Identification of novel urinary metabolites of the lipid peroxidation product 4-hydroxy-2-nonenal in rats

被引:34
作者
Alary, J [1 ]
Debrauwer, L [1 ]
Fernandez, Y [1 ]
Paris, A [1 ]
Cravedi, JP [1 ]
Dolo, L [1 ]
Rao, D [1 ]
Bories, G [1 ]
机构
[1] INRA, Lab Xenobiot, F-31931 Toulouse, France
关键词
D O I
10.1021/tx980068g
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Following iv administration of 4-hydroxy-2-nonenal (HNE) and [4-H-3]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).
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页码:1368 / 1376
页数:9
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