title: Resveratrol modulates drug- and carcinogen-metabolizing enzymes in a healthy volunteer study.
abstract: Resveratrol has been shown to exhibit cancer-preventive activities in preclinical studies. We conducted a clinical study to determine the effect of pharmacologic doses of resveratrol on drug- and carcinogen-metabolizing enzymes. Forty-two healthy volunteers underwent baseline assessment of cytochrome P450 (CYP) and phase II detoxification enzymes. CYP1A2, CYP2D6, CYP2C9, and CYP3A4 enzyme activities were measured by the metabolism of caffeine, dextromethorphan, losartan, and buspirone, respectively. Blood lymphocyte glutathione S-transferase (GST) activity and GST-pi level and serum total and direct bilirubin, a surrogate for UDP-glucuronosyl transferase (UGT) 1A1 activity, were measured to assess phase II enzymes. After the baseline evaluation, study participants took 1 g of resveratrol once daily for 4 weeks. Enzyme assessment was repeated upon intervention completion. Resveratrol intervention was found to inhibit the phenotypic indices of CYP3A4, CYP2D6, and CYP2C9 and to induce the phenotypic index of 1A2. Overall, GST and UGT1A1 activities were minimally affected by the intervention, although an induction of GST-pi level and UGT1A1 activity was observed in individuals with low baseline enzyme level/activity. We conclude that resveratrol can modulate enzyme systems involved in carcinogen activation and detoxification, which may be one mechanism by which resveratrol inhibits carcinogenesis. However, pharmacologic doses of resveratrol could potentially lead to increased adverse drug reactions or altered drug efficacy due to inhibition or induction of certain CYPs. Further clinical development of resveratrol for cancer prevention should consider evaluation of lower doses of resveratrol to minimize adverse metabolic drug interactions.
authors: Arizona Cancer Center, The University of Arizona, Tucson, AZ 85724, USA. schow@azcc.arizona.edu
authors: H-H Sherry
authors: HH
authors: Chow
authors: Linda L
authors: LL
authors: Garland
authors: Chiu-Hsieh
authors: CH
authors: Hsu
authors: Donna R
authors: DR
authors: Vining
authors: Wade M
authors: WM
authors: Chew
authors: Jessica A
authors: JA
authors: Miller
authors: Marjorie
authors: M
authors: Perloff
authors: James A
authors: JA
authors: Crowell
authors: David S
authors: DS
authors: Alberts
mesh_terms: D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000032:analysis / Q000097:blood / Q000494:pharmacology; D002273:Carcinogens / Q000032:analysis / Q000378:metabolism / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006262:Health; D064368:Healthy Volunteers; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics; D008297:Male; D008875:Middle Aged; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000032:analysis / Q000097:blood / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002273:Carcinogens; D004364:Pharmaceutical Preparations; D013267:Stilbenes; D003577:Cytochrome P-450 Enzyme System; D000077185:Resveratrol