Lycopene protects against atrazine-induced hepatotoxicity through modifications of cytochrome P450 enzyme system in microsomes

Atrazine (ATR) is primarily distributed in liver and hazardous to animal health. Cytochrome P450 enzyme system (CYP450s) is responsible for the biotransformation of toxic substances. Lycopene (LYC) prevents the herbicide-induced toxicity. However, it is unclear that LYC protects against ATR-induced hepatotoxicity via modifying CYP450s. To ascertain the chemoprevention of LYC on ATR-induced hepatotoxicity, male Kunming mice were treated with LYC (5 mg/kg) and/or ATR (50 mg/kg or 200 mg/kg) by gavage administration for 21 days. These results showed that ATR induced the increase of total CYP450 and Cytochrome b5 (Cyt b5) contents and stimulated the activities of CYP450s enzymes (erythromycin N-demethylase (ERND), aminopyrin N-demethylase (APND), aniline-4-hydeoxylase (AH) and NADPH-cytochrome c reductase (NCR)) in hepatic microsomes. The mRNA expressions of six CYP450s genes (increase: CYP1a1, CYP2a4, CYP3a57 and decrease: CYP2f2, CYP3a11, CYP4a31) were significantly influenced by ATR. LYC modulated the contents and activities of CYP450s and normalized the expressions of four CYP450s genes (CYP1b1, CYP2a4, CYP2e1, and 4A14). These findings suggested that ATR induced hepatic CYP450s disturbance and influenced the gene expression of CYP450s. Lycopene protected against hepatic CYP450s disturbance induced by ATR via modifying the hepatic CYP450s activities and transcription in mice.