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

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Journal of Environmental Sciences 2023年第3期125卷 650-661页

作者： Chao Shen Jing He Kongyang Zhu Naying Zheng Yue Yu Chengyong He Chunyan Yang Zhenghong Zuo State Key Laboratory of Cellular Stress Biology School of Life SciencesXiamen UniversityXiamen 361005China State Key Laboratory of Marine Environmental Science Xiamen UniversityXiamen 361005China

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.

关键词： Zebrafish(Danio rerio) Mepanipyrim AhR agonist Cardiotoxicity CH_(2)23191 Cytochrome coxidase

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Mepanipyrim induces visual developmental toxicity and vision-guided behavioral alteration in zebrafish larvae

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Journal of Environmental Sciences 2023年第2期124卷 76-88页

作者： Chao Shen Yimei Cai Jialing Li Chengyong He Zhenghong Zuo State Key Laboratory of Cellular Stress Biology School of Life SciencesXiamen UniversityXiamen 361005China State Key Laboratory of Marine Environmental Science Xiamen UniversityXiamen 361005China

Mepanipyrim,an anilinopyrimidine fungicide,has been extensively used to prevent fungal diseases in fruit culture.Currently,research on Mepanipyrim-induced toxicity in organisms is still very scarce,especially visual developmental toxicity.Here,zebrafish larvae were employed to investigate Mepanipyrim-induced visual developmental toxicity.Intense light andmonochromatic light stimuli-evoked escape experiments were used to investigate vision-guided behaviors.Meanwhile,transcriptomic sequencing and real-time quantitative PCR assays were applied to assess the potential mechanisms of Mepanipyrim-induced visual developmental toxicity and vision-guided behavioral alteration.Our results showed that Mepanipyrim exposure could induce retinal impairment and vision-guided behavioral alteration in larval zebrafish.In addition,the grk1b gene of the phototransduction signaling pathway was found to be a potential aryl hydrocarbon receptor(AhR)-regulated gene.Mepanipyrim-induced visual developmental toxicity was potentially related to the AhR signaling pathway.Furthermore,Mepanipyrim-induced behavioral alteration was guided by the visual function,and the effects of Mepanipyrim on long and middle wavelength light-sensitive opsins may be the main cause of vision-guided behavioral alteration.Our results provide insights into understanding the relationship between visual development and vision-guided behaviors induced by Mepanipyrim exposure.

关键词： Danio rerio Mepanipyrim visual developmental toxicity vision-guided behaviors phototransduction signaling pathway grk1b

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