Acta Pharmacologica Sinica 2005 November; 26 (11): 1382-1386; doi: 10.1111/j.1745-7254.2005.00211.x

Acta Pharmacologica Sinica 2005 November; 26 (11): 1382-1386; doi: 10.1111/j.1745-7254.2005.00211.x

Original Article

Induction of liver cytochrome P450 1A2 expression by flutamide in rats¹

Hai-xue WANG, Xiao LIU, Chang-jiang XU, Xiao-chao MA³, Jian-er LONG⁴, Duan LI^4,5

²Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 200032, China; ³State Key Laboratory of Drug Research, Shanghai Institute of Biological Sciences, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200031, China; ⁴Institute of Molecular Virus, School of Basic Medical Science, Fudan University, Shanghai 200031, 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.

Keywords: flutamide; cytochrome P450 1A2; induction

¹Project supported by Fudan University Innovation Foundation (No CQF303801).
⁵Correspondence to Prof Duan LI.
Phn 86-21-5423-7465.
E-mail dli@shmu.edu.cn
Received 2005-06-24 Accepted 2005-08-15

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