Add time:08/25/2019         Source:sciencedirect.com

Following ingestion of [2-14C](–)-epicatechin by rats, radioactivity in urine, feces, body fluids and tissues collected over a 72 h period, was measured and 14C-metabolites were analyzed by HPLC-MS2 with a radioactivity monitor. In total 78% of the ingested radioactivity was absorbed from the gastrointestinal tract (GIT), and then rapidly eliminated from the circulatory system via renal excretion. A peak plasma concentration occurred 1 h after intake corresponding to ~0.7% of intake. Low amounts of radioactivity, <2% of intake, appeared transiently in body tissues. Glucuronidation and methylation of (–)-epicatechin began in the duodenum but occurred more extensively in the jejunum/ileum. Radioactivity reaching the cecum after 6–12 h was predominantly in the form of the ring fission metabolites 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone and 5-(3′,4′-dihydroxyphenyl)-γ-hydroxyvaleric acid along with smaller amounts of their phase II metabolites. Low levels of metabolites were detected in the colon. Of the ingested radioactivity, 19% was voided in feces principally as ring-fission metabolites. The main components in plasma were (–)-epicatechin-5-O-glucuronide and 3′-O-methyl-(–)-epicatechin-5-O-glucuronide with small amounts of (–)-epicatechin, 3′-O-methyl-(–)-epicatechin, 5-(3′-hydroxyphenyl)-γ-hydroxyvaleric acid-4′-glucuronide and hippuric acid also being detected. No oxidized products of (–)-epicatechin were detected. No compelling evidence was obtained for biliary recycling of metabolites. The findings demonstrate substantial differences in the metabolism of (–)-epicatechin by rats and humans. Caution should, therefore, be exercised when using animal models to draw conclusions about effects induced by (–)-epicatechin intake in humans.

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