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 - Funding Information:
We would like to thank Drs. Sudathip Sae-tan, Tongtong Xu, Yeyi Gu, Ms. Amy Brownschidle, and Ms. Ling Tao for assisting in harvesting the tissue samples. We would also like to thank Dr. Ryan J. Elias for the use of his LC–MS. This work was funded in part by a grant from the National Institutes of Health ( AT004678 ) and the American Institute for Cancer Research ( 10A102 ) to JDL.
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 -
