Action of malotilate on reduced serum cholesterol level in rats with carbon tetrachloride-induced liver damage

The mode of action of malotilate in normalizing serum Cholesterol in hypocholesterolemic rats with fatty liver was examined by determination of biosynthesis, catabolism and excretion of Cholesterol. Fatty liver was produced by subcutaneous injection of CCl4 at the dose of 1 ml/kg into male rats (SLC-SD) twice a week for 3 weeks. Daily administration of malotilate (100 mg/kg) in rats with hypocholesterolemia resulted in a rapid normalization of lowered serum Cholesterol. Such a recovery of Cholesterol level in serum coincided in time with normalization of the decreased Cholesterol level of each lipoprotein fraction, VLDL-triglycerides secretion and the decreased apolipoprotein A1 value. Histopathological improvement in liver was also confirmed by a decrease in the size of fat droplets stored within the hepatocytes. The malotilate treatment gave a tendency to facilitate hepatic Cholesterol synthesis in rats with fatty liver. Malotilate at a concentration of 0.5-2 micrograms/ml also stimulated Cholesterol biosynthesis in cultured normal hepatocytes. The drug had the action to accelerate the catabolic excretion of 3H-labeled Cholesterol into feces. These results suggest that the mode of action by which serum Cholesterol is normalized in rats with fatty liver is probably due to a stimulative effect of malotilate on hepatic Cholesterol synthesis and Cholesterol secretion from the liver.