Effects of pesticide dichlorvos on liver injury in rats and related toxicity mechanisms
Dichlorvos (DDVP) is an organophosphorus pesticide commonly utilized in agricultural production. Recent epidemiological studies suggest that exposure to DDVP correlates with an increased incidence of liver disease. However, data regarding the hepatotoxicity of DDVP remain limited. Additionally, the...
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Elsevier
2025-01-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325000831 |
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| author | Pengcheng Zhang Zixian Zhou Jiaqi Yao Yuhong Jiang Hang Lei Zhijun Xie Juan Li Xianlin Zhao Lv Zhu Meihua Wan Ling Liu Wenfu Tang |
| author_facet | Pengcheng Zhang Zixian Zhou Jiaqi Yao Yuhong Jiang Hang Lei Zhijun Xie Juan Li Xianlin Zhao Lv Zhu Meihua Wan Ling Liu Wenfu Tang |
| author_sort | Pengcheng Zhang |
| collection | DOAJ |
| description | Dichlorvos (DDVP) is an organophosphorus pesticide commonly utilized in agricultural production. Recent epidemiological studies suggest that exposure to DDVP correlates with an increased incidence of liver disease. However, data regarding the hepatotoxicity of DDVP remain limited. Additionally, the regulatory mechanisms underlying DDVP-induced liver injury have not been thoroughly investigated. In this study, we utilized Wistar rats and BRL-3A cells to establish in vivo and in vitro models for examining the effects of DDVP exposure on liver damage. Our findings indicate that DDVP impairs hepatocyte autophagy and increases ROS activity. RNA sequencing and metabolomic analyses revealed that the pathways affected by DDVP exposure in hepatocytes include ABC transporters and amino acid biosynthesis processes. Furthermore, targeting IRGM overexpression through hepatic portal vein injection of adeno-associated virus mitigated DDVP-induced liver injury. These results demonstrate that DDVP exposure induces liver damage in rats through mechanisms that are dependent on ROS and autophagy, at least in part by downregulating IRGM. Our study offers new insights into the molecular mechanisms of liver injury following organophosphate poisoning and suggests that IRGM may represent a novel therapeutic target for DDVP-induced liver injury. |
| format | Article |
| id | doaj-art-853e045c9cc34c1a81ea2b4f7a054188 |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-853e045c9cc34c1a81ea2b4f7a0541882025-02-12T05:30:11ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01290117747Effects of pesticide dichlorvos on liver injury in rats and related toxicity mechanismsPengcheng Zhang0Zixian Zhou1Jiaqi Yao2Yuhong Jiang3Hang Lei4Zhijun Xie5Juan Li6Xianlin Zhao7Lv Zhu8Meihua Wan9Ling Liu10Wenfu Tang11West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China; Regenerative Medicine Research Center, Sichuan University West China Hospital, Chengdu, Sichuan 610041, ChinaDepartment of Neurology, West China Hospital, Sichuan University, Chengdu 610041, ChinaWest China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, ChinaWest China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, ChinaWest China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, ChinaDepartment of Spleen and Stomach Diseases, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Lu zhou, Sichuan 646000, ChinaWest China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, ChinaWest China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, ChinaWest China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, ChinaWest China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, ChinaDepartment of Neurology, West China Hospital, Sichuan University, Chengdu 610041, ChinaWest China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China; Regenerative Medicine Research Center, Sichuan University West China Hospital, Chengdu, Sichuan 610041, China; Correspondence to: 37 Guoxue Lane, Wuhou District, Chengdu, Sichuan, China.Dichlorvos (DDVP) is an organophosphorus pesticide commonly utilized in agricultural production. Recent epidemiological studies suggest that exposure to DDVP correlates with an increased incidence of liver disease. However, data regarding the hepatotoxicity of DDVP remain limited. Additionally, the regulatory mechanisms underlying DDVP-induced liver injury have not been thoroughly investigated. In this study, we utilized Wistar rats and BRL-3A cells to establish in vivo and in vitro models for examining the effects of DDVP exposure on liver damage. Our findings indicate that DDVP impairs hepatocyte autophagy and increases ROS activity. RNA sequencing and metabolomic analyses revealed that the pathways affected by DDVP exposure in hepatocytes include ABC transporters and amino acid biosynthesis processes. Furthermore, targeting IRGM overexpression through hepatic portal vein injection of adeno-associated virus mitigated DDVP-induced liver injury. These results demonstrate that DDVP exposure induces liver damage in rats through mechanisms that are dependent on ROS and autophagy, at least in part by downregulating IRGM. Our study offers new insights into the molecular mechanisms of liver injury following organophosphate poisoning and suggests that IRGM may represent a novel therapeutic target for DDVP-induced liver injury.http://www.sciencedirect.com/science/article/pii/S0147651325000831DichlorvosLiver damageIRGMIncomplete autophagyApoptosisFerroptosis |
| spellingShingle | Pengcheng Zhang Zixian Zhou Jiaqi Yao Yuhong Jiang Hang Lei Zhijun Xie Juan Li Xianlin Zhao Lv Zhu Meihua Wan Ling Liu Wenfu Tang Effects of pesticide dichlorvos on liver injury in rats and related toxicity mechanisms Ecotoxicology and Environmental Safety Dichlorvos Liver damage IRGM Incomplete autophagy Apoptosis Ferroptosis |
| title | Effects of pesticide dichlorvos on liver injury in rats and related toxicity mechanisms |
| title_full | Effects of pesticide dichlorvos on liver injury in rats and related toxicity mechanisms |
| title_fullStr | Effects of pesticide dichlorvos on liver injury in rats and related toxicity mechanisms |
| title_full_unstemmed | Effects of pesticide dichlorvos on liver injury in rats and related toxicity mechanisms |
| title_short | Effects of pesticide dichlorvos on liver injury in rats and related toxicity mechanisms |
| title_sort | effects of pesticide dichlorvos on liver injury in rats and related toxicity mechanisms |
| topic | Dichlorvos Liver damage IRGM Incomplete autophagy Apoptosis Ferroptosis |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325000831 |
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