MECHANISMS OF THE HYPOLIPIDEMIC EFFECT OF NIP-200 IN RATS

We studied the mechanisms of hypolipidemic effects of NIP-200 iphenyl- tetrahydro-2H-1,3,5-thiadiazine-2-thione), a potent hypolipidemic comp ound, in cholesterol biosynthesis in the liver, cholesterol absorption in small intestine, and cholesterol catabolism and excretion in rats. NIP-200 did not reduce cholesterol biosynthesis and had no effects on cholesterol absorption in the small intestine. In the cholesterol cat abolism and excretion, NIP-200 induced increases in cholesterol and bi le acids levels in the bile and acidic steroids in the feces, and it e nhanced cholesterol 7alpha-hydroxylase activity in the liver. These re sults suggest that NIP-200 increases the synthesis of bile acids as a result of the activation of cholesterol 7alpha-hydroxylase, the rate-l imiting enzyme in the conversion of cholesterol to bile acids. Therefo re, it is considered that one of the probable mechanisms of the serum total cholesterol lowering action of NIP-200 involves the enhancement of catabolism and excretion of cholesterol in the liver.