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Drug Metabolism and Disposition Fast Forward
First published on April 15, 2005; DOI: 10.1124/dmd.104.002691


0090-9556/05/3307-1036-1043$20.00
DMD 33:1036-1043, 2005

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DISPOSITION AND METABOLISM OF [2-14C]QUERCETIN-4'-GLUCOSIDE IN RATS

Brigitte A. Graf, William Mullen, Stuart T. Caldwell, Richard C. Hartley, Garry G. Duthie, Michael E. J. Lean, Alan Crozier, and Christine A. Edwards

Plant Products and Human Nutrition Group, Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, United Kingdom (B.A.G., W.M., A.C.); Department of Chemistry, University of Glasgow, Glasgow, United Kingdom (S.T.C., R.C.H.); Rowett Research Institute, Aberdeen, United Kingdom (G.G.D.); University of Glasgow Human Nutrition Section, Division of Developmental Medicine, Royal Infirmary, Glasgow, United Kingdom (M.E.J.L.); and University of Glasgow Human Nutrition Section, Division of Developmental Medicine, Yorkhill Hospitals, Glasgow, United Kingdom (C.A.E.)

Quercetin-4'-glucoside is a major flavonol in onions, and this study investigated the absorption and fate of radiolabeled quercetin-4'-glucoside in rats. Rats ingested [2-14C]quercetin-4'-glucoside and the distribution of radioactivity throughout the body was determined after 0.5, 1, 2, and 5 h. The gastrointestinal tract, liver, kidney, and plasma were extracted, and radiolabeled components were identified and quantified using high-performance liquid chromatography with on-line radioactivity detection and tandem mass spectrometry. Two hours after dosing, all the [2-14C]quercetin-4'-glucoside had been metabolized. More than 85% of the ingested radioactivity was present in the gastrointestinal tract at all time points with ~6% being absorbed and present in blood and internal organs, primarily the liver and kidneys. More than 95% of the absorbed radioactivity was in the form of >20 different methylated glucuronated and/or sulfated quercetin conjugates. Five hours after ingestion, the main radiolabeled metabolites were quercetin diglucuronides in the gut, liver, and kidneys and glucuronyl sulfates of methylated quercetin in plasma. The main site of quercetin metabolism seemed to be the gastrointestinal tract. Quercetin metabolites may have a major influence on the gut mucosal epithelium and on colonic disease.


Address correspondence to: Dr. C. A. Edwards, Human Nutrition Section, University of Glasgow Division of Developmental Medicine, Yorkhill Hospitals, Glasgow G3 8SJ, UK. E-mail: cae1n{at}clinmed.gla.ac.uk




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