INHIBITION OF MURINE HEPATIC CYTOCHROME-P450 ACTIVITIES BY NATURAL AND SYNTHETIC PHENOLIC-COMPOUNDS

1. The effect of the phenolic compounds protocatechuic acid, chlorogen ic acid, tannic acid, gallates and silybin on ethoxyresorufin O-dealky lase (CYP1A1), methoxyresorufin O-dealkylase (CYP1A2) and pentoxy-O-de alkylase (CYP2B) was examined in mouse liver microsomes from induced a nimals. 2. All compounds tested could inhibit cytochrome P450-mediated enzyme activities, but to different extents. Tannic acid was the most potent inhibitor, especially toward EROD activity with an IC50 = 2.6 mu M. Synthetic dodecyl gallate was also relatively selective toward t his enzyme activity with an IC50 = 120 mu M. 3. Protocatechuic acid, c hlorogenic and silybin were more selective towards PROD and MROD activ ities. Their relative inhibitory potency for PROD activity was as foll ows: chlorogenic acid > protocatechuic acid > silybin > dodecyl gallat e > propyl gallate. Protocatechuic acid was a more effective inhibitor of MROD activity than chlorogenic acid, and propyl gallate more effec tive than dodecyl gallate. Thus, no clear structure-activity or select ivity relationship was observed. 4. Analysis of the kinetics of inhibi tion revealed that the inhibition in most cases was non-competitive in nature.