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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

Linsheng Liu, Chenrong Huang, Yicong Bian, Liyan Miao
Biochemical and biophysical research communications 2017 pp. -
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
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.