title: A urinary metabonomics study on biochemical changes in yeast-induced pyrexia rats: a new approach to elucidating the biochemical basis of the febrile response.
abstract: 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) ↑-hypothalamus Na⁺/Ca²⁺-cAMP↑" 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.
authors.affiliation: Science Experiment Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11, North Third Ring Road, Chaoyang District, Beijing 100029, PR China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Gao
authors.forename: Mingxing
authors.initials: M
authors.lastname: Guo
authors.forename: Baosheng
authors.initials: B
authors.lastname: Zhao
authors.forename: Long
authors.initials: L
authors.lastname: Peng
authors.forename: Jiankun
authors.initials: J
authors.lastname: Su
authors.forename: Xu
authors.initials: X
authors.lastname: Bai
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Yanjiang
authors.initials: Y
authors.lastname: Qiao
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000652:urine*; D005334:Fever / Q000652:urine*; D008297:Male; D013058:Mass Spectrometry; D055432:Metabolomics; D015999:Multivariate Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D014364:Tryptophan / Q000652:urine; D015003:Yeasts / Q000472:pathogenicity*
chemical_list: D015415:Biomarkers; D014364:Tryptophan