RT Journal Article
SR Electronic
T1 Treatment of Cirrhotic Rats with<span class="sc">l</span>-Ornithine-<span class="sc">l</span>-Aspartate Enhances Urea Synthesis and Lowers Serum Ammonia Levels
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1
OP 6
VO 283
IS 1
A1 Rolf Gebhardt
A1 Gerhard Beckers
A1 Frank Gaunitz
A1 Wolfram Haupt
A1 Dirk Jonitza
A1 Sabine Klein
A1 Ludger Scheja
YR 1997
UL http://jpet.aspetjournals.org/content/283/1/1.abstract
AB CCl4-induced cirrhosis of rats was used for studying the influence of l-ornithine-l-aspartate (OA) on hyperammonemia. OA given to cirrhotic rats (2 g/kg daily) for 2 wk slightly increased net body weight and led to a significant increase in plasma urea levels and a decrease in plasma ammonia levels. Serum concentrations of glutamate, glutamine and arginine decreased significantly. In the livers of the OA-treated rats the activities of carbamoylphosphate synthetase I and arginase increased by 30 and 40%, respectively, approaching normal levels. No change in the activities of the other urea cycle enzymes as well as of glutamate dehydrogenase, glutaminase and glutamine synthetase was found. The negative correlation between glutamine synthetase activity and plasma ammonia levels reported previously for cirrhotic rats (Gebhardt and Reichen, Hepatology 20:684–691, 1994) was corroborated for cirrhotic animals not treated with OA, but was no longer apparent in OA-treated cirrhotic rats. Despite this improvement, plasma ammonia levels still varied considerably reflecting the variable accessibility and activities of glutamine synthetase in cirrhotics. Cultured hepatocytes from the two groups of rats showed a similar stimulation of urea production by addition of ammoniumacetate and/or OA to Hanks’ buffered salt solution. In Williams medium E, however, the hepatocytes from the OA group produced significantly more urea than those from controls. These results suggest that treatment of cirrhotic rats with OA considerably improves urea production favoring the detoxification of ammonia that, however, is still limited by the severe alterations in liver architecture that are not influenced by OA in a 2-wk period. The American Society for Pharmacology and Experimental Therapeutics