Metabonomic analysis of liver tissue from BALB/c mice with d-galactosamine/lipopolysaccharide-induced acute hepatic failure

BMC Gastroenterology

Research Article

Lai Wei¹  Bo Feng¹  Feng Liu¹  Yan Gao¹  Fangting Dong²  Shengming Wu² 

[1] Hepatology Institute, Peking University People’s Hospital, No.11 Xizhimen South Street, 100044, Beijing, P.R. China;National Center of Biomedical Analysis, No.27 Taiping Road, 100039, Beijing, P.R. China;

关键词: Acute liver failure;    Metabonomics;    GC/MS;    Liver tissue;   

DOI  :  10.1186/1471-230X-13-73

 received in 2012-07-12, accepted in 2013-04-22,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundCompared with biofluids, target tissues and organs more directly reflect the pathophysiological state of a disease process. In this study, a D-galactosamine (GalN) / lipopolysaccharide (LPS)-induced mouse model was constructed to investigate metabonomics of liver tissue and directly characterize metabolic changes in acute liver failure (ALF).MethodsAfter pretreatment of liver tissue, gas chromatography coupled to time-of-flight mass spectrometry (GC/TOFMS) was used to separate and identify the liver metabolites. Partial least squares – discriminant analysis models were constructed to separate the ALF and control groups and to find those compounds whose liver levels differed significantly between the two groups.ResultsDistinct clustering was observed between the ALF and control mice. Fifty-eight endogenous metabolites were identified. Compared with the control mice, many metabolites, including sugars, amino acids, fatty acids, and organic acids, underwent significant changes in the ALF group, some of which differed from changes observed in plasma. Significant reduction of some important intermediate metabolites indicates that production of ketone bodies, the tricarboxylic acid and urea cycles, gluconeogenesis, glycolysis and pentose phosphate pathways are inhibited after GalN/LPS administration.ConclusionsGC/TOFMS can be a powerful technique to perform metabonomic studies of liver tissue. GalN/LPS treatment can severely disturb substance metabolism in the liver, with different effects on metabolites compared with those observed in the plasma.

【 授权许可】

Unknown   
© Feng et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.