Effect of natural phenols on the catalytic activity of cytochrome P450 2E1

Abstract

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 (IC50 = 18.5 ± 0.4 μM) of PNPH, while protocatechuic acid had no effect on the enzyme activity. Tannic acid with IC50 = 29.6 ± 3.3 μM showed mixed- and trans-resveratrol competitive inhibition kinetics (K1 = 1 μM and 2.1 μM, 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.