Treatment of ammonia intoxication in rats through the use of amino acids from the urea cycle

Vet Hum Toxicol. 1995 Jun;37(3):217-20.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / administration & dosage
  • Acetates / toxicity*
  • Analysis of Variance
  • Animals
  • Arginine / therapeutic use*
  • Citrulline / therapeutic use*
  • Injections, Intraperitoneal
  • Ketoglutaric Acids / metabolism
  • Ketoglutaric Acids / therapeutic use*
  • Male
  • Ornithine / therapeutic use*
  • Poisoning / drug therapy
  • Poisoning / mortality
  • Rats
  • Rats, Wistar
  • Survival Rate
  • Urea / blood*

Substances

  • Acetates
  • Ketoglutaric Acids
  • Citrulline
  • Urea
  • Arginine
  • Ornithine
  • ammonium acetate