Characterization of fluxapyroxad-induced cardiotoxicity in zebrafish

● FLU induces cardiotoxicity in zebrafish at embryonic and adult stages. ● FLU-induced cardiac injury is driven by oxidative stress and mitochondrial dysfunction. ● FLU suppresses mitochondrial complex genes and oxidative phosphorylation. ● FLU disrupts glycolysis and TCA cycle metabolism in the heart. ● FLU shows strong binding affinity to multiple zebrafish SDH subunits. Fluxapyroxad (FLU), a widely detected succinate dehydrogenase inhibitor fungicide, poses potential cardiotoxic risks to aquatic organisms. In this study, we explored the cardiotoxic mechanisms of FLU in zebrafish at both embryonic and adult stages. Embryonic FLU exposure caused significant cardiac structural and functional abnormalities, accompanied by increased reactive oxygen species, elevated malondialdehyde, reduced glutathione, and heightened apoptosis. Ultrastructural analysis revealed mitochondrial vacuolization, matrix rarefaction, and myofibril disorganization. Mitochondrial respiration, including basal respiration, ATP production, and maximal respiration, was significantly suppressed. In adult zebrafish, FLU led to atrial enlargement, ventricular wall thickening, reduced blood flow, and additional mitochondrial damage. Transcriptomic data showed marked downregulation of mitochondrial complex subunit genes and disruptions in oxidative phosphorylation and reactive oxygen species pathways. Metabolomic analysis demonstrated significant alterations in glycolytic and tricarboxylic acid cycle metabolites, reflecting impaired cardiac energy metabolism. Molecular docking further demonstrated strong binding of FLU to zebrafish succinate dehydrogenase subunits, supporting direct inhibition at the protein level. Collectively, these findings reveal that FLU induces cardiotoxicity by promoting oxidative stress, disrupting mitochondrial function, and impairing energy metabolism. This study offers mechanistic insight into SDHI fungicide toxicity and supports their ecological risk assessment. Download: Download high-res image (207KB) Download: Download full-size image