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 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.
Masumi
S
S
Department of Veterinary Physiology, College of Agriculture, Osaka Prefecture University, Japan. masumisg@otsukakj.co.jp
Moriyama
M
M
Kannan
Y
Y
Ohta
M
M
Koshitani
O
O
Sawamoto
O
O
Sugano
T
T
D000410:Alanine Transaminase / Q000378:metabolism; D000641:Ammonia / Q000097:blood / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D004032:Diet; D005260:Female; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D005972:Glutaminase / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*; D009584:Nitrogen / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013853:Thioacetamide / Q000633:toxicity*; D013997:Time Factors; D014508:Urea / Q000378:metabolism / Q000652:urine
D013853:Thioacetamide; D005973:Glutamine; D000641:Ammonia; D014508:Urea; D005969:Glutamate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005972:Glutaminase; D005974:Glutamate-Ammonia Ligase; D009584:Nitrogen