title: Observation of cerebral metabolites in an animal model of acute liver failure in vivo: a 1H and 31P nuclear magnetic resonance study.
abstract: Acute liver failure was induced in rats by a single intragastric dose of carbon tetrachloride. This causes hepatic centrilobular necrosis, as indicated by histological examinations, and produces a large increase in the activity of serum alanine aminotransferase. The plasma NH4+ level (mean +/- SEM) was 123 +/- 10 microM in the control group and 564 +/- 41 microM in animals with acute liver failure (each n = 5). 31P nuclear magnetic resonance (NMR) was used to monitor brain cortical high-energy phosphate compounds, Pi, and intracellular pH. 1H NMR spectroscopy was utilised to detect additional metabolites, including glutamate, glutamine, and lactate. The results show that the forebrain is capable of maintaining normal phosphorus energy metabolite ratios and intracellular pH despite the metabolic challenge by an elevated blood NH4+ level. There was a significant increase in the brain glutamine level and a concomitant decrease in the glutamate level during hyperammonaemia. The brain lactate level increased twofold in rats with acute liver failure. The results indicate that 1H NMR can be used to detect cerebral metabolic changes in this model of hyperammonaemia, and our observations are discussed in relation to compartmentation of NH4+ metabolism.
authors.affiliation: Department of Physics in Relation to Surgery, Hunterian Institute, Royal College of Surgeons of England, London.
authors.forename: T E
authors.initials: TE
authors.lastname: Bates
authors.forename: S R
authors.initials: SR
authors.lastname: Williams
authors.forename: R A
authors.initials: RA
authors.lastname: Kauppinen
authors.forename: D G
authors.initials: DG
authors.lastname: Gadian
mesh_terms: D000208:Acute Disease; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D005973:Glutamine / Q000378:metabolism; D006859:Hydrogen; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008107:Liver Diseases / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010758:Phosphorus / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D015415:Biomarkers; D005971:Glutamates; D007773:Lactates; D005973:Glutamine; D010758:Phosphorus; D019344:Lactic Acid; D018698:Glutamic Acid; D006859:Hydrogen