title: Inhibition of murine hepatic cytochrome P450 activities by natural and synthetic phenolic compounds.
abstract: 1. The effect of the phenolic compounds protocatechuic acid, chlorogenic acid, tannic acid, gallates and silybin on ethoxyresorufin O-dealkylase (CYP1A1), methoxyresorufin O-dealkylase (CYP1A2) and pentoxy-O-dealkylase (CYP2B) was examined in mouse liver microsomes from induced animals. 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 microM. Synthetic dodecyl gallate was also relatively selective toward this enzyme activity with an IC50=120 microM. 3. Protocatechuic acid, chlorogenic and silybin were more selective towards PROD and MROD activities. Their relative inhibitory potency for PROD activity was as follows: chlorogenic acid > protocatechuic acid > silybin > dodecyl gallate > propyl gallate. Protocatechuic acid was a more effective inhibitor of MROD activity than chlorogenic acid, and propyl gallate more effective than dodecyl gallate. Thus, no clear structure-activity or selectivity relationship was observed. 4. Analysis of the kinetics of inhibition revealed that the inhibition in most cases was non-competitive in nature.
authors.affiliation: K. Marcinkowski University of Medical Sciences, Department of Pharmaceutical Biochemistry, Poznan, Poland.
authors.forename: W
authors.initials: W
authors.lastname: Baer-Dubowska
authors.forename: H
authors.initials: H
authors.lastname: Szaefer
authors.forename: V
authors.initials: V
authors.lastname: Krajka-Kuzniak
mesh_terms: D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D019362:Cytochrome P-450 CYP2B1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D051379:Mice; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D010636:Phenols; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; C076307:methoxyresorufin-O-demethylase; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1