Performance of a novel atrazine-induced cerebellar toxicity in quail (Coturnix C. coturnix): Activating PXR/CAR pathway responses and disrupting cytochrome P450 homeostasis.

Atrazine is well known to be a biologically hazardous substance with toxic effects, but atrazine-induced neurotoxicity remains unclear. The aim of this study was to investigate the mechanisms of atrazine-induced cerebellar toxicity. To determine atrazine-exerted potential neurotoxicity, quails were treated with 50, 250 and 500 mg/kg atrazine by gavage administration for 45 days. Notably, the changes of cytochrome P450 enzyme system (CYP450s) were observed in atrazine-exposed quails. The contents of cytochrome P450 (CYP450) and Cytochrome b5 (Cyt b5) and the activities of NADPH-cytochrome c reductase (NCR), aminopyrin N-demethylase (APND) and aniline-4-hydeoxylase (AH) were increased and erythromycin N-demethylase (ERND) was decreased in quail cerebellum. Nuclear xenobiotic receptors (NXRs) and the transcriptions of NXRs-related target molecules were influenced in cerebellum. Atrazine disrupted the CYP450s balance in quail cerebellum. These results suggested that atrazine-induced cerebellar toxicity in birds was associated with activating PXR/CAR pathway responses and disrupting cytochrome P450 homeostasis. This study provided novel evidences that atrazine exposure induced cerebellar toxicity.