Changes in hepatic nitrogen metabolism in isolated perfused liver during the development of thioacetamide-induced cirrhosis in rats

Changes in hepatic nitrogen metabolism in isolated perfused liver were stud ied during the induction of experimental cirrhosis by thioacetamide in fema le Sprague-Dawley rats. Cirrhosis of the micronodular type developed during 12-week administration of thioacetamide. Despite an increase in food consu mption for 4 weeks after the end of administration, the physiological chang es characteristic of cirrhosis were maintained. The rate of urea excretion per unit liver weight was significantly decreased compared with pair-fed co ntrol rats both during and after thioacetamide treatment. During 4 weeks of thioacetamide treatment, the rate of urea production in perfused liver fro m a combination of 0.25 mM NH4Cl and 1 mM glutamine decreased slightly, wit hout a decrease in the maximum rate of urea production from 10 mM NH4Cl. In cirrhotic rats, the rate of urea production in perfused liver from NH4Cl a nd/or glutamine decreased, with a decrease in the maximum rate of urea prod uction. The K-m of ureagenesis for NH3 was unchanged in cirrhotic livers. D uring 4 weeks of thioacetamide treatment, glutamate dehydrogenase activity decreased, but the thioacetamide-induced cirrhotic state had no effect on g lutamate dehydrogenase or glutaminase activity. Glutamine synthetase activi ty was decreased in rats treated with thioacetamide for 4 or 12 weeks. Thes e results are consistent with the hypothesis that the capacity for urea pro duction from NH3 and amino acids is decreased in the development of cirrhos is. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.