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GC-MS based metabolomics of CSF and blood serum: Metabolic phenotype for a rat model of cefoperazone-induced disulfiram-like reaction

Author:
Linsheng Liu, Chenrong Huang, Yicong Bian, Liyan Miao
Source:
Biochemical and biophysical research communications 2017 pp. -
ISSN:
0006-291X
Subject:
alanine, alcohols, animal models, aspartic acid, blood serum, carbohydrates, cefoperazone, cerebrospinal fluid, citrates, energy metabolism, gas chromatography-mass spectrometry, glutamic acid, ingestion, leucine, metabolites, metabolomics, phenotype, pyruvic acid, rats, synaptic transmission, tricarboxylic acid cycle, valine
Abstract:
Cefoperazone is most popularly used in the treatment of complicated infections clinically. Concomitant ingestion of ethnaol and cefoperazone may cause a disulfiram-like reaction. However, very little is known about the possible interactions between cefoperazone treatment and an alcohol with regard to the induction of disulfiram-like reaction. Study of the metabolic impact of cotreatment with cefoperazone and alcohol on animals can facilitate the identification of markers relevant to disulfiram-like reaction. In this study, the serum and cerebrospinal fluid (CSF) metabolites from Sprague-Dawley rats were profiled using gas chromatography mass spectrometry. Serum levels of valine, leucine, glycine, palmitelaidic acid, and 2-hydroxyisobutyrate in combination application group were significantly higher than those in the control; while alanine and pyruvate deceased in cotreatment group. Most TCA intermediates, glutamate and aspartate had lower CSF level in combination application group, except citrate. In addition, most carbohydrates, ethylmalonate and N-acetylaspartate had higher level compared with control group. These results highlight concomitant ingestion of alcohol and cefoperazone generated disulfiram-like reaction by way of disrupting normal metabolic pathway. Cefoperazone magnifes ethanol-induced impairment of TCA cycle and aspartate metabolism, thereby affects energy metabolism and neural transmission.
Agid:
5701065