Abstract
Rats given 2 or 3 intraperitoneal injections of the hepatotoxin, thioacetamide (TAA), 250–300 mg/kg at 24h intervals, develop hepatocellular necrosis and the neurological syndrome of acute or subacute hepatic encephalopathy (HE), associated with extracellular accumulation of the excitatory amino acids glutamate (Glu) and aspartate (Asp) in different brain regions.1–6 We have continued to monitor this model for up to 21 days after the administration of TAA. The observations revealed that overt manifestations of HE and biochemical changes decreased as metabolic changes indicative of increased astrocytic metabolism occurred (increased activities of two astrocytic enzymes, glutamine synthetase and pyruvate carboxylase (PC), and enhanced immunoreactivity of glial fibrillary acidic protein [GFAP]).7 There was also a selective enhancement of the blood to brain transport (brain uptake index, BUI) of ornithine and taurine.8,9 On the other hand, light microscopic examination of the brains of rats 21 days after TAA treatment revealed widespread neuronal damage consistent with neurotoxicity associated with neuronal excitation.10 Also, HPLC analysis of extracellular amino acids in striatal microdialysates of TAA-treated rats revealed increased basal efflux of Glu and Asp and their amino acid metabolites glutamine (Gin) and alanine (Ala), and a decrease of basal taurine (Tau) efflux.7 The general picture emerging from these studies was that amelioration of HE was associated with an ongoing pathological process. We were interested in determining whether further evolution of the model will result in full recovery or a relapse.
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© 2003 Springer Science+Business Media Dordrecht
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Hilgier, W. et al. (2003). Long-term observations on rats with thioacetamide-induced hepatic failure. In: Jones, E.A., Meijer, A.J., Chamuleau, R.A.F.M. (eds) Encephalopathy and Nitrogen Metabolism in Liver Failure. Springer, Dordrecht. https://doi.org/10.1007/978-94-010-0159-5_14
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DOI: https://doi.org/10.1007/978-94-010-0159-5_14
Publisher Name: Springer, Dordrecht
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