Arsenic causes mitochondrial biogenesis obstacles by inhibiting the AMPK/PGC-1 alpha signaling pathway and also induces apoptosis and dysregulated mitophagy in the duck liver
文献类型： 外文期刊
第一作者： Zhong, Gaolong
作者： Zhong, Gaolong;Hu, Ting;Tang, Lixuan;Li, Tong;Wu, Shaofeng;Pan, Jiaqiang;Zhang, Hui;Tang, Zhaoxin;Hu, Lianmei;Duan, Xuewu;Feng, Xia;Duan, Xuewu
作者机构：
关键词： Duck; Arsenic; Mitochondrial biogenesis; Apoptosis; Mitophagy
期刊名称：ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY （ 影响因子：7.129； 五年影响因子：7.284 ）
ISSN： 0147-6513
年卷期： 2022 年 230 卷
页码：
收录情况： SCI
摘要： Arsenic is a dangerous metalloid-material which is known to cause liver injury in many animals and humans. However, little is known about the underlying mechanism of arsenic-induced hepatotoxicity in poultry. This study was executed to systematically investigate the potential role of mitochondrial biogenesis, mitophagy and apoptosis in duck hepatotoxicity caused by arsenic. Results showed that the body weight and liver coefficient of duck had distinct changed after arsenic-exposure, and the arsenic content in serum and liver also increased significantly in a dose-dependent manner. Meanwhile, histopathological examination and metabolomics results showed that arsenic-exposure caused severe steatosis and metabolism disorder in liver tissues. Furthermore, arsenic-exposure significantly inhibited AMPK/PGC-1 alpha-mediated mitochondrial biogenesis, determined by the ultrastructure observation and down-regulation of p-AMPK alpha/AMPK alpha, PGC-1 alpha, NRF1, NRF2, TFAM, TFB1M, TFB2M and COX-IV expression levels. Besides, arsenic-treatment obviously increased the levels of mitophagy (PINK1, Parkin, LC3, P62) and pro-apoptotic (Caspase-3, Caspase-9, Cleaved Caspase-3, Cytc, Bax, P53) indexes, and simultaneously resulted in reductions in anti-apoptosis index (Bcl-2). Overall, our findings provided evidences that arsenic-induced duck hepatotoxicity may be caused by a combination of impaired mitochondrial biosynthesis, mitophagy, and mitochondrial-dependent apoptosis. To our knowledge, this is the first report to systematically investigate the potential mechanism of arsenic-induced hepatotoxicity in poultry.
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