Effect of natural phenols on the catalytic activity of cytochrome P450 2E1.
The effect of protocatechuic acid, tannic acid and trans-resveratrol on the activity of p-nitrophenol hydroxylase (PNPH), an enzymatic marker of CYP2E1, was examined in liver microsomes from acetone induced mice. trans-Resveratrol was found to be the most potent inhibitor (IC(50) = 18.5 +/- 0.4 microM) of PNPH, while protocatechuic acid had no effect on the enzyme activity. Tannic acid with IC(50) = 29.6 +/- 3.3 microM showed mixed- and trans-resveratrol competitive inhibition kinetics (K(i) = 1 microM and 2.1 microM, respectively). Moreover, trans-resveratrol produced a NADPH-dependent loss of PNPH activity, suggesting mechanism-based CYP2E1 inactivation. These results indicate that trans-resveratrol and tannic acid may modulate cytochrome P450 2E1 and influence the metabolic activation of xenobiotics mediated by this P450 isoform.
Mikstacka
Renata
R
Department of Pharmaceutical Biochemistry, University of Medical Sciences, Grunwaldzka 6, 60-780 Poznań, Poland. rmikstac@mail.am.poznan.pl
Gnojkowski
Jerzy
J
Baer-Dubowska
Wanda
W
D000818:Animals; D001667:Binding, Competitive; D002384:Catalysis / Q000187:drug effects; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism*; D065691:Cytochrome P-450 CYP2E1 Inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D047348:Hydrolyzable Tannins / Q000494:pharmacology; D006900:Hydroxylation / Q000187:drug effects; D020128:Inhibitory Concentration 50; D007700:Kinetics; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D015394:Molecular Structure; D010636:Phenols / Q000494:pharmacology*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology; D013379:Substrate Specificity
D065691:Cytochrome P-450 CYP2E1 Inhibitors; D004791:Enzyme Inhibitors; D047348:Hydrolyzable Tannins; D010636:Phenols; D013267:Stilbenes; D019392:Cytochrome P-450 CYP2E1; D000077185:Resveratrol