Han Rui, Hu Mingxian, Zhong Qiang, Wan Chong, Liu Limin, Li Fang, Zhang Fang, Ding Wenjun
Laboratory of Environment and Health, College of Life Sciences, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.
Department of Pediatrics, Ankang City Central Hospital, No. 85 Jinzhou Road, Ankang 725000, China.
Chemosphere. 2018 Jan;191:1056-1064. doi: 10.1016/j.chemosphere.2017.08.070. Epub 2017 Aug 15.
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 1 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-κB and IκBα in association with an enhanced level of TNF-α were observed. Taken together, these results indicate that mitochondria play an important role in PFOS-induced hepatotoxicity.
据报道，全氟辛烷磺酸（PFOS）会在肝脏中蓄积并造成损害。PFOS诱导肝毒性的分子机制尚未完全阐明。本研究的目的是调查PFOS诱导的氧化应激是否在肝损伤中起重要作用，如果是，其毒理学作用机制通过何种途径发生。将雄性Sprague-Dawley（SD）大鼠连续28天口服给予单剂量1或10 mg/kg体重的PFOS。在暴露于PFOS的大鼠中观察到血清肝酶水平升高和超微结构异常变化。特别是，PFOS暴露显著增加细胞内活性氧（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、裂解的半胱天冬酶-9和裂解的半胱天冬酶-3，表明线粒体依赖性凋亡途径被激活。另一方面，观察到PFOS诱导的NF-κB和IκBα蛋白表达与TNF-α水平升高相关的显著变化。综上所述，这些结果表明线粒体在PFOS诱导的肝毒性中起重要作用。
