Effect of paraquat on CYP450 isoforms activity of rats after intraperitoneal administration

Paraquat is an organic heterocyclic herbicide and defoliant agent used worldwide. However, paraquat is highly toxic to humans and animals and no effective antidote is available, which causes a high mortality rate. In order to investigate the effects of paraquat on the metabolic capacity of cytochrome P450 (CYP) enzymes, a cocktail method was employed to evaluate the activities of CYP2B1, CYP2D1, CYP1A2, CYP3A2, CYP2C11. The rats were randomly divided into paraquat group (Low, High) and control group. The paraquat group rats were given 9, 18 mg/kg (Low, High) paraquat by intraperitoneal administration. Five probe drugs (bupropion, metroprolol, phenacetin, testosterone and tolbutamide) were given to rats through intragastric administration, and the plasma concentrations were determined by UPLC-MS/MS. Statistical pharmacokinetics difference for metroprolol, testosterone and tolbutamide in rats were observed by comparing paraquat group with control group. Combined with PCR results, intraperitoneal administration of paraquat induces the activities of CYP2C11 of rats.