Mixture of N-carbamoyl-L-glutamate plus L-arginine can protect rats with liver cirrhosis from acute ammonia intoxication

J Hepatol. 2001 Dec;35(6):719-25. doi: 10.1016/s0168-8278(01)00199-4.

Abstract

Background/aims: We earlier reported that N-carbamoyl-L-glutamate (CG) plus L-arginine (Arg) protected normal and 70% hepatectomized rats from intoxication by a lethal or sub-lethal dose of ammonium acetate, respectively. In the present study, the protective effect of these compounds on cirrhotic rats was assessed.

Methods: CG plus Arg were administered prior to the injection of a sub-lethal dose of ammonium acetate into dimethylnitrosamine-induced cirrhotic rats. Control rats were given phosphate-buffered saline (PBS) instead of the mixture. The behavior of the rats was monitored until the time of sacrifice. Blood ammonia level, blood urea nitrogen (BUN) and liver carbamoylphosphate synthetase I (CPS I) activity were determined.

Results: Pretreatment of rats with the mixture of CG plus Arg could significantly lower the blood ammonia level (P<0.05), increase the activity of CPS I (P<0.05), improve abnormal behavior associated with ammonia intoxication (P<0.05), and increase BUN (P<0.05), as compared with the PBS-injected control group. There were significantly close correlations between (1) the increase of CPS I activity; (2) the improvement of abnormal behavior; (3) the increase of BUN; and (4) the decrease of the blood ammonia level.

Conclusions: A mixture of CG plus Arg could protect rats with liver cirrhosis from acute ammonia intoxication.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / poisoning*
  • Acute Disease
  • Ammonia / blood
  • Animals
  • Arginine / pharmacology*
  • Behavior, Animal / drug effects
  • Carbamoyl-Phosphate Synthase (Ammonia) / metabolism
  • Dimethylnitrosamine
  • Drug Synergism
  • Glutamates / pharmacology*
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / drug therapy*
  • Male
  • Poisoning / prevention & control
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors

Substances

  • Acetates
  • Glutamates
  • N-carbamylglutamate
  • Ammonia
  • Arginine
  • Carbamoyl-Phosphate Synthase (Ammonia)
  • Dimethylnitrosamine
  • ammonium acetate