IDENTIFICATION OF NOVEL URINARY METABOLITES OF THE LIPID-PEROXIDATIONPRODUCT 4-HYDROXY-2-NONENAL IN RATS

Citation
J. Alary et al., IDENTIFICATION OF NOVEL URINARY METABOLITES OF THE LIPID-PEROXIDATIONPRODUCT 4-HYDROXY-2-NONENAL IN RATS, Chemical research in toxicology, 11(11), 1998, pp. 1368-1376
Citations number
17
Categorie Soggetti
Toxicology,"Chemistry Medicinal",Chemistry
ISSN journal
0893228X
Volume
11
Issue
11
Year of publication
1998
Pages
1368 - 1376
Database
ISI
SICI code
0893-228X(1998)11:11<1368:IONUMO>2.0.ZU;2-2
Abstract
Following iv administration of 4-hydroxy-2-nonenal (HNE) and [4-H-3]HN E to rats, 15 polar urinary metabolites accounting for about 50% of th e urinary radioactivity were separated by HPLC, Among them, eight majo r compounds and tritiated water were quantified. The metabolites were unequivocally characterized using GC/MS and ESI/MS/MS/MS. Most of ''HN E polar metabolites'' originate from omega-oxidation of 4-hydroxy-2-no nenoic acid(HNA): 9-hydroxy-HNA, its mercapturic acid conjugate, and t wo diastereoisomers of the corresponding lactone. The oxidation of 9-h ydroxy-HNA by alcohol and aldehyde dehydrogenases leads to the excreti on of 9-carboxy-HNA and of the corresponding lactone mercapturic acid conjugate. 1,4-Dihydroxy-2-nonene (DHN) originating from the reduction of HNE by alcohol dehydrogenase was to a lesser extent omega-hydroxyl ated, leading to 9-hydroxy-DHN which was excreted as a mercapturic aci d conjugate (two diastereoisomers).