Dynamic changes of plasma metabolites in pigs with GalN-induced acute liver failure using GC-MS and UPLC-MS

Biomed Pharmacother. 2017 Sep:93:480-489. doi: 10.1016/j.biopha.2017.06.049. Epub 2017 Jun 30.

Abstract

Metabolomics facilitates investigation of the mechanisms of disease and screening for biomarkers. Here, a gas chromatography-mass spectrometry (GC-MS) and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)-based metabolomics approach was employed to identify plasma biomarkers of acute liver failure (ALF) in pigs. Blood was collected from pigs at 12h intervals during ALF. Hepatic injury was quantified by determining liver function and histopathology. Based on a multivariate data matrix and pattern recognition, two upregulated metabolites, namely, amino acids and conjugated bile acids, and two downregulated metabolites, lysophosphatidylcholines (LPCs) and phosphatidylcholines (PCs), were identified. All of these metabolites showed a strong relationship with the extent of liver injury. Amino acids were biomarkers of the severity of liver impairment, conjugated bile acids were predictive of early stage liver damage, and LPCs and PCs were related to the prognosis of liver injury. In conclusion, our results demonstrated the occurrence of marked metabolic disturbances during ALF and that integrated metabolomics analysis facilitates identification of biomarkers of disease.

Keywords: Acute liver failure; Biomarkers; GC–MS; Metabolomics; UPLC–MS.

MeSH terms

  • Animals
  • Biomarkers / blood
  • Chromatography, High Pressure Liquid / methods*
  • Galactosamine
  • Gas Chromatography-Mass Spectrometry / methods*
  • Liver / pathology
  • Liver Failure, Acute / blood*
  • Liver Failure, Acute / chemically induced
  • Liver Failure, Acute / metabolism*
  • Liver Failure, Acute / pathology
  • Metabolic Networks and Pathways
  • Metabolome*
  • Metabolomics
  • Multivariate Analysis
  • Sus scrofa

Substances

  • Biomarkers
  • Galactosamine