidate the role of 1HYN and 1QKI activity in BPA induced toxicity and its amelioration by Gallic acid.

机构信息

Molecular Ecology and Toxicology Laboratory, Department of Earth and Environmental Science, KSKV Kachchh University, Bhuj-Kachchh, Gujarat, India.

Molecular Ecology and Toxicology Laboratory, Department of Earth and Environmental Science, KSKV Kachchh University, Bhuj-Kachchh, Gujarat, India.

出版信息

Chemosphere. 2020 Feb;241:125076. doi: 10.1016/j.chemosphere.2019.125076. Epub 2019 Oct 13.

DOI:10.1016/j.chemosphere.2019.125076
PMID:31683422
Abstract

Bisphenol A (BPA) is well known as an artificial environmental endocrine disrupting (ED) chemical. BPA also leads to many deleterious impacts on human blood through the production of reactive oxygen species and by some unknown mechanism. Up to now, very few studies have been conducted to assess the impact of BPA on Red Blood Corpuscle (RBC), Complete Blood Count (CBC), and no study on 1HYN (Erythrocyte Band 3 membrane protein) and 1QKI (Human Glucose 6 Phosphate Dehydrogenase) have been so far carried out. Besides, no study has been conducted to assess the ameliorating impact of the most commonly available antioxidant like Gallic Acid (GA). The present investigation revealed that BPA exposure (50-200  μg ml) causes significant increase in percent hemolysis and morphological alteration of RBC, as well as significant reduction in CBC except White Blood Cell (WBC), Platelet, and Red blood density width (RDW). BPA exposure also caused a significant reduction in G6PD activity. In silico docking study revealed that BPA effectively binds with 1HYN and 1QKI protein to alter its activity. Concurrent addition of GA (10-50  μg ml) with highest dose of BPA (200  μg ml) ameliorates all parameters significantly as compared to BPA (200  μg ml) treatment. Ameliorating effect of GA is mainly due to its antioxidant property and interaction with BPA, was confirmed using UV-VIS-NIR Spectrophotometric, molecular dynamic simulation and docking approach by YASARA software.

摘要

双酚 A(BPA)是一种众所周知的人工环境内分泌干扰(ED)化学物质。BPA 还通过产生活性氧物质和一些未知机制对人体血液产生许多有害影响。到目前为止,很少有研究评估 BPA 对红细胞(RBC)、全血细胞计数(CBC)的影响,也没有关于 1HYN(红细胞带 3 膜蛋白)和 1QKI(人葡萄糖 6 磷酸脱氢酶)的研究。此外,也没有研究评估最常用的抗氧化剂如没食子酸(GA)的改善作用。本研究表明,BPA 暴露(50-200μg/ml)会导致红细胞的溶血百分比和形态发生显著变化,除白细胞(WBC)、血小板和红细胞密度宽度(RDW)外,CBC 也显著减少。BPA 暴露还导致 G6PD 活性显著降低。计算机对接研究表明,BPA 能有效地与 1HYN 和 1QKI 蛋白结合,改变其活性。与 BPA(200μg/ml)处理相比,同时添加 GA(10-50μg/ml)最高剂量可显著改善所有参数。GA 的改善作用主要归因于其抗氧化特性及其与 BPA 的相互作用,这一点通过使用 UV-VIS-NIR 分光光度法、分子动力学模拟和 YASARA 软件进行的对接方法得到了证实。

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