title: A smaller initial dose protects mice against several lethal doses of ammonium acetate.
abstract: The synthesis of urea in the liver is the main mechanism for the elimination of excess ammonia. Rapid stimulation of the synthesis of urea (e.g. by administration of carbamyl glutamate, the analog of the physiological activator of carbamyl phosphate synthetase I) protects animals given lethal doses of ammonia. Since ammonia enhances the activity of the urea cycle, we tested and show here that administration of small doses of ammonium acetate supresses the mortality induced by a series of repeated LD100 of ammonium acetate separated by one hour, when the first LD100 is injected i.p. starting from 30 min to 5 hours after the initial smaller dose of ammonium acetate. Under these conditions, the levels of ammonia in blood are elevated more than ten times, but in spite of the greater amount of ammonia administered, the ammonemia is much lower than in mice dying after a single LD100. The enhanced synthesis of urea observed is correlated with an increase in the intramitochondrial content of N-acetyl glutamate. These findings are of interest as far as the short-term regulation of urea cycle, the mechanism of ammonia toxicity and have clinical implications.
authors.affiliation: Instituto de Investigaciones Citológicas de la Caja de Ahorros de Valencia, Centro Asociado del CSIC, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Costell
authors.forename: J E
authors.initials: JE
authors.lastname: O'Connor
authors.forename: S
authors.initials: S
authors.lastname: Grisolía
mesh_terms: D000085:Acetates / Q000008:administration & dosage / Q000633:toxicity*; D000641:Ammonia / Q000097:blood; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005971:Glutamates / Q000378:metabolism; D008297:Male; D051379:Mice; D008930:Mitochondria, Liver / Q000378:metabolism
chemical_list: D000085:Acetates; D005971:Glutamates; D000641:Ammonia; C016195:N-acetylglutamic acid; C018824:ammonium acetate