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Role of the Nrf2-ARE pathway in perfluorooctanoic acid (PFOA)-induced hepatotoxicity in Rana nigromaculata
Environmental Pollution ( IF 7.6 ) Pub Date : 2018-02-17 , DOI: 10.1016/j.envpol.2018.02.037
Juan Tang , Xiuying Jia , Nana Gao , Yingzhu Wu , Zhengquan Liu , Xiangjun Lu , Qiongxia Du , Jianbo He , Ning Li , Bin Chen , Jinxiao Jiang , Wenli Liu , Ying Ding , Weiqin Zhu , Hangjun Zhang

Perfluorooctanoic acid (PFOA) is widely distributed in various environmental media and is toxic to organisms. This study demonstrated that PFOA induces hepatotoxicity in the frog and evaluated the role of CYP3A and the Nrf2-ARE signaling pathway in regulating responses to PFOA-induced hepatotoxicity. Rana nigromaculata were exposed to 0, 0.01, 0.1, 0.5, or 1 mg/L PFOA solutions in a static-renewal system for 14 days. Liver tissue samples were collected 24 h after the last treatment. Hepatic histology was observed by HE staining and transmission electron microscopy. The oxidative stress levels in the liver were measured. The expression levels of CYP3A, Nrf2, NQO1, and HO-1 mRNA were measured by quantitative reverse transcription–polymerase chain reaction. PFOA-treated frog liver tissue exhibited diffuse cell borders, cytoplasmic vacuolization, broken nuclei, nuclear chromatin margination, and swollen mitochondria. In addition, the livers of PFOA-treated frogs showed a significantly elevated content of reactive oxygen species, malondialdehyde, glutathione and glutathione S-transferase activity compared to the livers of control frogs. However, the glutathione peroxidase activities concomitantly decreased in PFOA-treated frogs compared to those in the control group. Furthermore, compared with control frogs, the expression levels of CYP3A, Nrf2, and NQO1 mRNA significantly increased in PFOA-treated frogs. HO-1 mRNA expression remarkably increased only in groups treated with 0.5 or 1 mg/L PFOA. Our results indicate that PFOA induces hepatotoxicity in a dose-dependent manner. Furthermore, the results of the comparison analysis between different gender groups illustrated that PFOA is more toxic to female frogs than male frogs. Our results demonstrated that PFOA causes liver damage and that CYP3A enhances PFOA-induced female frogs hepatotoxicity are more virulent than male through biotransformation, and the activation of the Nrf2-ARE pathway is induced to protect against hepatotoxicity in Rana nigromaculata, all of which provide the scientific basis for the protection of amphibians against environmental contaminants.



中文翻译:

Nrf2-ARE途径在全氟辛酸(PFOA)诱导的黑斑蛙肝毒性中的作用

全氟辛酸(PFOA)广泛分布在各种环境介质中,对生物有毒。这项研究表明PFOA诱导青蛙肝毒性,并评估了CYP3A和Nrf2-ARE信号通路在调节对PFOA诱导的肝毒性反应中的作用。黑蛙在静态更新系统中,将其暴露于0、0.01、0.1、0.5或1 mg / L PFOA溶液中14天。最后处理24小时后收集肝组织样品。通过HE染色和透射电镜观察肝组织学。测量肝脏中的氧化应激水平。CYP3A,Nrf2,NQO1和HO-1 mRNA的表达水平通过定量逆转录聚合酶链反应测定。经PFOA处理的蛙肝组织表现出弥漫性细胞边界,胞质空泡,核破裂,核染色质边缘化和线粒体肿胀。此外,用PFOA处理过的青蛙的肝脏中活性氧,丙二醛,谷胱甘肽和谷胱甘肽S的含量显着增加。-转移酶活性与对照青蛙的肝脏相比。但是,与对照组相比,PFOA处理过的青蛙的谷胱甘肽过氧化物酶活性随之降低。此外,与对照青蛙相比,经PFOA处理的青蛙中CYP3A,Nrf2和NQO1 mRNA的表达水平显着增加。HO-1 mRNA表达仅在用0.5或1 mg / L PFOA处理的组中显着增加。我们的结果表明,PFOA以剂量依赖的方式诱导肝毒性。此外,不同性别组之间的比较分析结果表明,PFOA对雌蛙的毒性要大于雄蛙。我们的研究结果表明,PFOA会引起肝脏损害,而CYP3A增强PFOA诱导的雌性青蛙的肝脏毒性比雄性通过生物转化更具毒性,黑林蛙(Rana nigromaculata),所有这些都为保护两栖动物免受环境污染提供了科学依据。

更新日期:2018-02-17
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