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

Wang, Xijun, Lu, Haitao, Zhang, Aihua, Sun, Wenjun, Liu, Lian, Wang, Ping, Wu, Zeming, Zou, Dixin, & Sun, Hui (2014) Metabolite profiling and pathway analysis of acute hepatitis rats by UPLC-ESI MS combined with pattern recognition methods. Liver International, 34(5), pp. 759-770.

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Abstract

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.

Impact and interest:

5 citations in Scopus
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3 citations in Web of Science®

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ID Code: 62373
Item Type: Journal Article
Refereed: Yes
Additional Information: Wang, Xijun
Lv, Haitao
Zhang, Aihua
Sun, Wenjun
Liu, Lian
Wang, Ping
Wu, Zeming
Zou, Dixin
Sun, Hui
Liver Int. 2013 Aug 2. doi: 10.1111/liv.12301.
Keywords: D-galactosamine;hepatitis;metabolite;metabolomics;pattern recognition methods;UPLC-ESI MS
DOI: 10.1111/liv.12301
ISSN: 1478-3231
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2013 John Wiley & Sons A/S
Deposited On: 09 Sep 2013 05:03
Last Modified: 01 Sep 2014 23:38

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