title: Mercapturic acid conjugates of 4-hydroxy-2-nonenal and 4-oxo-2-nonenal metabolites are in vivo markers of oxidative stress.
abstract: Oxidative stress-induced lipid peroxidation leads to the formation of cytotoxic and genotoxic 2-alkenals, such as 4-hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE). Lipid-derived reactive aldehydes are subject to phase-2 metabolism and are predominantly found as mercapturic acid (MA) conjugates in urine. This study shows evidence for the in vivo formation of ONE and its phase-1 metabolites, 4-oxo-2-nonen-1-ol (ONO) and 4-oxo-2-nonenoic acid (ONA). We have detected the MA conjugates of HNE, 1,4-dihydroxy-2-nonene (DHN), 4-hydroxy-2-nonenoic acid (HNA), the lactone of HNA, ONE, ONO, and ONA in rat urine by liquid chromatography-tandem mass spectrometry comparison with synthetic standards prepared in our laboratory. CCl(4) treatment of rats, a widely accepted animal model of acute oxidative stress, resulted in a significant increase in the urinary levels of DHN-MA, HNA-MA lactone, ONE-MA, and ONA-MA. Our data suggest that conjugates of HNE and ONE metabolites have value as markers of in vivo oxidative stress and lipid peroxidation.
authors.affiliation: Department of Pharmaceutical Sciences and the Linus Pauling Institute, Oregon State University, Corvallis Oregon 97331, USA.
authors.forename: Heather C
authors.initials: HC
authors.lastname: Kuiper
authors.forename: Cristobal L
authors.initials: CL
authors.lastname: Miranda
authors.forename: John D
authors.initials: JD
authors.lastname: Sowell
authors.forename: Jan F
authors.initials: JF
authors.lastname: Stevens
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000447:Aldehydes / Q000737:chemistry*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D002251:Carbon Tetrachloride / Q000494:pharmacology; D002853:Chromatography, Liquid / Q000379:methods; D007783:Lactones / Q000737:chemistry; D019787:Linoleic Acid / Q000737:chemistry; D015227:Lipid Peroxidation; D013058:Mass Spectrometry / Q000379:methods; D008956:Models, Chemical; D018384:Oxidative Stress; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: C403894:4-oxo-2-nonenal; D000447:Aldehydes; D015415:Biomarkers; D007783:Lactones; D019787:Linoleic Acid; D002251:Carbon Tetrachloride; C027576:4-hydroxy-2-nonenal; D000111:Acetylcysteine