Exposure to Oxadiazon-Butachlor causes cardiac toxicity in zebrafish embryos. (October 2020) - Huang, Yong
Abstract: Oxadiazon-Butachlor (OB) is a widely used herbicide for controlling most annual weeds in rice fields. However, its potential toxicity in aquatic organisms has not been evaluated so far. We used the zebrafish embryo model to assess the toxicity of OB, and found that it affected early cardiac development and caused extensive cardiac damage. Mechanistically, OB significantly increased oxidative stress in the embryos by inhibiting antioxidant enzymes that resulted in excessive production of reactive oxygen species (ROS), eventually leading to cardiomyocyte apoptosis. In addition, OB also inhibited the WNT signaling pathway and downregulated its target genes including lef1, axin2 and β-catenin . Reactivation of this pathway by the Wnt activator BML-284 and the antioxidant astaxanthin rescued the embryos form the cardiotoxic effects of OB, indicating that oxidative stress, and inhibition of WNT target genes are the mechanistic basis of OB-induced damage in zebrafish. Our study shows that OB exposure causes cardiotoxicity in zebrafish embryos and may be potentially toxic to other aquatic life and even humans. Graphical abstract: Image 1 Highlights: Oxadiazon-butachlor affects early cardiac development in zebrafish, causing cardiac damage and cardiotoxicity. Exposed to oxadiazon-butachlor increases oxidative stress and induces cell apoptosis in zebrafish heart. The antioxidant astaxanthin can rescue the phenotype caused by oxadiazon-butachlor exposure. Activation of Wnt signaling rescued cardiac defects induced by oxadiazon-butachlor.