Caffeine induces cytochrome P4501A2: induction of CYP1A2 by tea in rats.

Previous reports indicated that treatment of rats with green tea or black tea extracts increased CYP1A2 activity, but such an induction was not observed with decaffeinated green tea in our preliminary study. Herein we report a comparative study on the induction of CYP1A2 with different tea preparations and caffeine as an inducer. When green tea (2%) or black tea (2%) was given to male Fischer 344 rats as the sole source of drinking fluid for 21 days, a 2.4- or 2.7-fold induction, respectively, of CYP1A2-dependent O-methoxyresorufin demethylase (MROD) activity in liver microsomes was observed. Treating rats with caffeine (0.04%) also resulted in an 1.9-fold increase in the MROD activity, but decaffeinated green tea (0.8%) did not cause such an induction. Rats treated with green tea (2%) or caffeine (0.055%) as the sole source of drinking fluid for 1, 3, and 7 days also showed comparable induction (from 1.7- to 2.1-fold) of the MROD activity. The induction was also shown by intragastric administration of caffeine (100 mg/kg). The induced MROD activity caused by consumption of green tea, black tea, and caffeine corresponded to the increase in liver microsomal CYP1A2 protein, as determined by immunoblot analysis. The concentrations of tea polyphenols and caffeine in plasma were also measured. Close correlation of the increase in the MROD activity was observed only with the plasma caffeine level (r = 0.736, n = 10, p = 0.015), not with the combined tea polyphenol level (r = 0.058, n = 6, p = 0.913). The present study establishes caffeine as an inducer of CYP1A2 and demonstrates that caffeine, not tea polyphenols, is the component in tea responsible for the induction of this enzyme.