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 cholesterol metabolism and reductions in these functions are observed in almost all hepatic disorders, the effects of the deleted form of hepatocyte growth factor (dHGF) on disordered hepatic protein synthesis were 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 decreased. The treatment of the animals with dHGF (100-500 micrograms kg-1, i.v., twice daily) ameliorated these parameters at 48 or 72 h. The administration of carbon tetrachloride or D-galactosamine to hepatectomized rats induced a marked prolongation of plasma clotting time and hypoproteinaemia. In the animals treated with dHGF (500 micrograms kg-1, i.v., twice daily) these parameters were rapidly reversed compared with those of control groups. In a hepatocellular necrosis model induced by dimethylnitrosamine, the plasma clotting time was extremely prolonged, and liver protein content, serum total protein, albumin, HDL-cholesterol (as an index of lipoprotein) and plasma lecithin-cholesterol acyltransferase activity severely reduced. In this severely injured model, dHGF (5-500 micrograms kg-1, i.v., twice daily for 28 days) dose-dependently prevented the loss of liver protein content and improved the disordered plasma coagulability and serum protein levels. These results suggest that dHGF is useful for ameliorating the disorders in hepatic functions such as protein synthesis.
Masunaga
H
H
Life Science Research Institute, Snow Brand Milk Products Co. Ltd, Tochigi, Japan.
Fujise
N
N
Shiota
A
A
Yamashita
Y
Y
Yasuda
H
H
Higashio
K
K
D000818:Animals; D008076:Cholesterol, HDL / Q000097:blood; D004128:Dimethylnitrosamine; D006498:Hepatectomy; D017228:Hepatocyte Growth Factor / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D017093:Liver Failure / Q000188:drug therapy*; D008297:Male; D014176:Protein Biosynthesis; D011517:Prothrombin Time; D051381:Rats; D017208:Rats, Wistar
D008076:Cholesterol, HDL; D017228:Hepatocyte Growth Factor; D004128:Dimethylnitrosamine