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

Department of Veterinary Physiology, College of Agriculture, Osaka Prefecture University, Japan.
Toxicology (Impact Factor: 3.62). 08/1999; 135(1):21-31. DOI: 10.1016/S0300-483X(99)00042-6
Source: PubMed


Changes in hepatic nitrogen metabolism in isolated perfused liver were studied during the induction of experimental cirrhosis by thioacetamide in female Sprague-Dawley rats. Cirrhosis of the micronodular type developed during 12-week administration of thioacetamide. Despite an increase in food consumption for 4 weeks after the end of administration, the physiological changes characteristic of cirrhosis were maintained. The rate of urea excretion per unit liver weight was significantly decreased compared with pair-fed control rats both during and after thioacetamide treatment. During 4 weeks of thioacetamide treatment, the rate of urea production in perfused liver from a combination of 0.25 mM NH4Cl and 1 mM glutamine decreased slightly, without 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 and/or glutamine decreased, with a decrease in the maximum rate of urea production. The Km of ureagenesis for NH3 was unchanged in cirrhotic livers. During 4 weeks of thioacetamide treatment, glutamate dehydrogenase activity decreased, but the thioacetamide-induced cirrhotic state had no effect on glutamate dehydrogenase or glutaminase activity. Glutamine synthetase activity was decreased in rats treated with thioacetamide for 4 or 12 weeks. These results are consistent with the hypothesis that the capacity for urea production from NH3 and amino acids is decreased in the development of cirrhosis.

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    • "Apesar da fibrose induzida com TAA se desenvolver mais lentamente do que com CCl 4 , o parênquima se torna completamente dividido por septos fibrosos bem demarcados (Shea e Manseau, 1968; Al-Bader et al., 2000; Spira et al., 2002). Este desenvolvimento tardio é visto como mais uma das características da TAA em reproduzir adequadamente o estado crônico da doença hepática (Masumi et al., 1999). Geralmente, são necessários anos de exposição ao agente tóxico para que grau semelhante de cirrose hepática se desenvolva no homem. "
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