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Gender differences in mercury-induced hepatotoxicity: Potential Mechanisms
Chemosphere ( IF 8.8 ) Pub Date : 2018-03-16 , DOI: 10.1016/j.chemosphere.2018.03.106
María Herminia Hazelhoff , Adriana Mónica Torres

The accumulation of mercury in the liver causes hepatotoxicity. The organic anion transporter 3 (Oat3) and the multidrug-resistance associated protein 2 (Mrp2) are involved in the hepatic excretion of toxins and drugs and in the hepatic handling of mercury. The aim of this work was to study if there are gender-related differences in mercuric chloride (HgCl2)-induced hepatotoxicity in rats. Total mercury levels and protein expressions of Oat3 and Mrp2 in liver samples were also assessed to clarify the mechanisms underlying mercury-induced liver damage in male and female rats.

Control and HgCl2-treated male and female Wistar rats were used. Hepatotoxicity was evaluated by plasma activity of transaminases and alkaline phosphatase, as well as by histopathological analysis. Oat3 and Mrp2 expression was assessed by immunoblotting. Female rats displayed a higher HgCl2-induced hepatotoxicity than male rats as demonstrated by the higher alterations in the plasma markers of liver damage and in the histopathology. The sex-related differences observed in the hepatic damage can be explained by the higher accumulation of mercury in liver from female rats. In this connection, after mercury treatment the expression of Mrp2 decreased in both sexes and the expression of Oat3 decreased only in males. The decreased in Oat3 abundance in the hepatocytes membranes in mercury-treated males would limit the uptake of mercuric ions into the liver protecting them from mercury hepatotoxicity.



中文翻译:

汞诱导的肝毒性中的性别差异:潜在机制

汞在肝脏中的积累会引起肝毒性。有机阴离子转运蛋白3(Oat3)和多药耐药相关蛋白2(Mrp2)参与毒素和药物的肝排泄以及肝中汞的处理。这项工作的目的是研究在氯化汞(HgCl 2)诱导的大鼠肝毒性中是否存在性别相关的差异。还评估了肝脏样品中Oat3和Mrp2的总汞水平和蛋白质表达,以阐明汞诱导的雄性和雌性大鼠肝损伤的潜在机制。

使用对照和HgCl 2处理的雄性和雌性Wistar大鼠。通过转氨酶和碱性磷酸酶的血浆活性以及组织病理学分析评估肝毒性。通过免疫印迹评估Oat3和Mrp2的表达。雌性大鼠显示出较高的HgCl 2肝损伤的血浆标志物和组织病理学改变较高,证明了雄性大鼠具有更高的肝毒性。肝损伤中观察到的性别相关差异可以解释为雌性大鼠肝脏中汞含量更高。在这方面,经过汞处理后,男女两性的Mrp2表达均降低,而男性仅有Oat3的表达降低。经汞处理的雄性小鼠肝细胞膜中Oat3丰度的降低将限制汞离子进入肝脏的吸收,从而保护其免受汞肝毒性的影响。

更新日期:2018-03-17
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