Identification of trans,trans-2,4-Decadienal Metabolites in Mouse and Human Cells Using Liquid Chromatography–Mass Spectrometry
| Autor: | Ming Hua Hsu, Pinpin Lin, Huei Ju Liu, Kao Lu Pan, Wei Jan Huang, Mei Ya Shen, Hui Ling Lee, Chia Wei Cheng, Ming-Hsien Tsai |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Cell Survival Toxicology Tandem mass spectrometry Mass spectrometry Cell Line Lipid peroxidation Mice chemistry.chemical_compound Isomerism Tandem Mass Spectrometry In vivo Liquid chromatography–mass spectrometry Animals Humans Cysteine Biotransformation Chromatography High Pressure Liquid Fomepizole Aldehydes Mice Inbred ICR Chromatography General Medicine Glutathione Triple quadrupole mass spectrometer Metabolic pathway Biochemistry chemistry Isotope Labeling Pyrazoles Oxidation-Reduction Biomarkers |
| Zdroj: | Chemical Research in Toxicology. 27:1707-1719 |
| ISSN: | 1520-5010 0893-228X |
| DOI: | 10.1021/tx500199b |
| Popis: | trans,trans-2,4-Decadienal (tt-DDE), a lipid peroxidation product of linolieic acid, is the most abundant aldehyde identified in cooking oil fumes and is readily detectable in food products as well as in restaurant emissions. Previously, we have reported the toxicological effects of tt-DDE in vitro and in vivo. However, the metabolic pathways of tt-DDE in vivo remain unclear. In our present study, we combined liquid chromatography-mass spectrometry with triple quadrupole and time-of-flight to identify tt-DDE metabolites in the urine of mice orally administered tt-DDE. We identified two tt-DDE metabolites, 2,4-decadienoic acid and cysteine-conjugated 2,4-decadien-1-ol, in the urine of mice gavaged with tt-DDE and in human hepatoma cell cultures. The structure of 2,4-decadienoic acid was confirmed upon comparison of its tandem mass spectrometry (MS/MS) spectrum and retention time with those of synthetic standards. The moieties of cysteine and alcohol on cysteine-conjugated 2,4-decadien-1-ol were validated by treating cell cultures with stable-isotope-labeled cysteine and 4-methylpyrazole, an alcohol dehydrogenase inhibitor. The MS/MS spectra of a cysteine standard and ionized cysteine detached from cysteine-conjugated 2,4-decadien-1-ol were identical. Two metabolic pathways for the biotransformation of tt-DDE in vivo are proposed: (i) the oxidation of tt-DDE to the corresponding carboxylic acid, 2,4-decadienoic acid, in liver cells and (ii) glutathione (GHS) conjugation, GSH breakdown, and aldehyde reduction, which generate cysteine-conjugated 2,4-decadien-1-ol in both liver and lung cells. In conclusion, this platform can be used to identify tt-DDE metabolites, and cysteine-conjugated 2,4-decadien-1-ol can serve as a biomarker for assessing exposure to tt-DDE. |
| Databáze: | OpenAIRE |
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