Metabolites and tissue distribution of resveratrol in the pig

Scope: trans-Resveratrol (RES) and/(or) its metabolites exert many effects in vivo. Our aim was to study the metabolism and tissue distribution of RES using the pig, a mammal physiologically close to humans. Methods and results: Forty-seven tissues, organs and fluids were analyzed 6h after intragastric RES administration (5.9mg/kg body weight) using HPLC-MS/MS. Twelve RES and seven dihydroresveratrol (DH-RES) metabolites were detected. DH-RES was the main metabolite in cecum, colon and rectum, whereas RES-3-O-glucuronide was the most abundant one in fluids and organs. Approximately 74.5% of the total RES administered was recovered in the form of RES, DH-RES and derived metabolites (65.1% along the gastrointestinal tract, 7.7% in urine, 1.2% in bile and 0.5% in organs). We report here, for the first time, the occurrence of RES ribosyl-sulfate derivative, DH-RES diglucuronide, DH-RES sulfoglucuronide and DH-RES disulfate as well as the metabolic profile of RES and DH-RES in the aorta, lymph, lymph node, ovaries, uterus, cerebellum, pancreas, urinary bladder tissue, fat and muscle. Conclusion: This study contributes to the clarification of the metabolism and tissue distribution of RES and could help to further understand the mechanisms underlying its effects. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.This work has been supported by the Projects CICYTBFU2007- 60576, Fundacio´n Seneca de la Region de Murcia (grupo de excelencia GERM 06, 04486) and Consolider Ingenio 2010, CSD2007-00063 (Fun-C-Food). The authors are grateful to Dr. Alberto Quiles and Dr. Ca´ndido Gutie´rrez from the Veterinary School (Univ. Murcia, Spain) and Jose´ Luis Pineda from Proquimur S. L. (Murcia, Spain) for their assistance in some parts of the study. M. A. O. is a holder of a predoctoral JAE grant from CSIC and M. L. and R. L. of a JAE-DOC contract from CSIC (Spain).Peer Reviewe