Involvement of cytochrome P450 1A2 in the biotransformation of trans-resveratrol in human liver microsomes.
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Piver B, Fer M, Vitrac X, Merillon JM, Dreano Y, Berthou F, Lucas D
Involvement of cytochrome P450 1A2 in the biotransformation of trans-resveratrol in human liver microsomes.
Biochem Pharmacol. 2004 Aug 15;68(4):773-82.
- PubMed ID
- 15276085 [ View in PubMed]
- Abstract
This study was aimed at identifying the isoform(s) of human liver cytochrome P450 (CYP) involved in the hepatic biotransformation of trans-resveratrol (trans-3,5,4'-trihydroxystilbene). Trans-resveratrol metabolism was found to yield two major metabolites, piceatannol (3,5,3',4'-tetrahydroxystilbene) and another tetrahydroxystilbene named M1. Trans-resveratrol was hydroxylated to give piceatannol and M1 with apparent K(m) of 21 and 31 microM, respectively. Metabolic rates were in the range 14-101 pmol min(-1) mg(-1) protein for piceatannol and 29-161 pmol min(-1) mg(-1) protein for M1 in the 13 human liver microsomes tested. Using microsomal preparations from different human liver samples, piceatannol and M1 formation significantly correlated with ethoxy-resorufin-O-deethylation (r(2) = 0.84 and 0.88, respectively), phenacetin-O-deethylation (r(2) = 0.92 and 0.94) and immuno-quantified CYP1A2 (r(2) = 0.85 and 0.90). Formation of these metabolites was markedly inhibited by alpha-naphthoflavone and furafylline, two inhibitors of CYP1A2. Antibodies raised against CYP1A2 also inhibited the biotransformation of trans-resveratrol. In addition, the metabolism of trans-resveratrol into these two metabolites was catalyzed by recombinant human CYP1A1, CYP1A2 and CYP1B1. Our results provide evidence that in human liver, CYP1A2 plays a major role in the metabolism of trans-resveratrol into piceatannol and tetrahydroxystilbene M1.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Resveratrol Cytochrome P450 1A1 Protein Humans NoSubstrateInhibitorDetails Resveratrol Cytochrome P450 1A2 Protein Humans NoSubstrateInhibitorInducerDetails Resveratrol Cytochrome P450 1B1 Protein Humans NoSubstrateInhibitorDetails