GC-MS based metabolomics of CSF and blood serum: Metabolic phenotype for a rat model of cefoperazone-induced disulfiram-like reaction.
GC-MS based metabolomics of CSF and blood serum: Metabolic phenotype for a rat model of cefoperazone-induced disulfiram-like reaction.
复制标题
基于 GC-MS 的脑脊液和血清代谢组学：头孢哌酮诱导的双硫仑样反应大鼠模型的代谢表型。
DOI：
10.1016/j.bbrc.2017.06.167
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发表时间：
2017-08
期刊：
影响因子：
--
通讯作者：
Liyan Miao
中科院分区：
文献类型：
--
作者：
Linsheng Liu;Chenrong Huang;Yicong Bian;Liyan Miao
头孢哌酮是临床上治疗复杂感染最常用的药物。同时摄入乙醇和头孢哌酮可引起双硫仑样反应。然而，关于头孢哌酮治疗与酒精之间在诱导双硫仑样反应方面可能的相互作用，我们所知甚少。研究头孢哌酮与酒精联合治疗对动物代谢的影响，有助于识别与双硫仑样反应相关的标志物。本研究采用气相色谱-质谱法对Sprague-Dawley大鼠血清和脑脊液（CSF）代谢物进行了分析。联合用药组血清缬氨酸、亮氨酸、甘氨酸、棕榈酸、2-羟基异丁酸水平显著高于对照组；而联合治疗组丙氨酸和丙酮酸含量下降。除柠檬酸外，联合应用组的TCA中间体、谷氨酸和天冬氨酸的CSF水平均较低。此外，大多数碳水化合物、丙二酸乙酯和n -乙酰天冬氨酸水平均高于对照组。这些结果表明，同时摄入酒精和头孢哌酮通过破坏正常代谢途径产生双硫仑样反应。头孢哌酮加重乙醇诱导的TCA循环和天冬氨酸代谢损伤，从而影响能量代谢和神经传递。
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 andN-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.
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