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Induction of liver cytochrome P450 1A2 expression by flutamide in rats
Hai-xue Wang1, Xiao Liu, Chang-jiang Xu
1Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 200032, China.
Aim:
To investigate the modulation of liver cytochrome P450 1A2 (CYP1A2) expression by giving flutamide to adult rats.
Methods:
Rats were given 50, 100, and 200 mg/kg po 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:
CYP1A2 mRNA 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, CYP1A2 protein increased 1.78 and 2.89-fold and CYP1A2 activity increased approximately 1.65 and 2.83-fold, respectively, relative to controls. Flutamide treatment at 50 mg/kg had no significant effect on CYP1A2 mRNA, protein, or enzyme activity.
Conclusion:
Giving rats flutamide induced liver CYP1A2 expression in a dose-dependent manner.
