A urinary metabonomics study on biochemical changes in yeast-induced pyrexia rats: A new approach to elucidating the biochemical basis of the febrile response

详细信息    查看全文

• 作者：Xiaoyan Gao^a ; Mingxing Guo^a ; Baosheng Zhao^a ; Long Peng^a ; Jiankun Su^a ; Xu Bai^b ; Jun Li^c ; Yanjiang Qiao^d ; ^{yjqiao@163.net}
• 关键词：Metabonomics ; Tryptophan metabolism ; Yeast-induced pyrexia ; Ultra performance liquid chromatography ; MSE
• 刊名：Chemico-Biological Interactions
• 出版年：2013
• 出版时间：25 June, 2013
• 年：2013
• 卷：204
• 期：1
• 页码：39-48
• 全文大小：1325 K

文摘

Fever is a prominent feature of many diseases, such as infection, inflammation and trauma. In the clinic, fever can be easily judged by measuring the body temperature; however, the pathogenesis of fever is still not fully understood. A febrile response is a systemic pathological process that can cause metabolic disorders. Metabonomics can provide powerful tools to reveal the pathological mechanisms for such a systemic disease. Thus, to reveal subtle metabolic changes under the condition of fever and to explore its mechanism, an ultra performance liquid chromatography coupled with a quadrupole time-of-flight mass spectrometry metabonomics approach was employed to investigate the urine biochemical characteristics of yeast-induced pyrexia rats. The acquired data were subjected to principal component analysis for differentiating the pyrexia rats from the control rats. Potential biomarkers were screened by using orthogonal partial least-squares-discriminant analysis and were identified by accurate mass, database, and MS/MS fragment information obtained from the MS^E technique. Sixteen metabolites in rat urine were identified as potential biomarkers. The relative intensities of the 15 potential biomarkers were calculated. The thermoregulatory circuitry of ¡°endogenous pyrogen (EP) ¡ü-hypothalamus Na⁺/Ca²⁺-cAMP¡ü¡± was partially confirmed in this study. The results suggested that UPLC/MS-based metabolic profiling of rat urine identifies impaired tryptophan metabolism as the mechanism of yeast-induced fever. This research provided informative data that the impaired tryptophan metabolism might be one of the important reasons in elucidating the biochemical basis of the febrile response.