Microsomal drug metabolism in acute and chronic galactosamine induced hepatic injuries.

Abstract

To determine the microsomal functions of the injured liver, female rats were given D-galactosamine (GalN) acutely (400 mg/kg body weight, i.p.) or chronically (250 mg/kg body weight for 7 months, daily, i.p.). In the acute study, GalN administration resulted in a five-fold increase in hepatic triglyceride content. Microsomal protein and phospholipid concentrations were not affected. However microsomal cytochrome P450 content and aminopyrine demethylase and also aniline hydroxylase activities were significantly decreased whether expressed per mg of microsomal protein or per gram of liver. Cytochrome b5 content was significantly increased. By contrast, chronic administration of GalN produced a marked hepatomegaly and an extensive hepatic fibrosis with nodular formation without triglyceride accumulation. Electron-microscopically, there was apparent proliferation of mitochondria, and smooth endoplasmic reticulum showed focally accentuated hypertrophy without liposomes in the dilated tubules. Although microsomal protein concentration was significantly decreased, cytochrome P450 content was increased significantly when expressed per mg of microsomal protein or per unit of body weight. The aminopyrine demethylase activity was significantly enhanced only when expressed per unit of body weight. In both acute and chronic studies, microsomal glucose-6-phosphatase activity was significantly reduced. These data suggest that in acute liver injury, there is an impairment of hepatic microsomal drug metabolizing activity, whereas in chronic liver injury, there is an apparent enhancement of the activity possibly due to an enlarged hepatic mass even in the presence of a decreased drug metabolizing capacity per unit of the injured liver.