Treatment of ammonia intoxication in rats through the use of amino acids from the urea cycle.
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.
Ortolani
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EL
Department of Clinical Sciences, College of Veterinary Medicine, University of Sao Paulo, Brazil.
Marcondes
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MC
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*
D000085:Acetates; D007656:Ketoglutaric Acids; D002956:Citrulline; D014508:Urea; D001120:Arginine; D009952:Ornithine; C018824:ammonium acetate