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

• Published in: Xenobiotica 1998, Vol.28 (8), p.735-743
• Main Authors: BAER-DUBOWSKA, W., SZAEFER, H., KRAJKA-KUZNIAK, V.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; chlorogenic acid; cytochrome P-450; 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; dodecyl gallate; enzyme activity; Enzyme Inhibitors - pharmacology; Female; gallic acid; inhibition; Isoenzymes - antagonists & inhibitors; Isoenzymes - metabolism; Kinetics; Liver - drug effects; Liver - enzymology; Medical sciences; Mice; Oxidoreductases - antagonists & inhibitors; Oxidoreductases - metabolism; phenolic compounds; Phenols - pharmacology; Plant poisons toxicology; propyl gallate; protocatechuic acid; silybin; tannins; Toxicology
• ISSN: 0049-8254; 1366-5928
• DOI: 10.1080/004982598239155

1. The effect of the phenolic compounds protocatechuic acid, chlorogenic acid, tannic acid,gallates and silybinon 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 μM. Synthetic dodecyl gallate was also relatively selective toward this enzyme activity with an IC50 = 120 μM. 3. Protocatechuic acid,chlorogenicandsilybin were moreselectivetowards PRODand 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.