QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: dmd.106.013664v1 35/5/699    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lançon, A. Articles by Latruffe, N. Search for Related Content PubMed PubMed Citation Articles by Lançon, A. Articles by Latruffe, N.

SHORT COMMUNICATION

Resveratrol in Human Hepatoma HepG2 Cells: Metabolism and Inducibility of Detoxifying Enzymes

Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche 866 (Lipides, Nutrition et Cancer, équipe Biochimie Métabolique et Nutritionnelle); INSERM, Université de Bourgogne, Faculté des Sciences Gabriel, Dijon, France (A.L., B.J., D.D., G.L, N.L.); and Unité Mixte de Recherche 1234 Toxicologie Alimentaire, Institut National de la Recherche Agronomique-Université de Bourgogne, Dijon, France (N.H., J.M.H., M.C.C., Y.A.)

trans-Resveratrol is a polyphenol present in several plant species. Its chemopreventive properties against several diseases have been largely documented. To validate a model for the study of the factors influencing its biological fate at the hepatic level, the metabolism and the efflux of resveratrol were studied in the human hepatoblastoma cell line, HepG2. Comparative high-performance liquid chromatography analysis of cell culture media before and after deconjugation showed that resveratrol was rapidly conjugated; at the concentration of 10 µM, it was entirely metabolized at 8 h of incubation. Two main resveratrol metabolites, monosulfate and disulfate, were identified by atmospheric pressure chemical ionization-mass spectrometry, thanks to their quasi-molecular ion and their characteristic fragmentation. To correlate with the auto-induction of resveratrol metabolism evidenced in HepG2 cells after a pretreatment for 48 h with 10 µM resveratrol, the inducibility of phase II enzymes by resveratrol was studied by real-time quantitative reverse transcriptase-polymerase chain reaction and flow cytometry. Observed, in particular, were an increase in mRNA expression levels of three metabolizing enzymes, two isoforms of UDP-glucuronosyltransferases, UGT1A1 and UGT2B7 (5-fold increased), and a sulfotransferase, ST1E1, in cells pretreated for 24 h with 10 µM resveratrol. These results were correlated with an increase in protein expression, especially after 48 h of treatment. On the other hand, the intracellular resveratrol retention in cells treated with MK571 (3-[[3-[2-(7-chloroquinolin-2-yl)vinyl]phenyl]-(2-dimethylcarbamoylethylsulfanyl)methylsulfanyl] propionic acid), a multidrug resistance-associated protein inhibitor, strongly suggests the involvement of this ABC transporter family in the efflux of resveratrol conjugates from human liver.