We studied the effects of putrescine on acute liver failure caused in rats by two injections of 1 gmkg D-galactosamine. The hepatic polyamine level rose only slightly in the D-galactosamh&njected rats treated with glucagon and insulin, and ['Hlthymidine incorporation into DNA increased little; these hormones did not improve the survival rate. When D-galactosamineinjected rats were given putrescine, the putrescine concentration in the liver increased and the survival rate of the rats was significantly higher than that of control rats given only D-gdactosamine. Putrescine administration tended to lower the serum level of alanine amhotransferase in rats injected with Dgalactosamine, so the polyamine might have a protective effect on hepatocytes. Putrescine significantly increased ['Hlthymidine incorporation in the liver; thus it accelerated liver regeneration. Difluoromethylornithine decreased the level of putrescine in the liver, decreasing both ['Hlthymidine uptake and the survival rate. In the rats treated with D-gdactosamine, in which liver damage was so severe that treatment with glucagon and insulin was ineffective, the intraperitoneal administration of putrescine increased the survival rate in acute liver failure. This probably resulted mainly from activation of liver regeneration and possibly from a protective effect of putrescine on the liver. (HEPATOLOGY 1990; 12:348-353.)
Fulminant hepatitis, which can be caused by viral infection and drugs, is a serious disease with a survival rate of less than 40% (1). The most appropriate treatment is to help prevent the progressive necrosis of hepatocytes and to encourage liver regeneration. In experimental animals, administration of glucagon and insulin (GI) improves both the survival rate and DNA synthesis in fulminant hepatic failure caused by murine hepatitis virus or dimethylnitrosamine (2, 3). Baker et al. (4) found that GI infusion tended to improve the mortality rate in patients with alcoholic hepatitis. Okita