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
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).