Agents Affecting Lipid Metabolism: XXXVIII. Effect of Neomycin on Cholesterol Biosynthesis and Bile Acid Precipitation
AbstractMale albino rats were fed neomycin as 0.5% of the drinking water for 14 days. Liver homogenates and intestinal sections were prepared and incubated simultaneously with 2- 14 C-acetate and 3 H-mevalonate and the incorporation of these precursors into cholesterol was determined. Neomycin had no effect on the incorporation of precursors into hepatic cholesterol but caused almost a twofold increase in the incorporation of 14 C-acetate into intestine cholesterol. A similar dose of the bile acid sequestering agent, cholestyramine, caused more than a fourfold increase in both hepatic and intestinal cholesterol formation. Neomycin had no effect on serum and liver sterols, but caused a decrease in intestine sterol levels. Buffered (pH 6.4) solutions of neomycin were added to buffered solutions of sodium salts of various bile acids. Neomycin formed insoluble precipates with deoxycholate, taurodeoxycholate, and taurochenodeoxycholate, but did not precipitate cholate, taurocholate, or taurodehydrocholate. Thus, the antibiotic precipitated in vitro only dihydroxy bile acids. The results show that orally administered neomycin does not have a cholestyramine-like effect on the incorporation of labeled acetate and mevalonate into cholesterol and that this is due to the selective action of the antibiotic in precipitating bile acids. Inferences drawn from these data indicate that the hypocholesterolemic action of neomycin in man and the chick, however, may be mediated by precipitation of dihydroxy bile acid conjugates.