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First published on April 15, 2005; DOI: 10.1124/dmd.104.002691

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Received for publication November 2, 2004.
Revised April 11, 2005.
Accepted for publication April 12, 2005.

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

Brigitte A Graf 1, William Mullen 1, Caldwell T Stewart 2, Richard C Hartley 1, Gary G Duthie 3, Michael EJ Lean 1, Alan Crozier 1, Christine Ann Edwards 1*

1 Glasgow University 2 University of Glasgow 3 Rowett Research Institute

* Address correspondence to: E-mail: cae1n{at}clinmed.gla.ac.uk

Abstract

Quercetin-4'-glucoside is a major flavonol in onions and this study investigated the absorption and fate of radiolabelled 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 radiolabelled components 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 metabolised. Over 85% of the ingested radioactivity was present in the gastrointestinal-tract at all time points with ca. 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 sulphated quercetin conjugates. Five hours after ingestion, the main radiolabelled metabolites were quercetin di-glucuronides in the gut, liver, kidney, and glucuronyl sulphates of methylated quercetin in plasma. The main site of quercetin metabolism appeared to be the gastrointestinal tract. Quercetin metabolites may have a major influence on the gut mucosal epithelium and on colonic disease.


Key words: absorption, antioxidants, intestinal bioavailability, physiologically-based modeling


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