title: Metabonomic analysis of liver tissue from BALB/c mice with D-galactosamine/lipopolysaccharide-induced acute hepatic failure.
abstract: 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.
authors.affiliation: Hepatology Institute, Peking University People's Hospital, No 11 Xizhimen South Street, Beijing 100044, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Feng
authors.forename: Shengming
authors.initials: S
authors.lastname: Wu
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
authors.forename: Fangting
authors.initials: F
authors.lastname: Dong
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism*; D005688:Galactosamine; D008401:Gas Chromatography-Mass Spectrometry; D006539:Heptoses / Q000378:metabolism; D006601:Hexoses / Q000378:metabolism*; D008070:Lipopolysaccharides; D008099:Liver / Q000378:metabolism*; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D008320:Maltose / Q000378:metabolism; D055442:Metabolome; D055432:Metabolomics; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D000596:Amino Acids; D005227:Fatty Acids; D006539:Heptoses; D006601:Hexoses; D008070:Lipopolysaccharides; C003011:sedoheptulose; D008320:Maltose; D005688:Galactosamine