TitleQuantitation of mercapturic acid conjugates of 4-hydroxy-2-nonenal and 4-oxo-2-nonenal metabolites in a smoking cessation study.
Publication TypeJournal Article
Year of Publication2010
AuthorsKuiper HC, Langsdorf BL, Miranda CL, Joss J, Jubert C, Mata JE, Stevens JF
JournalFree Radic Biol Med
Date Published2010 Jan 01
KeywordsAcetylcysteine, Adolescent, Adult, Aged, Aldehydes, Female, Humans, Male, Middle Aged, Oxidative Stress, Reference Values, Smoking Cessation, Young Adult

The breakdown of polyunsaturated fatty acids (PUFAs) under conditions of oxidative stress results in the formation of lipid peroxidation (LPO) products. These LPO products such as 4-hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE) can contribute to the development of cardiovascular and neurodegenerative diseases and cancer. Conjugation with glutathione, followed by further metabolism to mercapturic acid (MA) conjugates, can mitigate the effects of these LPO products in disease development by facilitating their excretion from the body. We have developed a quantitative method to simultaneously assess levels of 4-oxo-2-nonen-1-ol (ONO)-MA, HNE-MA, and 1,4-dihydroxy-2-nonene (DHN)-MA in human urine samples utilizing isotope-dilution mass spectrometry. We are also able to detect 4-hydroxy-2-nonenoic acid (HNA)-MA, 4-hydroxy-2-nonenoic acid lactone (HNAL)-MA, and 4-oxo-2-nonenoic acid (ONA)-MA with this method. The detection of ONO-MA and ONA-MA in humans is significant because it demonstrates that HNE/ONE branching occurs in the breakdown of PUFAs and suggests that ONO may contribute to the harmful effects currently associated with HNE. We were able to show significant decreases in HNE-MA, DHN-MA, and total LPO-MA in a group of seven smokers upon smoking cessation. These data demonstrate the value of HNE and ONE metabolites as in vivo markers of oxidative stress.

Alternate JournalFree Radic. Biol. Med.
PubMed ID19819328
PubMed Central IDPMC2818256
Grant ListS10 RR022589 / RR / NCRR NIH HHS / United States
P30ES000210 / ES / NIEHS NIH HHS / United States
R01 HL081721-04 / HL / NHLBI NIH HHS / United States
S10RR022589 / RR / NCRR NIH HHS / United States
R01 HL081721 / HL / NHLBI NIH HHS / United States
S10 RR022589-010003 / RR / NCRR NIH HHS / United States
P30 ES000210-41 / ES / NIEHS NIH HHS / United States
R01HL081721 / HL / NHLBI NIH HHS / United States
P30 ES000210 / ES / NIEHS NIH HHS / United States