Due to the cytotoxicity of 4-hydroxynonenal (HNE), and to the fact that this major product of lipid peroxidation is a rather long-living compound compared with reactive oxygen species, the capability of organisms to inactivate and eliminate HNE has received increasing attention during the last decade. Several recent in vivo studies have addressed the issue of the diffusion, kinetics, biotransformation and excretion of HNE. Part of these studies are primarily concerned with the toxicological significance of HNE biotransformation and more precisely with the metabolic pathways by which HNE is inactivated and eliminated. The other aim of in vivo metabolic study is the characterisation of end-metabolites, especially in urine, in order to develop specific and non-invasive biomarkers of lipid peroxidation. When HNE is administered intravenously or intraperitoneally, it is mainly excreted into urine and bile as conjugated metabolites, in a proportion that is dependent on the administration route. However, biliary metabolites undergo an enterohepatic cycle that limits the final excretion of faecal metabolites. Only a very low amount of metabolites is found to be bound to macromolecules. The main urinary metabolites are represented by two groups of compounds. One comes from the mercapturic acid formation from (i) 1,4 dihydroxynonene-glutathione (DHN-GSH) which originates from the conjugation of HNE with GSH by glutathione-S-transferases and the subsequent reduction of the aldehyde by a member of aldo-keto reductase superfamily; (ii) the lactone of 4-hydroxynonanoic-GSH (HNA-lactone-GSH) which originates from the conjugation of HNE followed by the oxidation of the aldehyde by aldehyde dehydrogenase; (iii) HNA-GSH which originates from the hydrolysis of the corresponding lactone. The other one is a group of metabolites issuing from the omega-hydroxylation of HNA or HNA-lactone by cytochromes P450 4A, followed eventually, in the case of omega-oxidized-HNA-lactone, by conjugation with GSH and subsequent mercapturic acid formation. Biliary metabolites are GSH or mercapturic acid conjugates of DHN, HNE and HNA. Stereochemical aspects of HNE metabolism are also discussed.

中文翻译：

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体内4-羟基壬烯的命运：处置和代谢途径。

由于4-羟基壬烯醛（HNE）的细胞毒性，并且与活性氧相比，脂质过氧化的主要产物是一种寿命较长的化合物，在此期间，生物灭活和消除HNE的能力越来越受到关注。最近十年。最近的一些体内研究已经解决了HNE的扩散，动力学，生物转化和排泄的问题。这些研究的一部分主要与HNE生物转化的毒理学意义有关，更确切地说，与HNE失活和消除的代谢途径有关。体内代谢研究的另一个目的是表征最终代谢物，尤其是尿液中的代谢物，以开发脂质过氧化作用的特异性和非侵入性生物标志物。当静脉内或腹膜内施用HNE时，其主要作为结合的代谢物排泄到尿液和胆汁中，其比例取决于施用途径。但是，胆汁代谢物经历了肠肝循环，限制了粪便代谢物的最终排泄。发现只有极少量的代谢物与大分子结合。主要的尿代谢产物由两组化合物代表。一种来自（i）1,4二羟基壬烯-谷胱甘肽（DHN-GSH）的巯基酸形成，其源自谷胱甘肽S-转移酶将HNE与GSH结合，随后醛基被醛基-S-转移酶还原酮还原酶超家族 （ii）4-羟基壬酸-GSH（HNA-内酯-GSH）的内酯，其源于HNE的缀合，然后通过醛脱氢酶将醛氧化；（iii）HNA-GSH，其源于相应内酯的水解。另一类是通过细胞色素P450 4A由HNA或HNA-内酯的ω-羟基化而产生的一组代谢物，在ω-氧化的HNA-内酯的情况下，最终是与GSH结合并随后形成巯基酸。胆汁代谢产物是DHN，HNE和HNA的GSH或巯基酸结合物。还讨论了HNE代谢的立体化学方面。另一类是通过细胞色素P450 4A由HNA或HNA-内酯的ω-羟基化而产生的一组代谢物，在ω-氧化的HNA-内酯的情况下，最终是与GSH结合并随后形成巯基酸。胆汁代谢产物是DHN，HNE和HNA的GSH或巯基酸结合物。还讨论了HNE代谢的立体化学方面。另一类是通过细胞色素P450 4A由HNA或HNA-内酯的ω-羟基化而产生的一组代谢物，如果是ω-氧化的HNA-内酯，则最终与GSH结合并随后形成巯基酸。胆汁代谢产物是DHN，HNE和HNA的GSH或巯基酸结合物。还讨论了HNE代谢的立体化学方面。