title: The catechol-O-methyltransferase inhibitor, tolcapone, increases the bioavailability of unmethylated (-)-epigallocatechin-3-gallate in mice.
abstract: (-)-Epigallocatechin-3-gallate (EGCG), has been shown to inhibit cancerin vivo. EGCG, however, is rapidly methylated by catechol-O-methyl transferase (COMT), which reduces its cancer preventive efficacy. Tolcapone (TOL), is a clinically-used COMT inhibitor. Here, we examined the effect of TOL on the bioavailability of EGCG in male CF-1 mice. Plasma and tissue levels of EGCG and its methyl metabolites were determined following intragastric administration of EGCG (100 mg/kg), TOL (30 mg/kg), or the combination. In mice treated with EGCG, unmethylated plasma EGCG accounted for 63.4 % of the total. Co-administration of TOL increased this fraction to 87.9 %. In the urine, unmethylated EGCG accounted for 29.2 % of the total, whereas treatment with EGCG plus TOL increased this to 81.8 %. Similar effects were observed in the major organs examined. TOL effectively inhibited the methylation of EGCGin vivo. Future studies should examine the cancer preventive effects of the combination.
authors.affiliation: Department of Food Science, The Pennsylvania State University, University Park, PA, USA.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Forester
authors.affiliation: Department of Food Science, The Pennsylvania State University, University Park, PA, USA ; Center for Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, PA, USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Lambert
keywords: (−)-epigallocatechin-3-gallate; bioavailability; catechol-O-methyltransferase; green tea; tolcapone