Complementary biological and computational approaches identify distinct mechanisms of chlorpyrifos versus chlorpyrifos-oxon-induced dopaminergic neurotoxicity.

ABSTRACT: Organophosphate (OP) pesticides are widely used in agriculture. While acute cholinergic toxicity has been extensively studied, chronic effects on other neurons are less understood. Here, we demonstrated that the OP pesticide chlorpyrifos (CPF) and its oxon metabolite are dopaminergic neurotoxicants in Caenorhabditis elegans. CPF treatment led to inhibition of mitochondrial complex II, II + III, and V in rat liver mitochondria, while CPF-oxon did not (complex II + III and IV inhibition observed only at high doses). While the effect on C. elegans cholinergic behavior was mostly reversible with toxicant washout, dopamine-associated deficits persisted, suggesting dopaminergic neurotoxicity was irreversible. CPF reduced the mitochondrial content in a dose-dependent manner and the fat modulatory

SUBMITTER: Sammi SR 

PROVIDER: S-EPMC9887671 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature