UPLC-MS-based serum metabonomics for identifying acute liver injury biomarkers in Chinese miniature pigs

Abstract

Metabonomics has emerged as an important technology for exploring the underlying mechanisms of diseases and screening for biomarkers. In this investigation, to comprehensively assess metabolite changes in D-galactosamine (GalN)-induced liver injury in Chinese miniature pigs and to increase our understanding of physiological changes in normal and pathological states, we used ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) to analyze metabolites and identify biomarkers in serum. Blood samples were collected both from 18 h after GalN treatment group and control group pigs. We performed multivariate analyses on the metabolite profiles to identify potential biomarkers of acute liver injury, which were then confirmed by tandem MS. Based on "variable of importance in the project" (VIP) values and S-plots, four groups of biomarkers were identified--namely conjugated bile acids, lysophosphatidylcholines (LPCs), phosphatidylcholines (PCs) and fatty acid amides (FAAs)--that were present at significantly different levels in the control and GalN-induced groups. LPCs, PCs, and FAAs showed marked decreases in the GalN-treated group, whereas conjugated bile acids in the treated group showed considerable increases. Taken together, our results suggested that obvious metabolic disturbances occur during acute liver injury, which provided novel insights into the molecular mechanism(s) of D-galactosamine (GalN)-induced liver injury, and will facilitate future research and management of liver injury.

Keywords: Acute liver injury; Biomarker; Metabonomics; UPLC-MS.