Increased serotoninergic and noradrenergic activity in hepatic encephalopathy in rats with thioacetamide—induced acute liver failure

Authors

  • Cihan Yurdaydin,

    1. First Department of Gastroenterology and Hepatology, University of Vienna, A-1090 Vienna, Austria
    Current affiliation:
    1. Liver Unit, NIH, NIDDK, Building 10, Room 4D 52, 9000 Rockville Pike, Bethesda MD 20892
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    • Cihan Yurdaydin was a visiting scientist from the University of Ankara, Turkey, supported by the “Österreichischer Auslandsstudentendienst”.

  • Heide Hörtnagl,

    1. Institute of Biochemical Pharmacology, University of Vienna, A-1090 Vienna, Austria
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  • Petra Steindl,

    1. First Department of Gastroenterology and Hepatology, University of Vienna, A-1090 Vienna, Austria
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  • Christof Zimmermann,

    1. First Department of Gastroenterology and Hepatology, University of Vienna, A-1090 Vienna, Austria
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  • Christian Pifl,

    1. Institute of Biochemical Pharmacology, University of Vienna, A-1090 Vienna, Austria
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  • Ernst A. Singer,

    1. Institute of Pharmacology, University of Vienna, A-1090 Vienna, Austria
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  • Erich Roth,

    1. First Department of Surgery, University of Vienna, A-1090 Vienna, Austria
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  • Peter Ferenci M.D.

    Corresponding author
    1. First Department of Gastroenterology and Hepatology, University of Vienna, A-1090 Vienna, Austria
    • First Department of Gastroenterology and Hepatology, University of Vienna, Lazarettgasse 14, A-1090 Vienna, Austria
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Abstract

Functional changes of various neurotransmitter systems have been implicated in the pathogenesis of hepatic encephalopathy. In this study the role of brain monoaminergic neurotransmitter systems in hepatic encephalopathy was investigated in rats with thioacetamide-induced acute liver failure. Concentrations of serotonin, dopamine, noradrenaline and of their metabolites 5-hydroxyindoleacetic acid, dihydroxyphenylalanine (following inhibition of dihydroxyphenylalanine-decarboxylase), dihydroxy-phenylacetic acid, homovanillic acid and 3-methoxy-4-hydroxyphenyl-glycol, were measured in the cerebral cortex, striatum and hippocampus by high performance liquid chromatography with electrochemical detection. In hepatic encephalopathy concentrations of 5-hydroxyindoleacetic acid were increased in all three brain areas (196%, 204% and 264% of salinetreated controls, p < 0.01), and concentrations of serotonin were increased in the frontal cortex (121%, p < 0.01). In the frontal cortex and hippocampus of encephalopathic rats dopamine levels were increased (157% and 289%, p < 0.05), and levels of noradrenaline (53% and 46%, p < 0.05) were decreased associated with increased 3-methoxy-4-hydroxyphenylglycol levels (173% and 206%, p < 0.05). The extent of these changes correlated with the stage of hepatic encephalopathy. In hepatic encephalopathy dihydroxyphenylalanine accumulation was increased in the hippocampus and unchanged in the cerebral cortex. Dopamine, noradrenaline, dihydroxyphenylacetic acid and homovanillic acid concentrations were unchanged in the striatum. The results of this study indicate that hepatic encephalopathy in thioacetamide-induced acute liver failure in rats is associated with neurochemical changes, suggesting an increased activity of the noradrenergic and serotoninergic neurotransmitter systems. (HEPATOLOGY 1990;12:695–700).

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