Multi-organ toxicity via oxidative stress and disrupting mitochondrial plasticity induced by bendiocarb in zebrafish.

Bendiocarb, a carbamate insecticide, is widely applied in various circumstances; however, it poses a potential threat to various non-target organisms. Although many researchers have focused on defining the toxic effects of bendiocarb, those associated with early and organ development remain poorly understood. In this study, we evaluated the developmental and organ-specific toxic mechanisms of bendiocarb in a zebrafish model. Exposure of bendiocarb decreased viability of zebrafish larvae by changing morphology and inducing production of reactive oxygen species with a decrease of the expression of antioxidant genes cat and sod2. In addition, bendiocarb affected mitochondrial bioenergetics and plasticity with reduction of mitochondrial complexes I, III, and V related genes leading to suppression of ATP generation. To investigate multi-organ toxic effects of bendiocarb, various transgenic zebrafish were utilized, for example, cardiac toxicity, impaired vasculature, and interfered blood flow were confirmed using cmlc2:dsRed, fli1a:EGFP, and gata1a:dsRed. Hepatotoxicity was examined using the fabp10a:dsRed model, and pancreatic toxicity was elucidated using the elastase:EGFP and insulin:EGFP models. Additionally, abnormal neuronal development was observed following treatment with olig2:dsRed and gad1b:EGFP. Moreover, changes at the molecular level by whole mount in situ hybridization and qPCR analyses were consistent with our observations. Furthermore, N-acetylcysteine (NAC) co-treatment substantially ameliorated developmental toxicity across multiple organ systems, including the cardiovascular, metabolic, and nervous systems. Taken together, this study provides novel perspectives on the system-level toxicity of bendiocarb and its molecular mechanisms of action in zebrafish.