Quantitation of mercapturic acid conjugates of 4-hydroxy-2-nonenal and 4-oxo-2-nonenal metabolites in a smoking cessation study |
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| Authors: | Heather C. Kuiper Brandi L. Langsdorf Cristobal L. Miranda Jacqueline Joss Carole Jubert John E. Mata Jan F. Stevens |
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| Affiliation: | 1. Linus Pauling Institute and the Department of Pharmaceutical Sciences, Oregon State University, Corvallis, OR 97331, USA;2. Pharmacy Department, Good Samaritan Regional Medical Center, Corvallis, OR 97330, USA;3. Department of Biomedical Sciences, Oregon State University, Corvallis, OR 97331, USA;1. School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China;2. Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China;3. Center for Developmental Therapeutics, Seattle Children''s Research Institute, Division of Gastroenterology and Hepatology, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98101, USA;1. School of Pharmacy, China Medical University, Shenyang 110001, PR China;2. College of Basic Medical Science, China Medical University, Shenyang 110001, PR China;1. Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy;2. Environmental and Industrial Toxicology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy;1. R.J. Reynolds Tobacco Co., 950 Reynolds Boulevard, Winston-Salem, NC 27105, United States;2. Carson Watts Consulting, 1266 Carson Watts Road, King, NC 27021, United States |
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| Abstract: | 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. |
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