Metabolite profiling and pathway analysis of acute hepatitis rats by UPLC-ESI MS combined with pattern recognition methods

Xijun Wang*, Haitao Lv, Aihua Zhang, Wenjun Sun, Lian Liu, Ping Wang, Zeming Wu, Dixin Zou, Hui Sun

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

30 Citations (Scopus)


Background & Aims: Metabolomics is comprehensive analysis of low-molecular-weight endogenous metabolites in a biological sample. It could enable mapping of perturbations of early biochemical changes in diseases and hence provide an opportunity to develop predictive biomarkers that could provide valuable insights into the mechanisms of diseases. The aim of this study was to elucidate the changes in endogenous metabolites and to phenotype the metabolic profiling of d-galactosamine (GalN)-inducing acute hepatitis in rats by UPLC-ESI MS. 

Methods: The systemic biochemical actions of GalN administration (ip, 400 mg/kg) have been investigated in male wistar rats using conventional clinical chemistry, liver histopathology and metabolomic analysis of UPLC- ESI MS of urine. The urine was collected predose (-24 to 0 h) and 0-24, 24-48, 48-72, 72-96 h post-dose. Mass spectrometry of the urine was analysed visually and via conjunction with multivariate data analysis. 

Results: Results demonstrated that there was a time-dependent biochemical effect of GalN dosed on the levels of a range of low-molecular-weight metabolites in urine, which was correlated with developing phase of the GalN-inducing acute hepatitis. Urinary excretion of beta-hydroxybutanoic acid and citric acid was decreased following GalN dosing, whereas that of glycocholic acid, indole-3-acetic acid, sphinganine, n-acetyl-l-phenylalanine, cholic acid and creatinine excretion was increased, which suggests that several key metabolic pathways such as energy metabolism, lipid metabolism and amino acid metabolism were perturbed by GalN. 

Conclusion: This metabolomic investigation demonstrates that this robust non-invasive tool offers insight into the metabolic states of diseases.

Original languageEnglish
Pages (from-to)759-770
Number of pages12
JournalLiver International
Issue number5
Early online date2 Aug 2013
Publication statusPublished - May 2014

Scopus Subject Areas

  • Hepatology

User-Defined Keywords

  • D-galactosamine
  • Hepatitis
  • Metabolite
  • Metabolomics
  • Pattern recognition methods


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