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

BMC Gastroenterology

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

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

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

Others  :  858031
DOI  :  10.1186/1471-230X-13-73

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

【 摘 要 】

Background

Compared 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).

Methods

After 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.

Results

Distinct 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.

Conclusions

GC/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】

   
2013 Feng et al.; licensee BioMed Central Ltd.

【 图 表 】

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