Resveratrol Modulates Drug and Carcinogen Metabolizing Enzymes in a Healthy Volunteer Study
| Autor: | David S. Alberts, Chiu Hsieh Hsu, Jessica A. Miller, Marjorie Perloff, Donna R. Vining, James A. Crowell, Linda L. Garland, Wade M. Chew, H-H. Sherry Chow |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Adult
Male Cancer Research CYP2D6 Resveratrol Pharmacology Article chemistry.chemical_compound Enzyme activator Young Adult Cytochrome P-450 Enzyme System Stilbenes Medicine Humans CYP2C9 Chromatography High Pressure Liquid CYP3A4 biology business.industry organic chemicals CYP1A2 Cytochrome P450 Middle Aged Antineoplastic Agents Phytogenic Healthy Volunteers Enzyme Activation Oncology chemistry Pharmaceutical Preparations Health Phase II Detoxification Inactivation Metabolic biology.protein Carcinogens Female business |
| Popis: | 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-π 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-π 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. Cancer Prev Res; 3(9); 1168–75. ©2010 AACR. |
| Databáze: | OpenAIRE |
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