Abstract
Cholestyramine, an anion exchange resin, is a hypolipidemic drug widely used as the bile acids sequestrant and Lipid Research Clinics Program reports showed its clinical benefit reducing the risk of coronary heart disease due to the decrease in total and LDL cholesterol in the serum (1984).
As MCI-196 a water insoluble anion exchange resin with an imidazolium base as a functional group on copolymer of epichlorohydrin and 2-methylimidazol, the hypolipidemic effects of MCI-196 were examined in both basal and 0.67% cholesterol diet fed rabbits (male New Zealand White strain) compared with cholestyramine. After cholesterol diet feeding for a week, the oral administrations of resins once a day were performed following 2 weeks at dosages of 125 and 500mg/kg, respectively.
The plasma cholesterol elevation by cholesterol diet feeding was markedly inhibited by MCI-196 treatment and statistical analysis showed MCI-196 was 4.3 fold more potent than cholestyramine. The plasma phospholipid levels elevated in cholesterol diet fed rabbits were also decreased by resin treatments, which was considered to be based on the reduction of VLDL and LDL lipids. The increases in the levels of liver cholesterol and the hepatic bile cholesterol and phospholipid by cholesterol diet feeding levels were also decreased by resin treatments, which revealed the reduction of the hepatic lipid pool. Their basal levels of plasma, liver and hepatic bile in basal diet fed rabbits were slightly decreased by resin treatments. No effects of resin on the levels of liver phospholipid and triglyceride, plasma triglyceride and biliary total bile acids were observed in both basal and cholesterol diet fed rabbits. On the other hand, the fecal sterol excretion (cholesterol and bile acids) were markedly increased by MCI-196 treatment in both basal and cholesterol diet fed rabbits. Cholestyramine stimulated fecal bile acid excretion but not cholesterol.
These results suggest that MCI-196 is a highly active bile acid sequestrant more than cholestyramine and inhibits the intestinal bile acid reabsorption and promotes cholesterol metabolism to bile acids and finally decreases plasma and liver cholesterol levels according to the same mechanism of cholestyramine.
