title: Metabolism of 4-hydroxynonenal, a cytotoxic product of lipid peroxidation, in rat precision-cut liver slices.
abstract: 4-Hydroxy-2-nonenal (HNE) is a major aldehydic product of lipid peroxidation known to exert several biological and cytotoxic effects. The in vitro metabolism of [4-(3)H]-HNE by rat precision-cut liver slices was investigated. Liver slices rapidly metabolize HNE - about 85% of 0.1 microM [4-(3)H]-HNE was degraded within 5 min of incubation. The main metabolites of HNE identified were 4-hydroxynonenoic acid (HNA), glutathione-HNE-conjugate (HNE-GSH), glutathione-1,4-dihydroxynonene-conjugate (DHN-GSH) and cysteine-HNE-conjugate (HNE-CYS). Whereas glutathione conjugation demonstrated saturation kinetics (K(m)=412.2+/-152.7 microM and V(max)=12.3+/-2.5 nmol h(-1) per milligram protein), HNA formation was linear up to 500 microM HNE in liver slices. In contrast to previous reports, no trace of the corresponding alcohol of the HNE, 1,4-dihydroxynon-2-ene was detected in the present study. Furthermore, the beta-oxidation of HNA including the formation of tritiated water was demonstrated. The identification of 4-hydroxy-9-carboxy-2-nonenoic acid and 4,9-dihydroxynonanoic acid demonstrated that omega-oxidation significantly contributes to the biotransformation of HNE in liver slices.
authors.affiliation: Laboratoire des Xénobiotiques, INRA, BP.3, 31931, Toulouse, France.
authors.forename: A
authors.initials: A
authors.lastname: Laurent
authors.forename: E
authors.initials: E
authors.lastname: Perdu-Durand
authors.forename: J
authors.initials: J
authors.lastname: Alary
authors.forename: L
authors.initials: L
authors.lastname: Debrauwer
authors.forename: J P
authors.initials: JP
authors.lastname: Cravedi
mesh_terms: D000447:Aldehydes / Q000378:metabolism*; D000475:Alkenes / Q000032:analysis; D000818:Animals; D001711:Biotransformation / Q000502:physiology; D002250:Carbon Radioisotopes / Q000032:analysis; D002470:Cell Survival; D002851:Chromatography, High Pressure Liquid; D046508:Culture Techniques; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism*; D005229:Fatty Acids, Monounsaturated / Q000032:analysis / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000032:analysis / Q000138:chemical synthesis; D005978:Glutathione / Q000032:analysis / Q000378:metabolism; D006880:Hydroxy Acids / Q000032:analysis / Q000138:chemical synthesis; D007700:Kinetics; D015227:Lipid Peroxidation / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D017208:Rats, Wistar; D014316:Tritium / Q000032:analysis
chemical_list: C406868:4-hydroxy-1,9-dicarboxy-2-nonene; C406867:4-hydroxynonenoic acid; D000447:Aldehydes; D000475:Alkenes; D002250:Carbon Radioisotopes; D015853:Cysteine Proteinase Inhibitors; D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated; D006880:Hydroxy Acids; C406871:glutathione-1,4-dihydroxynonene conjugate; D014316:Tritium; C009785:4-pentenoic acid; D005978:Glutathione; C027576:4-hydroxy-2-nonenal