Perfluorooctane sulphonate induces oxidative hepatic damage via mitochondria-dependent and NF-κB/TNF-α-mediated pathway
Perfluorooctane sulphonate induces oxidative hepatic damage via mitochondria-dependent and NF-κB/TNF-α-mediated pathway
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全氟辛烷磺酸通过线粒体依赖性和 NF-κB/TNF-α 介导的途径诱导氧化性肝损伤
DOI：
10.1016/j.chemosphere.2017.08.070
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发表时间：
2018-01-01
期刊：
影响因子：
8.8
通讯作者：
Ding, Wenjun
中科院分区：
文献类型：
--
作者：
Han, Rui;Hu, Mingxian;Ding, Wenjun
据报道，全氟辛烷磺酸（PFOS）可在肝脏中积聚并造成损害。全氟辛烷磺酸引起肝毒性的分子机制尚未完全阐明。本研究旨在探讨全氟辛烷磺酸诱导的氧化应激是否在肝损伤中起重要作用，如果起重要作用，其毒理学作用的机制经过哪些途径。雄性SD大鼠按1或10 mg/kg体重单剂量口服全氟辛烷磺酸，连续28天。全氟辛烷磺酸暴露大鼠血清肝酶水平升高，超结构改变异常。特别是，全氟辛烷磺酸暴露显著增加了细胞内活性氧（ROS）和一氧化氮（NO）的产生，但通过抑制过氧化氢酶和超氧化物歧化酶活性削弱了细胞内抗氧化防御。信号转导研究表明，PFOS暴露显著升高诱导型一氧化氮合酶（iNOS）、Bax、细胞色素c、cleaved caspase-9和cleaved caspase-3，表明线粒体依赖性凋亡途径被激活。另一方面，pfos诱导的NF-kappa B和I -kappa B α蛋白表达显著改变，与tnf - α水平升高相关。综上所述，这些结果表明线粒体在全氟辛烷磺酸诱导的肝毒性中起重要作用。(C) 2017年Elsevier Ltd.出版
Perfluorooctane sulphonate (PFOS) has been reported to accumulate in liver and cause damage. The molecular mechanism of the PFOS-induced hepatotoxicity has not been completely elucidated. The aim of the present study was to investigate whether PFOS-induced oxidative stress plays an important role in liver damage, and if so, what pathway it undergoes for the mechanism of its toxicological action. Male Sprague-Dawley (SD) rats were orally administrated with PFOS at single dose of I or 10 mg/kg body weight for 28 consecutive days. Increased serum levels of liver enzymes and abnormal ultra structural changes were observed in the PFOS-exposed rats. Particularly, PFOS exposure significantly increased intracellular reactive oxygen species (ROS) and nitric oxide (NO) production, but weakened intracellular antioxidant defence by inhibiting catalase and superoxide dismutase activities. Signal transduction studies showed that PFOS exposure significantly elevated inducible nitric oxide synthase (iNOS), Bax, cytochrome c, cleaved caspase-9 and cleaved caspase-3, indicating the mitochondria-dependent apoptotic pathway was activated. On the other hand, significant alterations of the PFOS-induced protein expression of NF-kappa B and I kappa B alpha in association with an enhanced level of TNF-alpha were observed. Taken together, these results indicate that mitochondria play an important role in PFOS-induced hepatotoxicity. (C) 2017 Published by Elsevier Ltd.