Stereo-selective cardiac toxicity induced by metconazole via oxidative stress and the wnt/β-catenin signaling pathway in zebrafish embryos

文献类型： 外文期刊

第一作者： Liu, Lulu

作者： Liu, Lulu;Wang, Fengzhong;Fan, Bei;Li, Lin;Zhang, Yifan;Yan, Zhihui;Li, Minmin;Liu, Lulu;Zhang, Zhong;Luo, Ying;Kong, Zhiqiang;Francis, Frederic

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关键词： cis -Metconazole; Zebrafish; Stereoselective cardiotoxicity; Oxidative stress; Wnt/ss-catenin signaling pathway

期刊名称：ENVIRONMENTAL POLLUTION （ 影响因子：8.9； 五年影响因子：9.5 ）

ISSN： 0269-7491

年卷期： 2024 年 350 卷

页码：

收录情况： SCI

摘要： Metconazole (MEZ), a chiral triazole fungicide, produces enantioselective adverse effects in non-target organisms. Among MEZ's isomers, cis-MEZ displays robust antimicrobial properties. Evaluating MEZ and cis-MEZ's toxicity may mitigate fungicide usage and safeguard non-target organisms. Our study evaluated the toxicity of MEZ and its cis-isomers at concentrations of 0.02, 0.2, 2, and 4 mg L-1. We report stereoselectivity and severe cardiovascular defects in zebrafish, including pericardial oedema, decreased heart rate, increased sinus venous and bulbous arteries distances, intersegmental vessel defects, and altered cardiovascular development genes (hand2, gata4, nkx2.5, tbx5, vmhc, amhc, dll4, vegfaa, and vegfc). Further, MEZ significantly increased oxidative stress and apoptosis in zebrafish, primarily in the cardiac region. Isoquercetin, an antioxidant found in plants, partially mitigates MEZ-induced cardiac defects. Furthermore, MEZ upregulated the Wnt/ss-catenin pathway genes (wnt3, ss-catenin, axin2, and gsk-3 ss) and ss-catenin protein expression. Inhibitor of Wnt Response-1 (IWR-1) rescued MEZ-induced cardiotoxicity. Our findings highlight oxidative stress, altered cardiovascular development genes, and upregulated Wnt/ss-catenin signaling as contributors to cardiovascular toxicity in response to MEZ and cis-MEZ treatments. Importantly, 1R,5S-MEZ exhibited greater cardiotoxicity than 1S,5R-MEZ. Thus, our study provides a comprehensive understanding of cis-MEZ's cardiovascular toxicity in aquatic life.

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