Journal
JOURNAL OF PROTEOME RESEARCH
Volume 19, Issue 10, Pages 4071-4081Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.0c00440
Keywords
ethanol; toxicity; metabolic phenotyping; metabolomics; LC-MS; brain; cerebral tissue
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Funding
- project Study of alcohol toxicity at chronic and acute alcohol consumption, discovery and evaluation of biomarkers by applying metabolomics based methods under the call for proposals Supporting researchers with emphasis on new researchers [5005029, EDULLL 34]
- European Union (European Social Fund (ESF)) by the Operational Programme Human Resources Development, Education and Lifelong Learning 2014-2020
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The chronic and acute effect of ethanol administration on the metabolic phenotype of mouse brain was studied in a C57BL/6 mouse model of ethanol abuse using both untargeted and targeted ultra performance liquid chromatography-tandem mass spectrometry. Two experiments based on either chronic (8 week) exposure to ethanol of both male and female mice or acute exposure of male mice for 11 days, plus 2 oral gavage doses of 25% ethanol, were undertaken. Marked differences were found in amino acids, nucleotides, nucleosides, and related metabolites as well as a number of different lipids. Using untargeted metabolite profiling, acute ethanol exposure found significant decreases in several metabolites including nucleosides, fatty acids, glycerophosphocholine, and a number of phospholipids, while chronic exposure resulted in increases in several amino acids with notable decreases in adenosine, acetylcarnitine, and galactosylceramides. Similarly, targeted metabolite analysis, focusing on the hydrophilic fraction of the brain tissue extract, identified significant decreases in the metabolism of amino acids and derivatives, as well as purine degradation especially after chronic exposure to ethanol.
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