Induction of liver cytochrome P450 1A2 expression by flutamide in rats

摘要

Aim: To investigate the modulation of liver cytochrome P4501A2 (CYP1A2) expression by giving flutamide to adult rats. Methods: Rats were given 50, 100, and200 mg/kgpo of flutamide for 2 weeks. Liver CYP1A2 mRNA was measured using reverse transcription-polymerase chain reaction. CYP1A2 protein was detected using immunoblotting. CYP1A2 activity was assayed using high performance liquid chromatography, with caffeine as the CYP1A2 substrate. Results: CYP1A2mRNA levels after flutamide treatment at 100 mg/kg and 200 mg/kg were, respectively,1.86 and 3.11-fold higher than those of the control. Correspondingly, CYP1A2protein increased 1.78 and 2.89-fold and CYP1A2 activity increased approximately1.65 and 2.83-fold, respectively, relative to controls. Flutamide treatment at 50mg/kg had no significant effect on CYP1A2 mRNA, protein, or enzyme activity.Conclusion: Giving rats flutamide induced liver CYP1A2 expression in a dosedependent manner.