Document Detail


Comparison of genistein metabolism in rats and humans using liver microsomes and hepatocytes.
MedLine Citation:
PMID:  18063284     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Species differences and metabolism are the most crucial factors in considering the effects of genistein. The aim of this study was to have a better knowledge of the metabolic fate of genistein in humans as compared with rats. For this purpose, radiolabeled genistein was incubated with human and rat liver microsomes and with cryopreserved hepatocytes from both species. Incubations were performed using a wide range of genistein concentrations to analyze the kinetics of formation of the metabolites. Metabolite profiling was obtained using an HPLC system connected to a radioactivity detector. Identification of the metabolites was based on their retention times as compared with those of authentic standards and on LC-MS (ESI-MS/MS) or NMR analyses. In both species, liver microsomes produced the same three hydroxylated metabolites (8-OH, 6-OH and 3'-OH-genistein) whereas cryopreserved hepatocytes produced the same glucurono- and sulfo-conjugates (genistein 4'-O-sulfate 7-O-glucuronide, genistein 7-O-glucuronide, genistein 4'-O-glucuronide, genistein 7-O-sulfate and genistein 4'-O-sulfate). The rate of metabolism varied with species. 3'-Hydroxygenistein was the predominant metabolite produced by rat liver microsomes, whereas in humans 3'-hydroxy and 8-hydroxygenistein were produced in the same range. In both human and rat hepatocyte incubations, genistein 7-O-glucuronide represented more than 50% of the incubated dose. Our results on hepatocytes confirmed the predominance of conjugation reaction compared to oxidative reaction observed in vivo.
Authors:
Julian Bursztyka; Elisabeth Perdu; Jacques Tulliez; Laurent Debrauwer; Georges Delous; Cécile Canlet; Georges De Sousa; Roger Rahmani; Emilio Benfenati; Jean-Pierre Cravedi
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-10-30
Journal Detail:
Title:  Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association     Volume:  46     ISSN:  0278-6915     ISO Abbreviation:  Food Chem. Toxicol.     Publication Date:  2008 Mar 
Date Detail:
Created Date:  2008-02-04     Completed Date:  2008-06-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8207483     Medline TA:  Food Chem Toxicol     Country:  England    
Other Details:
Languages:  eng     Pagination:  939-48     Citation Subset:  IM    
Affiliation:
UMR 1089 Xénobiotiques, INRA, Toulouse Cedex 9, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Chromatography, Liquid
Female
Genistein / pharmacokinetics*
Hepatocytes / metabolism*
Humans
Magnetic Resonance Spectroscopy
Male
Microsomes, Liver / metabolism*
Rats
Rats, Sprague-Dawley
Spectrometry, Mass, Electrospray Ionization
Tandem Mass Spectrometry
Chemical
Reg. No./Substance:
446-72-0/Genistein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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