TitleMercapturic acid conjugates of 4-hydroxy-2-nonenal and 4-oxo-2-nonenal metabolites are in vivo markers of oxidative stress.
Publication TypeJournal Article
Year of Publication2008
AuthorsKuiper HC, Miranda CL, Sowell JD, Stevens JF
JournalJ Biol Chem
Date Published2008 Jun 20
KeywordsAcetylcysteine, Aldehydes, Animals, Biomarkers, Carbon Tetrachloride, Chromatography, Liquid, Lactones, Linoleic Acid, Lipid Peroxidation, Mass Spectrometry, Models, Chemical, Oxidative Stress, Rats, Rats, Inbred F344

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.

Alternate JournalJ. Biol. Chem.
PubMed ID18442969
PubMed Central IDPMC2427341
Grant ListS10 RR022589 / RR / NCRR NIH HHS / United States
P30ES000210 / ES / NIEHS NIH HHS / United States
S10RR022589 / RR / NCRR NIH HHS / United States
R01 HL081721 / HL / NHLBI NIH HHS / United States
R01HL081721 / HL / NHLBI NIH HHS / United States
P30 ES000210 / ES / NIEHS NIH HHS / United States