Developmental hepatotoxicity and lipid metabolic disruption induced by fluxapyroxad in zebrafish embryos: An integrative omics approach.

Fluxapyroxad (FLU), a widely used succinate dehydrogenase inhibitor (SDHI) fungicide, poses increasing environmental and aquatic pollution concerns, yet its hepatotoxic effects during early development remain unclear. This study investigated the developmental hepatotoxicity of FLU in zebrafish embryos exposed to graded concentrations (0.3, 0.6, and 0.9 mg/L) from 72 to 144 h post fertilization (hpf). Results showed significant, concentration-dependent reductions in liver size and yolk sac absorption. Histological analysis confirmed hepatic vacuolization, decreased glycogen deposition, and elevated total cholesterol (T-CHO) and triacylglycerol (TG) levels. Transcriptomic profiling revealed suppressed expression of multiple lipid metabolism-related genes, indicating widespread hepatic lipid dysregulation. Lipidomic analysis identified significant alterations in numerous lipid metabolites, particularly phosphatidylcholine (PC) subclasses. Integrated analysis pinpointed sphingolipid metabolism and glycerophospholipid metabolism as critically disrupted pathways, with most genes and metabolites within these pathways markedly downregulated. Collectively, this study provides novel insights into the lipid metabolic disruptions underlying FLU-induced developmental hepatotoxicity, enhancing our understanding of FLU's toxicological mechanisms and informing biomarker discovery and risk assessment strategies for SDHI fungicides.