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Accumulation of (-)-Epicatechin Metabolites in Rat Plasma after Oral Administration and Distribution of Conjugation Enzymes in Rat Tissues

Manuscript received 1 October 1997. Initial reviews completed 7 November 1997. Revision accepted 23 February 1998.

Mariusz K. Piskula and Junji Terao*,

Institute of Animal Reproduction and Food Research, 10-718 Olsztyn, Poland and * Department of Nutrition, School of Medicine, The University of Tokushima, Tokushima 770, Japan

Absorption of orally administered (-)-epicatechin (EC) in rats was studied to obtain plasma pharmacokinetic profiles of EC metabolites. Rats were administered 172 µmol/kg body weight of EC, and blood was collected from the tail for 8 h after administration. Seven groups of compounds possessing the basic structure of EC were identified by using a combination of enzymatic hydrolysis, HPLC and electron impact mass spectrometry. Metabolites were quantified with a new, simple and sensitive method using HPLC with electrochemical detection. Ingested EC was absorbed from the alimentary tract and was present in the rat common blood circulation in the form of glucuronide and/or sulfate conjugates. The activity of conjugative enzymes in rat tissues was studied. The highest activity of glucuronosyltransferase was found in the intestinal mucosa of both of the small and large intestine; the highest activity of phenolsulfotransferase occurred in the liver, and that of catechol-O-methyl transferase was found in the liver and kidney. It has been proposed that the first detoxification step of dietary EC, namely, glucuronidation, occurs at the level of the intestinal mucosa in rats, and EC enters the common blood circulation exclusively in the glucuronized form. The compound is then sulfated in the liver and methylated in the liver and kidney. Because ingested EC undergoes extensive conjugation, its biological activities previously demonstrated in vitro may not be occurring in in vivo systems.

Key words: rats, (-)-epicatechin, absorption, conjugate, blood.

The Journal of Nutrition Vol. 128 No. 7 July 1998, pp. 1172-1178
Copyright ©1998 by the American Society for Nutritional Sciences




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Copyright © 1998 by American Society for Nutrition