Chen L, Bondoc F Y, Lee M J, Hussin A H, Thomas P E, Yang C S
Laboratory for Cancer Research, College of Pharmacy, Rutgers University, Piscataway, NJ 08855, USA.
Drug Metab Dispos. 1996 May;24(5):529-33.
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.
先前的报告表明，用绿茶或红茶提取物处理大鼠会增加CYP1A2活性，但在我们的初步研究中，脱咖啡因绿茶未观察到这种诱导作用。在此，我们报告了一项关于不同茶制剂和咖啡因作为诱导剂对CYP1A2诱导作用的比较研究。当将绿茶（2%）或红茶（2%）作为唯一饮用水源给予雄性Fischer 344大鼠21天时，观察到肝微粒体中CYP1A2依赖性O-甲氧基试卤灵脱甲基酶（MROD）活性分别诱导了2.4倍或2.7倍。用咖啡因（0.04%）处理大鼠也导致MROD活性增加了1.9倍，但脱咖啡因绿茶（0.8%）未引起这种诱导。以绿茶（2%）或咖啡因（0.055%）作为唯一饮用水源处理大鼠1、3和7天，也显示出MROD活性有相当的诱导作用（从1.7倍到2.1倍）。通过胃内给予咖啡因（100 mg/kg）也显示出诱导作用。通过免疫印迹分析确定，饮用绿茶、红茶和咖啡因引起的诱导MROD活性与肝微粒体CYP1A2蛋白的增加相对应。还测量了血浆中茶多酚和咖啡因的浓度。仅观察到MROD活性的增加与血浆咖啡因水平密切相关（r = 0.736，n = 10，p = 0.015），与茶多酚的综合水平无关（r = 0.058，n = 6，p = 0.913）。本研究确定咖啡因是CYP1A2的诱导剂，并证明咖啡因而非茶多酚是茶中负责诱导该酶的成分。
