Nuclear receptor AHR-mediated xenobiotic detoxification pathway involves in atrazine-induced nephrotoxicity in quail...

Atrazine (ATR), one of the most widely used pesticides in agricultural production, are gradually concerned due to potential ecosystem and health risks. Further, the induction of ATR nephrotoxicity and detoxification response is still unknown. To evaluate ATR-induced nephrotoxicity, quails were treated with 0, 50, 250 or 500 mg/kg ATR by gavage administration for 45 days. Histopathology indicated that ATR exposure caused renal tubular epithelial cell swelling and endoplasmic reticulum degeneration, suggesting that ATR exposure causes renal impairment even renal diseases. Notably, ATR interfered cytochrome P450 system (CYP450s) homeostasis by enhancing contents or activities of CYP450s (total CYP450, Cyt b5, AH, APND, NCR and ERND) and the expression of CYP450 isoforms (CYP1A, CYP1B, CYP2C and CYP3A). ATR triggered phase II detoxifying reaction, reflected by the elevated GSH level, GST activity and the up-regulation of GST isoforms (GSTa, GSTa3 and GSTt1) and GSH synthetase (GCLC). Moreover, ABC transporters were activated to expel ATR from the body by increasing expression of MRP1 and P-GP gene. Accompanying these alterations, the nuclear receptors (AHR, CAR and PXR) were activated by ATR in a dose-dependent manner. Analysis results of present study demonstrated that the induction of phase II detoxifying enzyme system and ABC transporters could be modulated by nuclear receptors response and CYP450s disturbance in low-dose ATR-treated quail. In conclusion, all data suggested that nuclear receptors AHR-mediated detoxification pathway was involved in ATR-induced nephrotoxicity. These results provided new evidence about the nephrotoxic effects of ATR on the response of biotransformation and detoxification system.