THE HYPOCHOLESTEROLEMIC ACTION OF TA-7552 AND ITS EFFECTS ON CHOLESTEROL-METABOLISM IN THE RAT

The hypocholesterolemic property of oxycarbonyl)-4-hydroxy-6,7,8-trime thoxynaphthalene (TA-7552) and its effects on cholesterol metabolism w ere investigated in the rat. TA-7552 incorporated into a hypercholeste rolemic diet at a concentration of 0.2% and administered for 7 days re duced serum cholesterol by 72% and liver cholesterol by 90%, and its m inimal effective dose was 0.01% in the diet. Its hypocholesterolemic e ffect was associated with an elevation of serum HDL-cholesterol, Inclu sion of 0.1% TA-7552 in the normal laboratory chow accelerated fecal e xcretion of C-14 derived from orally administered 4-[C-14]cholesterol or carbonyl-[C-14]taurocholate. The net amounts of fecal neutral stero ls and bile acids were markedly increased by the same treatment. Hepat ic bile acid production and hepatic and intestinal cholesterol biosynt hesis as measured by cholesterol 7 alpha-hydroxylase activity and 1-[C -14]acetate incorporation into tissue cholesterol, respectively, were both stimulated by the drug treatment. All these data indicate that th is hypocholesterolemic agent inhibits intestinal absorption of both ch olesterol and bile acids and compensatorily stimulates hepatic product ion of bile acids and cholesterol.