Identification of trans,trans-2,4-decadienal metabolites in mouse and human cells using liquid chromatography-mass spectrometry.

Abstract

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.

• Authors: Kao-Lu Pan, Wei-Jan Huang, Ming-Hua Hsu, Hui-Ling Lee, Huei-Ju Liu, Chia-Wei Cheng, Ming-Hsien Tsai, Mei-Ya Shen, Pinpin Lin
• Journal: Chemical research in toxicology (Chem Res Toxicol) Vol. 27 Issue 10 Pg. 1707-19 (Oct 20 2014) ISSN: 1520-5010 [Electronic] United States
• PMID: 25244621 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aldehydes
• Biomarkers
• Pyrazoles
• 2,4-decadienal
• Fomepizole
• Glutathione
• Cysteine

Topics

• Aldehydes (analysis, pharmacology, urine)
• Animals
• Biomarkers (analysis, urine)
• Biotransformation
• Cell Line
• Cell Survival (drug effects)
• Chromatography, High Pressure Liquid
• Cysteine (chemistry)
• Fomepizole
• Glutathione (chemistry, metabolism)
• Humans
• Isomerism
• Isotope Labeling
• Male
• Mice
• Mice, Inbred ICR
• Oxidation-Reduction
• Pyrazoles (chemistry)
• Tandem Mass Spectrometry