TY - JOUR
T1 - The catechol-O-methyltransferase inhibitor, tolcapone, increases the bioavailability of unmethylated (-)-epigallocatechin-3-gallate in mice
AU - Forester, Sarah C.
AU - Lambert, Joshua D.
N1 - Publisher Copyright:
© 2015 Elsevier Ltd.
PY - 2015/8/1
Y1 - 2015/8/1
N2 - (-)-Epigallocatechin-3-gallate (EGCG), has been shown to inhibit cancer in 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 EGCG in vivo. Future studies should examine the cancer preventive effects of the combination.
AB - (-)-Epigallocatechin-3-gallate (EGCG), has been shown to inhibit cancer in 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 EGCG in vivo. Future studies should examine the cancer preventive effects of the combination.
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U2 - 10.1016/j.jff.2015.05.012
DO - 10.1016/j.jff.2015.05.012
M3 - Article
C2 - 26213577
AN - SCOPUS:84938828545
SN - 1756-4646
VL - 17
SP - 183
EP - 188
JO - Journal of Functional Foods
JF - Journal of Functional Foods
ER -