Mepanipyrim induces cardiotoxicity of zebrafish(Danio rerio) larvae via promoting AhR-regulated COX expression pathway

作     者：Chao Shen Jing He Kongyang Zhu Naying Zheng Yue Yu Chengyong He Chunyan Yang Zhenghong Zuo Chao Shen;Jing He;Kongyang Zhu;Naying Zheng;Yue Yu;Chengyong He;Chunyan Yang;Zhenghong Zuo

作者机构：State Key Laboratory of Cellular Stress BiologySchool of Life SciencesXiamen UniversityXiamen 361005China State Key Laboratory of Marine Environmental ScienceXiamen UniversityXiamen 361005China 

出 版 物：《Journal of Environmental Sciences》 (环境科学学报（英文版）)

年 卷 期：2023年第125卷第3期

页      面：650-661页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 0713[理学-生态学] 

基　　金：supported by the National Natural Science Foundation of China (Nos. 42177411 and 31971234)。 

主　　题：Zebrafish(Danio rerio) Mepanipyrim AhR agonist Cardiotoxicity CH_(2)23191 Cytochrome coxidase 

摘      要：The wide use of pesticides has seriously threatened human health and the survival of beneficial organisms. The fungicide mepanipyrim is widely used in viticulture practices. Studies of mepanipyrim-induced toxicity in organisms are still scarce, especially studies on cardiotoxicity. In this study, we aimed to investigate mepanipyrim-induced cardiotoxicity in zebrafish(Danio rerio) larvae. We found that mepanipyrim could induce cardiotoxicity by altering the heart rate and cardiomyocyte diameter of larvae. Meanwhile, RNA sequencing and RT-qPCR data indicated that mepanipyrim exposure could dramatically alter the m RNA expression of calcium signaling pathway-, cardiac muscle contraction-, and oxidative respiratory chain-related genes. Interestingly, by the CALUX cell bioassay, we found that most cytochrome c oxidase(COX) family genes exhibited potential AhR-regulated activity, suggesting that mepanipyrim induced cardiotoxicity via a novel AhR-regulated manner in larvae.Additionally, the AhR antagonist CH_(2)23191 could effectively prevent mepanipyrim-induced cardiotoxicity in zebrafish larvae. In conclusion, the AhR agonist mepanipyrim could induce cardiotoxicity in a novel unreported AhR-regulated manner, which could specifically affect the expression of COX family genes involved in the mitochondrial oxidative respiratory chain. Our data will help explain the toxic effects of mepanipyrim on organisms and provide new insight into the AhR agonistic activity pesticide-induced cardiotoxicity.