PT - JOURNAL ARTICLE AU - Rolf Gebhardt AU - Gerhard Beckers AU - Frank Gaunitz AU - Wolfram Haupt AU - Dirk Jonitza AU - Sabine Klein AU - Ludger Scheja TI - 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 DP - 1997 Oct 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 1--6 VI - 283 IP - 1 4099 - http://jpet.aspetjournals.org/content/283/1/1.short 4100 - http://jpet.aspetjournals.org/content/283/1/1.full SO - J Pharmacol Exp Ther1997 Oct 01; 283 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