Inhibition of murine hepatic cytochrome P450 activities by natural and synthetic phenolic compounds

Xenobiotica. 1998 Aug;28(8):735-43. doi: 10.1080/004982598239155.

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.

MeSH terms

  • Animals
  • Cytochrome P-450 CYP1A1 / antagonists & inhibitors
  • Cytochrome P-450 CYP1A1 / metabolism
  • Cytochrome P-450 CYP2B1 / antagonists & inhibitors
  • Cytochrome P-450 CYP2B1 / metabolism
  • Cytochrome P-450 Enzyme Inhibitors*
  • Cytochrome P-450 Enzyme System / metabolism
  • Enzyme Inhibitors / pharmacology*
  • Female
  • Isoenzymes / antagonists & inhibitors*
  • Isoenzymes / metabolism
  • Kinetics
  • Liver / drug effects*
  • Liver / enzymology*
  • Mice
  • Oxidoreductases / antagonists & inhibitors
  • Oxidoreductases / metabolism
  • Phenols / pharmacology*

Substances

  • Cytochrome P-450 Enzyme Inhibitors
  • Enzyme Inhibitors
  • Isoenzymes
  • Phenols
  • Cytochrome P-450 Enzyme System
  • Oxidoreductases
  • methoxyresorufin-O-demethylase
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 CYP2B1