Mixture of N-carbamoyl-L-glutamate plus L-arginine can protect rats with liver cirrhosis from acute ammonia intoxication.
OBJECTIVE
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.
Kim
W H
WH
Department of General Surgery, Ajou University School of Medicine, 442-749, Suwon, South Korea.
Park
H
H
Yun
C
C
Cho
H
H
Kim
S
S
Paik
W K
WK
Jeon
S H
SH
Lee
J H
JH
D000085:Acetates / Q000506:poisoning*; D000208:Acute Disease; D000641:Ammonia / Q000097:blood; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002222:Carbamoyl-Phosphate Synthase (Ammonia) / Q000378:metabolism; D004128:Dimethylnitrosamine; D004357:Drug Synergism; D005971:Glutamates / Q000494:pharmacology*; D008103:Liver Cirrhosis / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D011041:Poisoning / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000085:Acetates; D005971:Glutamates; C006895:N-carbamylglutamate; D000641:Ammonia; D001120:Arginine; D002222:Carbamoyl-Phosphate Synthase (Ammonia); D004128:Dimethylnitrosamine; C018824:ammonium acetate