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

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/β-catenin pathway genes (wnt3, β-catenin, axin2, and gsk-3β) and β-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/β-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.PMID:38663507 | DOI:10.1016/j.envpol.2024.124034

Source: Environmental Pollution - April 25, 2024 Category: Environmental Health Authors: Lulu Liu Fengzhong Wang Zhong Zhang Bei Fan Ying Luo Lin Li Yifan Zhang Zhihui Yan Zhiqiang Kong Fr édéric Francis Minmin Li Source Type: research