Benfuracarb impairs zebrafish swim bladder development via the JNK2 pathway mediated inhibition of autophagy

Abstract

Benfuracarb is widely utilized for crop protection due to its effective pest control properties; however, little information is available regarding its adverse effects and possible molecular mechanisms in fish development. In the present study, benfuracarb exposure caused defects in the development and inflation of the swim bladder, as well as in the lipid metabolism of zebrafish larvae. Compared with the control, key genes involved in swim bladder development, lipid metabolism, surfactant proteins and autophagy were altered in response to benfuracarb exposure. Furthermore, potential targets of benfuracarb were identified using network toxicology and molecular docking, with c-Jun N-terminal kinase 2 (JNK2 encoded by mapk9) predicted as a critical target. Moreover, the JNK family activator anisomycin was observed to mitigate the inhibitory effects of benfuracarb on zebrafish swim bladder inflation, as well as on the expression of autophagy-related genes, suggesting that benfuracarb may inhibit swim bladder development and inflation by downregulating the JNK2 signaling pathway. Overall, this study suggests that the swim bladder might serve as a potential target organ for benfuracarb toxicity in zebrafish, providing valuable insights for assessing the environmental risks of benfuracarb.