
Induction of liver cytochrome P450 1A2 expression by flutamide in rats 1
Author(s) -
WANG Haixue,
LIU Xiao,
XU Changjiang,
MA Xiaochao,
LONG Jianer,
LI Duan
Publication year - 2005
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2005.00211.x
Subject(s) - flutamide , cytochrome p450 , chemistry , medicine , pharmacology , endocrinology , biology , metabolism , androgen receptor , prostate cancer , cancer
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/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:CYP1A2 mRNAlevels after flutamide treatment at 100 mg/kgand200mg/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.