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2 Acta Biochimica Polonica

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

100%

Mikstacka R. , Gnojkowski J. , Baer-Dubowska W.

tom 49

nr 4

917-925

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

Monoclonal antibody characterization of NADH- and NADPH-dependent hydroxylation of benzo(a)pyrene in liver microsomes from 5,6-benzoflavone-induced C57B1/6 mice

100%

Brauze D. , Mikstacka R. , Pelkonen O.

nr 2

219-225