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Stereoselective cardiotoxic effects of metconazole on zebrafish (Danio rerio) based on AGE-RAGE signalling pathway

文献类型： 外文期刊

作者： Li, Minmin 1 ; Yang, Lin 2 ; Wang, Rui 1 ; Li, Lin 1 ; Zhang, Yifan 1 ; Li, Long 1 ; Jin, Nuo 1 ; Huang, Yatao 1 ; Kong, Zhiqiang 3 ; Francis, Frederic 4 ; Fan, Bei 1 ; Wang, Fengzhong 1 ;

作者机构： 1.Chinese Acad Agr Sci, Inst Food Sci & Technol, Key Lab Agroprod Qual & Safety Control Storage & T, Minist Agr & Rural Affairs,Lab Agroprod Qual Safet, Beijing 100093, Peoples R China

2.Guizhou Univ, Ctr Res & Dev Fine Chem, Natl Key Lab Green Pesticide, Key Lab Green Pesticide & Agr Bioengn,Minist Educ, Guiyang 550025, Peoples R China

3.Chinese Acad Agr Sci, Inst Plant Protect, State Key Lab Biol Plant Dis & Insect Pests, Beijing 100193, Peoples R China

4.Univ Liege, Funct & Evolutionary Entomol, Gembloux Agrobiotech, Passage Deportes 2, B-5030 Gembloux, Belgium

关键词： Metconazole; Chiral pesticides; Zebrafish embryo; Stereoselective cardiotoxicity; p38 inhibitor

期刊名称：SCIENCE OF THE TOTAL ENVIRONMENT （ 影响因子：9.8； 五年影响因子：9.6 ）

ISSN： 0048-9697

年卷期： 2024 年 912 卷

页码：

收录情况： SCI

摘要： Metconazole (MEZ) is a novel chiral triazole fungicide that is widely used to prevent and control soil-borne fungal pathogens and other fungal diseases. However, it has a long half-life in aquatic environments and thus poses potential environmental risks. This study evaluates the acute and stereoselective cardiotoxicity of MEZ in zebrafish (Danio rerio) embryos. In addition, transcriptomics, real-time quantitative PCR, enzyme activity determination, and molecular docking are performed to evaluate the molecular mechanisms underlying the cardiotoxicity of MEZ in zebrafish. MEZ decreases the heart rate while increasing the pericardial oedema rate; additionally, it induces stereoselective cardiotoxicity. 1S,5S-MEZ exhibits stronger cardiotoxicity than 1R,5RMEZ. Furthermore, MEZ increases the expression of Ahr-associated genes and the transcription factors il6st, il1b, and AP-1. Heart development-related genes, including fbn2b, rbm24b, and tbx20 are differentially expressed. MEZ administration alters the activities of catalase, peroxidase, and glutathione-S-transferase in zebrafish larvae. Molecular docking indicates that 1R,5R-MEZ binds more strongly to the inhibitor-binding sites of p38 in the AGE-RAGE signalling pathway than to other MEZ enantiomers. Studies conducted in vivo and in silico have established the enantioselective cardiotoxicity of MEZ and its underlying mechanisms, highlighting the need to evaluate the environmental risk of chiral MEZ in aquatic organisms at the enantiomeric level.

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