title: Urinary metabonomics study on toxicity biomarker discovery in rats treated with Xanthii Fructus.
abstract: BACKGROUND
  Xanthii Fructus (XF) is commonly called "Cang-Erzi" in traditional Chinese medicine (TCM) and widely used for the treatment of sinusitis, headache, rheumatism, and skin itching. However, the clinical utilization of XF is relatively restricted owing to its toxicity.
  
  
  OBJECTIVE
  To discover the characteristic potential biomarkers in rats treated with XF by urinary metabonomics.
  
  
  METHODS
  Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was applied in the study. The total ion chromatograms obtained from control and different dosage groups were distinguishable by a multivariate statistical analysis method.
  
  
  RESULTS
  The greatest difference in metabolic profile was observed between high dosage group and control group, and the metabolic characters in rats treated with XF were perturbed in a dose-dependent manner. The metabolic changes in response for XF treatment were observed in urinary samples, which were revealed by orthogonal projection to latent structures discriminate analysis (OPLS-DA), and 10 metabolites could be served as the potential toxicity biomarkers. In addition, the mechanism associated with the damages of lipid per-oxidation and the metabolic disturbances of fatty acid oxidation were investigated.
  
  
  CONCLUSIONS
  These results indicate that metabonomics analysis in urinary samples may be useful for predicting the toxicity induced by XF.
authors.affiliation: Chinese Medicine Toxicological Laboratory, Institute of Traditional Chinese Medicine, Heilongjiang University of Chinese Medicine, Harbin 150040, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Lu
authors.forename: Min
authors.initials: M
authors.lastname: Cao
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
authors.forename: Xu-zhao
authors.initials: XZ
authors.lastname: Li
authors.forename: Hong-yu
authors.initials: HY
authors.lastname: Liu
authors.forename: Da-zhong
authors.initials: DZ
authors.lastname: Chen
authors.forename: Shu-min
authors.initials: SM
authors.lastname: Liu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000652:urine*; D002681:China; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000378:metabolism* / Q000633:toxicity*; D020834:Ethnopharmacology / Q000379:methods*; D005638:Fruit / Q000737:chemistry; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D013058:Mass Spectrometry; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D025341:Principal Component Analysis; D051381:Rats; D017208:Rats, Wistar; D031210:Xanthium / Q000737:chemistry*
chemical_list: D015415:Biomarkers; D004365:Drugs, Chinese Herbal
keywords: BPI; ESI; OPLS-DA; PCA; TCM; Toxicity biomarker; UPLC-QTOF-MS; Urinary metabonomics; XF; Xanthii Fructus; based peak intensity; electro-spray ionization; orthogonal projection to latent structures discriminate analysis; principal components analysis; traditional Chinese medicine; ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry