AMELIORATION OF DISORDERED HEPATIC PROTEIN-SYNTHESIS BY THE DELETED FORM OF HEPATOCYTE GROWTH-FACTOR IN MODELS OF LIVER-FAILURE IN RATS

Because the liver plays an important role in protein synthesis and cho lesterol metabolism and reductions in these functions are observed in almost all hepatic disorders, the effects of the deleted form of hepat ocyte growth factor (dHGF) on disordered hepatic protein synthesis wer e studied in various liver-injured rat models using Wistar male rats. In the 70% hepatectomized rats, plasma clotting time was prolonged and the serum level of total protein and the liver protein content were d ecreased. The treatment of the animals with dHGF (100-500 mu g kg(-1), i.v., twice daily) ameliorated these parameters at 48 or 72 h. The ad ministration of carbon tetrachloride or D-galactosamine to hepatectomi zed rats induced a marked prolongation of plasma clotting time and hyp oproteinaemia. In the animals treated with dHGF (500 mu g kg(-1), i.v. , twice daily) these parameters were rapidly reversed compared with th ose of control groups. In a hepatocellular necrosis model induced by d imethylnitrosamine, the plasma clotting time was extremely prolonged, and liver protein content, serum total protein, albumin, HDL-cholester ol (as an index of lipoprotein) and plasma lecithin-cholesterol acyltr ansferase activity severely reduced. In this severely injured model, d HGF (5-500 mu g kg(-1), i.v., twice daily for 28 days) dose-dependentl y prevented the loss of liver protein content and improved the disorde red plasma coagulability and serum protein levels. These results sugge st that dHGF is useful for ameliorating the disorders in hepatic funct ions such as protein synthesis.