title: Acute liver failure in rats activates glutamine-glutamate cycle but declines antioxidant enzymes to induce oxidative stress in cerebral cortex and cerebellum.
abstract: OBJECTIVE
  Liver dysfunction led hyperammonemia (HA) causes a nervous system disorder; hepatic encephalopathy (HE). In the brain, ammonia induced glutamate-excitotoxicity and oxidative stress are considered to play important roles in the pathogenesis of HE. The brain ammonia metabolism and antioxidant enzymes constitute the main components of this mechanism; however, need to be defined in a suitable animal model. This study was aimed to examine this aspect in the rats with acute liver failure (ALF).
  
  
  METHODS
  ALF in the rats was induced by intraperitoneal administration of 300 mg thioacetamide/Kg. b.w up to 2 days. Glutamine synthetase (GS) and glutaminase (GA), the two brain ammonia metabolizing enzymes vis a vis ammonia and glutamate levels and profiles of all the antioxidant enzymes vis a vis oxidative stress markers were measured in the cerebral cortex and cerebellum of the control and the ALF rats.
  
  
  RESULTS
  The ALF rats showed significantly increased levels of ammonia in the blood (HA) but little changes in the cortex and cerebellum. This was consistent with the activation of the GS-GA cycle and static levels of glutamate in these brain regions. However, significantly increased levels of lipid peroxidation and protein carbonyl contents were consistent with the reduced levels of all the antioxidant enzymes in both the brain regions of these ALF rats.
  
  
  CONCLUSIONS
  ALF activates the GS-GA cycle to metabolize excess ammonia and thereby, maintains static levels of ammonia and glutamate in the cerebral cortex and cerebellum. Moreover, ALF induces oxidative stress by reducing the levels of all the antioxidant enzymes which is likely to play important role, independent of glutamate levels, in the pathogenesis of acute HE.
authors.affiliation: Department of Zoology, Guru Ghasidas Vishwavidyalaya, Bilaspur, Chhattisgarh, India.
authors.forename: Santosh
authors.initials: S
authors.lastname: Singh
authors.affiliation: Biochemistry and Molecular Biology Laboratory, Department of Zoology, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
authors.forename: Papia
authors.initials: P
authors.lastname: Mondal
authors.affiliation: Biochemistry and Molecular Biology Laboratory, Department of Zoology, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
authors.forename: Surendra K
authors.initials: SK
authors.lastname: Trigun
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism; D002531:Cerebellum / Q000201:enzymology*; D002540:Cerebral Cortex / Q000201:enzymology*; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D017114:Liver Failure, Acute / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D053858:Metabolic Networks and Pathways; D009928:Organ Specificity; D018384:Oxidative Stress; D050050:Protein Carbonylation; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D005973:Glutamine; D018698:Glutamic Acid; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005978:Glutathione
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