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Vol. 21, Art. 88 (pp. 1134-1156)    |    2020       

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Hepatoencephalopathy: the role of cerebral ammonia-forming reactions

Institute of Theoretical and Experimental Biophysics of Russian Academy of Sciences, Pushchino, Russia
Hospital Clinico Research Foundation. INCLIVA Health Research Institute, Valencia, Spain
Pathology Department, Faculty of Medicine, University of Valencia, Valencia, Spain

Brief summary

Hepatoencephalopathy (HE) is a dysfunction of the brain that occurs in patients with progressive liver failure. Conceptually, the main reason for the development of HE is the accumulation of ammonia in the brain due to impaired liver detoxification pathways associated with hepatocyte damage, or the formation of portocaval anastomoses. However, an increase in the concentration of ammonia in the brain, observed in various pathologies when its level in the blood lies in the normal range and the detoxification function of the liver is preserved, indicates that ammonia is not only transported to the brain from the blood, but is generated in the brain as a result of activation of intracellular ammonia-forming reactions. This research has been conducted with the goal to identify possible sources of ammonia in the brain. So, we performed a comparative analysis of the state of the enzymatic systems responsible for the maintenance of ammonia homeostasis in different parts of the rat brain and the effect of the known convulsants of ammonium acetate and pentylenetetrazolium on these systems. The activities of adenosine deaminase, AMP deaminase, glutamine synthetase, glutamate dehydrogenase, glutaminase, aspartate aminotransferase and alanine aminotransferase were studied in various subcellular fractions isolated from different regions of the rat brain after the development of seizures caused by the administration of both convulsants. It was shown that both ammonium acetate and pentylenetetrazolium are able to enhance endogenous ammonia-forming reactions in mitochondria and cytosol of different parts of the brain, regardless of the concentration of ammonia in the blood and the detoxification function of the liver, and can independently contribute to its significant accumulation in the brain and the development of encephalopathy and convulsive symptoms.


Key words

ammonia-metabolizing enzymes, hyperammonemia, neocortex, cerebellum, hippocampus, striatum, liver.

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