Chlorpyrifos induced autophagy and mitophagy in common carp livers through AMPK pathway activated by energy metabolism disorder

作者：Jiawen Cui, Zhiyu Hao, Qin Zhou, Minna Qiu, Yuhang Liu, Yuhang Liu, Yuhao Liu, Yuhao Liu, Xiaohua Teng, Lu Kang · 发表于：Ecotoxicology and Environmental Safety · 年份：2023 · DOI：10.1016/j.ecoenv.2023.114983 · 被引用次数：50 · 研究领域：Environmental Toxicology and Ecotoxicology、Pesticide Exposure and Toxicity、Pesticide and Herbicide Environmental Studies

Water pollution caused by widely used agricultural pesticide chlorpyrifos (CPF) has aroused extensive public concern. While previous studies have reported on toxic effect of CPF on aquatic animal, little is known about its effect on common carp (Cyprinus carpio L.) livers. In this experiment, we exposed common carp to CPF (11.6 μg/L) for 15, 30, and 45 days to establish a poisoning model. Histological observation, biochemical assay, quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, and integrated biomarker response (IBR) were applied to assess the hepatotoxicity of CPF in common carp. Our results displayed that CPF exposure damaged histostructural integrity and induced liver injury in common carp. Furthermore, we found that CPF-induced liver injury may be associated with mitochondrial dysfunction and autophagy, as evidenced by swollen mitochondria, broken mitochondrial ridges, and increased the number of autophagosomes. Moreover, CPF exposure decreased the activities of ATPase (Na+/K+-ATPase, Ca2+-ATPase, Mg2+-ATPase, and Ca2+Mg2+-ATPase), altered glucose metabolism-related genes (GCK, PCK2, PHKB, GYS2, PGM1, and DLAT), and activated energy-sensing AMPK, indicating that CPF caused energy metabolism disorder. The activation of AMPK further induced mitophagy via AMPK/Drp1 pathway, and induced autophagy via AMPK/mTOR pathway. Additionally, we found that CPF induced oxidative stress (abnormal levels of SOD, GSH, MDA, and H2O2) in common carp livers, which ...