谷胱甘肽
GPX4
线粒体
丙二醛
活性氧
毒物
化学
药理学
氧化应激
生物
生物化学
毒性
酶
谷胱甘肽过氧化物酶
有机化学
作者
Ling Wei,Zhuang Zuo,Ziyuan Yang,Heng Yin,Yue Yang,Jing Fang,Hengmin Cui,Zongjun Du,Ping Ouyang,Xia Chen,Jian Chen,Yi Geng,Yanqiu Zhu,Zhengli Chen,Chao Huang,Fengyuan Wang,Hongrui Guo
出处
期刊:Toxicology
[Elsevier]
日期:2022-01-01
卷期号:466: 153068-153068
被引量:29
标识
DOI:10.1016/j.tox.2021.153068
摘要
Nickel (Ni) is an environmental toxicant that can cause toxic damage to humans and animals. Although the hepatotoxicity of Ni has been confirmed, its precise mechanism is still unclear. In this study, the results showed that nickel chloride (NiCl2)-treatment could induce mice hepatotoxicity including hepatic histopathological alterations and up-regulation of serum AST and ALT. According to the results, NiCl2 increased malondialdehyde (MDA) production while reducing total antioxidant capacity (T-AOC) activity and glutathione (GSH) content. Additionally, NiCl2 induced mitochondrial damage which was featured by increase in mitochondrial ROS (mt-ROS) and mitochondrial membrane potential (MMP) depolarization. The mitochondrial respiratory chain complexes I-IV and ATP content were decreased in the liver of NiCl2-treated mice. Meanwhile, NiCl2 caused hepatic ferroptosis accompanied by increased iron content in the liver and up-regulation of cyclooxygenase 2 (COX-2) protein and mRNA expression levels, down-regulation of glutathione eroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1) and nuclear receptor coactivator 4 (NCOA4) protein and mRNA expression levels. Altogether, the above mentioned results indicate that NiCl2 treatment may induce hepatic damage through mitochondrial damage and ferroptosis.
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