title: Chronic hyperammonemia prevents changes in brain energy and ammonia metabolites induced by acute ammonium intoxication.
abstract: Acute ammonia toxicity has been attributed to the depletion of energy metabolite intermediates. Ingestion of an ammonium containing diet produces hyperammonemia and protects rats against acute ammonium intoxication. We have tested the effect of chronic hyperammonemia on the brain contents of energy and ammonia metabolite intermediates and on the effect on these contents of acute ammonia intoxication (i.p. injection of 7 mmol/kg of ammonium acetate). Chronic hyperammonemia was induced in rats by feeding them a diet containing 20% ammonium acetate. Control rat were fed the same diet without addition of ammonium acetate. It is shown that chronic hyperammonemia did not affect the content of most metabolites, the only remarkable changes are the increases of the contents of ammonia (46%), glutamine (81%), acetoacetate (31%) and of the mitochondrial NAD+/NADH ratio (32%) as well as the marked decrease of beta-hydroxybutyrate (by 86%). Chronic hyperammonemia prevents most changes in metabolites induced by acute ammonium intoxication (i.p. injection of 7 mmol/kg of ammonium acetate). In control rats it was a marked breakdown of glycogen and increased contents of glucose, lactate and pyruvate, with decreased cytosolic NAD+/NADH ratio and beta-hydroxybutyrate and ATP contents. These changes were nearly completely prevented in hyperammonemic rats. In controls, ammonia increased 12.8-fold while glutamate and aspartate decreased by approximately 40% and glutamine and alanine raised by 37% and 93%, respectively; in hyperammonemic rats ammonia increased 6.9-fold while glutamate, glutamine and alanine were not significantly affected. Also the mitochondrial NAD+/NADH ratio raised by 18-fold in controls and by 6-fold in hyperammonemic rats. These results indicate that chronic hyperammonemia markedly prevents the alterations of the contents of energy and ammonia metabolites induced by acute ammonium intoxication.
authors.affiliation: Instituto de Investigaciones Citológicas de la Fundación Valenciana de Investigaciones Biomédicas, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Kosenko
authors.forename: Y G
authors.initials: YG
authors.lastname: Kaminsky
authors.forename: V
authors.initials: V
authors.lastname: Felipo
authors.forename: M D
authors.initials: MD
authors.lastname: Miñana
authors.forename: S
authors.initials: S
authors.lastname: Grisolía
mesh_terms: D000641:Ammonia / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004032:Diet; D004734:Energy Metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000641:Ammonia