title: Treatment of ammonia intoxication in rats through the use of amino acids from the urea cycle.
abstract: To evaluate the effectiveness of the treatment of severe ammonia intoxication with amino acids from the urea cycle (arginine, citrulline and ornithine) and alpha-ketoglutarate, 371 rats were used. The rats were poisoned with a lethal ip dose (99.9%) of ammonium acetate. Five min later they were treated with bidistilled water (control) or with standard urea-cycle mixed amino acid solutions containing 2, 4 or 6 mM arginine/kg bw as the marker basic amino acid or 2 mM arginine + 4 mM alpha-ketoglutarate/kg bw. The clinical picture and plasma urea concentration were followed. All 4 treatment groups had higher survival rates (20.83%-35.71%) than did the controls (1.18%). Surviving animals had a less severe clinical picture and presented fewer convulsive episodes than did fatally-poisoned rats. The higher doses of arginine increased the mean survival time of rats which died. The overall mean plasma urea concentration in surviving rats was higher (75.1 +/- 10.8 mg/dL) than in fatally-poisoned rats (44.4 +/- 4.9 mg/dL). Treatment with urea-cycle amino acids increased hepatic detoxication of ammonia; however, there was no relationship between the doses used and survival rates. There was no apparent synergism between urea-cycle amino acids and alpha-ketoglutarate.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, University of Sao Paulo, Brazil.
authors.forename: E L
authors.initials: EL
authors.lastname: Ortolani
authors.forename: M C
authors.initials: MC
authors.lastname: Marcondes
mesh_terms: D000085:Acetates / Q000008:administration & dosage / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000627:therapeutic use*; D002956:Citrulline / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D007656:Ketoglutaric Acids / Q000378:metabolism / Q000627:therapeutic use*; D008297:Male; D009952:Ornithine / Q000627:therapeutic use*; D011041:Poisoning / Q000188:drug therapy / Q000401:mortality; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate; D014508:Urea / Q000097:blood*
chemical_list: D000085:Acetates; D007656:Ketoglutaric Acids; D002956:Citrulline; D014508:Urea; D001120:Arginine; D009952:Ornithine; C018824:ammonium acetate