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

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 exp...

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Main Authors: Jiawen Cui, Zhiyu Hao, Qin Zhou, Minna Qiu, Yuhang Liu, Yuhao Liu, Xiaohua Teng, Lu Kang
Format: Article
Language:English
Published: Elsevier 2023-06-01
Series:Ecotoxicology and Environmental Safety
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0147651323004876
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author Jiawen Cui
Zhiyu Hao
Qin Zhou
Minna Qiu
Yuhang Liu
Yuhao Liu
Xiaohua Teng
Lu Kang
author_facet Jiawen Cui
Zhiyu Hao
Qin Zhou
Minna Qiu
Yuhang Liu
Yuhao Liu
Xiaohua Teng
Lu Kang
author_sort Jiawen Cui
collection DOAJ
description 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 further contributed to the induction of mitophagy and autophagy. Subsequently, we confirmed a time-dependent hepatotoxicity caused by CPF in common carp via IBR assessment. Our findings presented a new insight into molecular mechanism of CPF induced-hepatotoxicity in common carp, and provided a theoretical basis for evaluating CPF toxicity to aquatic organisms.
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spelling doaj.art-0e8f1e232195493db7d649c239ae22222023-05-20T04:29:07ZengElsevierEcotoxicology and Environmental Safety0147-65132023-06-01258114983Chlorpyrifos induced autophagy and mitophagy in common carp livers through AMPK pathway activated by energy metabolism disorderJiawen Cui0Zhiyu Hao1Qin Zhou2Minna Qiu3Yuhang Liu4Yuhao Liu5Xiaohua Teng6Lu Kang7College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, People’s Republic of ChinaCollege of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, People’s Republic of ChinaCollege of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, People’s Republic of ChinaCollege of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, People’s Republic of ChinaCollege of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, People’s Republic of ChinaCollege of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, People’s Republic of China; Corresponding authors.College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, People’s Republic of China; Corresponding authors.Institute of Agricultural Quality Standards and Testing Technology, Xinjiang Academy of Agricultural Sciences, Urumqi 830091, People’s Republic of China; Corresponding authors.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 further contributed to the induction of mitophagy and autophagy. Subsequently, we confirmed a time-dependent hepatotoxicity caused by CPF in common carp via IBR assessment. Our findings presented a new insight into molecular mechanism of CPF induced-hepatotoxicity in common carp, and provided a theoretical basis for evaluating CPF toxicity to aquatic organisms.http://www.sciencedirect.com/science/article/pii/S0147651323004876ChlorpyrifosMitophagyAutophagyOxidative stressGlucose metabolismIBR
spellingShingle Jiawen Cui
Zhiyu Hao
Qin Zhou
Minna Qiu
Yuhang Liu
Yuhao Liu
Xiaohua Teng
Lu Kang
Chlorpyrifos induced autophagy and mitophagy in common carp livers through AMPK pathway activated by energy metabolism disorder
Ecotoxicology and Environmental Safety
Chlorpyrifos
Mitophagy
Autophagy
Oxidative stress
Glucose metabolism
IBR
title Chlorpyrifos induced autophagy and mitophagy in common carp livers through AMPK pathway activated by energy metabolism disorder
title_full Chlorpyrifos induced autophagy and mitophagy in common carp livers through AMPK pathway activated by energy metabolism disorder
title_fullStr Chlorpyrifos induced autophagy and mitophagy in common carp livers through AMPK pathway activated by energy metabolism disorder
title_full_unstemmed Chlorpyrifos induced autophagy and mitophagy in common carp livers through AMPK pathway activated by energy metabolism disorder
title_short Chlorpyrifos induced autophagy and mitophagy in common carp livers through AMPK pathway activated by energy metabolism disorder
title_sort chlorpyrifos induced autophagy and mitophagy in common carp livers through ampk pathway activated by energy metabolism disorder
topic Chlorpyrifos
Mitophagy
Autophagy
Oxidative stress
Glucose metabolism
IBR
url http://www.sciencedirect.com/science/article/pii/S0147651323004876
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