title: A comprehensive evaluation of the [2-14C](-)-epicatechin metabolome in rats.
abstract: Following ingestion of [2-14C](-)-epicatechin by rats, radioactivity in urine, feces, body fluids and tissues collected over a 72h period, was measured and14C-metabolites were analyzed by HPLC-MS2with 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 1h 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 6-12h 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.
authors: School of Medicine, Dentistry and Nursing, College of Medical, Veterinary and Life Science, University of Glasgow, Glasgow, UK.
authors: Gina
authors: G
authors: Borges
authors: School of Medicine, Dentistry and Nursing, College of Medical, Veterinary and Life Science, University of Glasgow, Glasgow, UK.
authors: Justin J J
authors: JJJ
authors: van der Hooft
authors: School of Medicine, Dentistry and Nursing, College of Medical, Veterinary and Life Science, University of Glasgow, Glasgow, UK. Electronic address: alan.crozier44@gmail.com.
authors: Alan
authors: A
authors: Crozier
mesh_terms: D000818:Animals; D001711:Biotransformation; D002250:Carbon Radioisotopes; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine*; D004386:Duodenum / Q000378:metabolism; D005243:Feces / Q000737:chemistry; D020719:Glucuronides / Q000097:blood; D006626:Hippurates / Q000097:blood; D006801:Humans; D007082:Ileum / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism; D007783:Lactones / Q000097:blood; D008297:Male; D055442:Metabolome; D008745:Methylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
chemical_list: D002250:Carbon Radioisotopes; D020719:Glucuronides; D006626:Hippurates; D007783:Lactones; C523149:epicatechin-glucuronide; D002392:Catechin; C037556:gamma-valerolactone; C030514:hippuric acid
keywords: Absorption; Acute ingestion; Disposition; Excretion; Metabolism; Rats; [2-(14)C](–)-Epicatechin