Comprehensive assessment of fenpropathrin on the health of non-target organisms: Integrating in vivo, in vitro, and in silico methodologies.

Despite the widespread detection of fenpropathrin (FEN), a synthetic pyrethroid insecticide, in aquatic ecosystems, the toxic effects on non-target organisms and the associated environmental health risks remain inadequately characterized. In this study, the adverse effects and underlying mechanisms of FEN on zebrafish liver were investigated using in vivo, in vitro, and in silico approaches. Zebrafish were exposed to FEN at concentrations of 0.45 and 1.35 μg/L for 28 days, resulting in pathological injury and lipid accumulation in the liver, along with significant alterations in the expression of carbohydrate and lipid metabolism-related indicators. Furthermore, exposure to FEN resulted in the upregulation of reactive oxygen species (ROS) and malondialdehyde levels, triggered apoptosis, and was associated with a significant increase in caspase-3 levels. Additionally, FEN induced cell cycle arrest, a decrease in mitochondrial membrane potential, excessive production of ROS, leading to lipid accumulation and apoptosis in zebrafish liver (ZFL) cells, suggesting that FEN can elicit hepatocyte toxicity. RNA-Seq analysis of ZFL cells further demonstrated that FEN modulates key pathways associated with cell cycle regulation, apoptosis, and metabolic processes. Molecular docking results indicated that pck2 might serve as a potential target for FEN-induced hepatotoxicity. Collectively, this study elucidated the hepatotoxic effects and underlying mechanisms of FEN in zebrafish, thereby enhancing our understanding of the non-target biotoxicity associated with FEN and offering novel insights into its potential environmental health risks.