Document Detail


Hepatic metabolism of diallyl disulphide in rat and man.
MedLine Citation:
PMID:  14742141     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. The metabolism of diallyl disulphide was investigated in vitro with rat and human liver cell subfractions and ex vivo with an isolated perfused rat liver. 2. Diallyl disulphide was oxidized to diallylthiosulphinate by rat liver microsomes with an apparent K(m) = 0.86 +/- 0.1 mM and an apparent V(max) = 0.47 +/- 0.12 nmol min(-1) mg(-1) protein (mean +/- SE). Both cytochrome P450 (CYP) and flavin-containing monooxygenases were involved, with CYP2B1/2 and CYP2E1 being the most active CYP enzymes. 3. In rat and man, microsomal oxidation of allylmethyl sulphide to allylmethyl sulphoxide and allylmethyl sulphone also occurred, although at a low rate. Diallyl disulphide was also metabolized to allylglutathione sulphide and allylmercaptan. In addition, diallylthiosulphinate reacted non-enzymatically with glutathione to form allylglutathione sulphide. 4. When an isolated rat liver was perfused with diallyl disulphide, the metabolites allyl mercaptan, allylmethyl sulphide, allylmethyl sulphoxide, allylmethyl sulphone and allylglutathione sulphide were detected primarily within the liver tissue, with only small amounts of metabolites found in the bile and perfusion medium. The pharmacokinetic parameters for diallyl disulphide were t(1/2) = 6.09 min; AUC(0- infinity ) = 4.77 min mmol l(-1); clearance = 34.22 ml min(-1). 5. A scheme for the metabolism of diallyl disulphide in rat and man is proposed.
Authors:
E Germain; J Chevalier; M-H Siess; C Teyssier
Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Xenobiotica; the fate of foreign compounds in biological systems     Volume:  33     ISSN:  0049-8254     ISO Abbreviation:  Xenobiotica     Publication Date:  2003 Dec 
Date Detail:
Created Date:  2004-01-26     Completed Date:  2004-11-04     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1306665     Medline TA:  Xenobiotica     Country:  England    
Other Details:
Languages:  eng     Pagination:  1185-99     Citation Subset:  IM    
Affiliation:
Unité Mixte de Recherche de Toxicologie Alimentaire, Institut National de Recherche Agronomique--Université de Bourgogne, Dijon Cedex, France.
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MeSH Terms
Descriptor/Qualifier:
Aged
Allyl Compounds / metabolism*
Animals
Area Under Curve
Aryl Hydrocarbon Hydroxylases / metabolism
Cytochrome P-450 CYP2B1 / metabolism
Cytochrome P-450 CYP2E1 / metabolism
Disulfides / metabolism*
Enzymes / metabolism*
Female
Humans
Liver / metabolism*
Male
Microsomes, Liver / metabolism
Middle Aged
Oxidation-Reduction
Perfusion
Rats
Steroid Hydroxylases / metabolism
Sulfur Compounds / metabolism
Chemical
Reg. No./Substance:
0/Allyl Compounds; 0/Disulfides; 0/Enzymes; 0/Sulfur Compounds; 2179-57-9/diallyl disulfide; EC 1.14.-/Steroid Hydroxylases; EC 1.14.14.1/Aryl Hydrocarbon Hydroxylases; EC 1.14.14.1/Cytochrome P-450 CYP2B1; EC 1.14.14.1/Cytochrome P-450 CYP2E1; EC 1.14.14.1/steroid 16-beta-hydroxylase

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


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