Identification of novel urinary metabolites of the lipid peroxidation product 4-hydroxy-2-nonenal in rats.
Following iv administration of 4-hydroxy-2-nonenal (HNE) and [4-3H]HNE to rats, 15 polar urinary metabolites accounting for about 50% of the urinary radioactivity were separated by HPLC. Among them, eight major compounds and tritiated water were quantified. The metabolites were unequivocally characterized using GC/MS and ESI/MS/MS/MS. Most of "HNE polar metabolites" originate from omega-oxidation of 4-hydroxy-2-nonenoic acid (HNA): 9-hydroxy-HNA, its mercapturic acid conjugate, and two diastereoisomers of the corresponding lactone. The oxidation of 9-hydroxy-HNA by alcohol and aldehyde dehydrogenases leads to the excretion 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-hydroxylated, leading to 9-hydroxy-DHN which was excreted as a mercapturic acid conjugate (two diastereoisomers).
Alary
J
J
Laboratoire des Xénobiotiques, INRA, BP3, 31931 Toulouse Cedex, France.
Debrauwer
L
L
Fernandez
Y
Y
Paris
A
A
Cravedi
J P
JP
Dolo
L
L
Rao
D
D
Bories
G
G
D000447:Aldehydes / Q000378:metabolism / Q000652:urine*; D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism / Q000652:urine*; D008401:Gas Chromatography-Mass Spectrometry; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D015227:Lipid Peroxidation; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016339:Spectrometry, Mass, Fast Atom Bombardment
D000447:Aldehydes; D015853:Cysteine Proteinase Inhibitors; C027576:4-hydroxy-2-nonenal