Effect of 7-methylated bile acids and bile alcohols on cholesterol metabolism in hamsters

Abstract

The effect of 7-methyl substituted bile acid and bile alcohol analogues on cholesterol metabolism was studied in the hamster. Animals were fed chow plus 0.1% cholesterol supplemented with 0.1% of one of the following steroids: chenodeoxycholic acid, 7-methyl-chenodeoxycholic acid, 7 beta-methyl-24-nor-5 beta-cholestane-3 alpha, 7 alpha, 25-triol, cholic acid, 7-methyl-cholic acid, or 7 beta-methyl-24-nor-5 beta-cholestane-3 alpha, 7 alpha, 12 alpha,25-tetrol. Cholesterol absorption was determined from fecal analysis after feeding of radiolabeled cholesterol and beta-sitosterol. Of the six compounds studied, chenodeoxycholic acid and 7-methyl-chenodeoxycholic acid decreased intestinal cholesterol absorption (17% and 31% decrease, respectively). Only 7-methyl-chenodeoxycholic acid decreased serum cholesterol concentration (29% decrease), but there were no analogous changes of liver and biliary cholesterol concentration and cholesterol saturation of bile. Total fecal neutral sterol excretion was increased in the groups fed chenodeoxycholic acid and 7-methyl-chenodeoxycholic acid. In addition, the production of coprostanol was increased in both groups. These data suggest that 7-methyl-chenodeoxycholic acid resembles chenodeoxycholic acid in its effect on cholesterol metabolism and may be a potential candidate for further studies of its gallstone-dissolving properties.