Urea synthesis by perfused rat liver— Studies of CCI 4-induced cirrhosis

Abstract

Previous studies in man and experimental animals suggest that urea production is decreased in cirrhosis. In the present study, NH 4Cl solutions of increasing concentrations were infused into isolated, perfused livers of normal rats and the rates of ammonia uptake and urea production were calculated for each pre-hepatic ammonia concentration. A pattern of saturation kinetics was generated and characterized through computer analysis. The V max was 7.4 μmoles/min and K m was 86.3 μmoles/100 ml. The livers of rats with experimental cirrhosis induced by carbon tetrachloride produced less urea than controls (controls : 0.40 ± 0.03 ; cirrhotic 0.25 ± 0.02 μmole/min/g of wet liver weight ; P < 0.005) at infusion rates of NH 4Cl, which resulted in ammonia levels approximately twice the K m value. Simultaneously performed taurocholate transport studies also revealed significant functional differences between cirrhotic and control livers. In summary, this study delineates a model to evaluate the kinetics of urea synthesis from NH 4Cl in the isolated perfused rat liver. It was found that the livers of rats with CCl 4-induced cirrhosis exhibited impaired ammonia utilization and urea production together with abnormalities of taurocholate transport.