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

Authors

  • Xijun Wang,

    Corresponding author
    1. National TCM Key Lab of Serum Pharmacochemistry, Key Lab of Chinmedomics, and Key Pharmacometabolomics Platform of Chinese Medicines, Heilongjiang University of Chinese Medicine, Harbin, China
    • Correspondence

      Xijun Wang, National TCM Key Lab of Serum Pharmacochemistry, Key Lab of Chinmedomics, Key Pharmacometabolomics Platform of Chinese Medicines, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China

      Tel. & Fax: +86 451 8219 3039

      e-mail: metabolomics@126.com

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  • Haitao Lv,

    1. National TCM Key Lab of Serum Pharmacochemistry, Key Lab of Chinmedomics, and Key Pharmacometabolomics Platform of Chinese Medicines, Heilongjiang University of Chinese Medicine, Harbin, China
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  • Aihua Zhang,

    1. National TCM Key Lab of Serum Pharmacochemistry, Key Lab of Chinmedomics, and Key Pharmacometabolomics Platform of Chinese Medicines, Heilongjiang University of Chinese Medicine, Harbin, China
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  • Wenjun Sun,

    1. National TCM Key Lab of Serum Pharmacochemistry, Key Lab of Chinmedomics, and Key Pharmacometabolomics Platform of Chinese Medicines, Heilongjiang University of Chinese Medicine, Harbin, China
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  • Lian Liu,

    1. National TCM Key Lab of Serum Pharmacochemistry, Key Lab of Chinmedomics, and Key Pharmacometabolomics Platform of Chinese Medicines, Heilongjiang University of Chinese Medicine, Harbin, China
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  • Ping Wang,

    1. National TCM Key Lab of Serum Pharmacochemistry, Key Lab of Chinmedomics, and Key Pharmacometabolomics Platform of Chinese Medicines, Heilongjiang University of Chinese Medicine, Harbin, China
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  • Zeming Wu,

    1. National TCM Key Lab of Serum Pharmacochemistry, Key Lab of Chinmedomics, and Key Pharmacometabolomics Platform of Chinese Medicines, Heilongjiang University of Chinese Medicine, Harbin, China
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  • Dixin Zou,

    1. National TCM Key Lab of Serum Pharmacochemistry, Key Lab of Chinmedomics, and Key Pharmacometabolomics Platform of Chinese Medicines, Heilongjiang University of Chinese Medicine, Harbin, China
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  • Hui Sun

    1. National TCM Key Lab of Serum Pharmacochemistry, Key Lab of Chinmedomics, and Key Pharmacometabolomics Platform of Chinese Medicines, Heilongjiang University of Chinese Medicine, Harbin, China
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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.

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