Alary J, Debrauwer L, Fernandez Y, Paris A, Cravedi J P, Dolo L, Rao D, Bories G
Laboratoire des Xénobiotiques, INRA, BP3, 31931 Toulouse Cedex, France.
Chem Res Toxicol. 1998 Nov;11(11):1368-76. doi: 10.1021/tx980068g.
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).
给大鼠静脉注射4-羟基-2-壬烯醛（HNE）和[4-³H]HNE后，通过高效液相色谱法分离出15种极性尿代谢物，它们约占尿放射性的50%。其中，对8种主要化合物和氚化水进行了定量。使用气相色谱/质谱联用仪（GC/MS）和电喷雾串联质谱仪（ESI/MS/MS/MS）明确鉴定了这些代谢物。大多数“HNE极性代谢物”源自4-羟基-2-壬烯酸（HNA）的ω-氧化：9-羟基-HNA、其硫醚氨酸共轭物以及相应内酯的两种非对映异构体。9-羟基-HNA经醇脱氢酶和醛脱氢酶氧化后，会排出9-羧基-HNA和相应的内酯硫醚氨酸共轭物。由醇脱氢酶将HNE还原产生的1,4-二羟基-2-壬烯（DHN），在较小程度上会发生ω-羟基化，生成9-羟基-DHN，并以硫醚氨酸共轭物（两种非对映异构体）的形式排出。
