The purpose of this study was to compare the effects of the naturally occurring
bile acids (
chenodeoxycholic acid and
cholic acid) with their 7-methyl analogues (3 alpha,7 alpha-dihydroxy-7 beta-methyl-5 beta-
cholanoic acid and 3 alpha,7 alpha,12 alpha-trihydroxy-7 beta-methyl-5 beta-
cholanoic acid) on
gallstone formation and prevention and
cholesterol metabolism in the prairie dog. Sixty animals were fed a semipurified diet, containing 0.4%
cholesterol, with one of the following
acids (0.1%): chenodeoxycholic, cholic, 3 alpha,7 alpha-dihydroxy-7 beta-methyl-5 beta-cholanoic, or 3 alpha,7 alpha,12 alpha-trihydroxy-7 beta-methyl-5 beta-
cholanoic acid. This concentration of dietary
bile acids amounts to a dose of 27-30 mg/kg.day. After 8 wk, 89% of control animals had
gallstones and 94% had
cholesterol crystals. Chenodeoxycholic and 3 alpha,7 alpha-dihydroxy-7 beta-methyl-5 beta-cholanoic
acids decreased the incidence of
gallstones to 50%.
Cholic acid and 3 alpha,7 alpha,12 alpha-tri-hydroxy-7 beta-methyl-5 beta-
cholanoic acid did not prevent
gallstone formation. The liver
cholesterol level was decreased by
chenodeoxycholic acid, whereas cholic and 3 alpha,7 alpha,12 alpha-trihydroxy-7 beta-methyl-5 beta-cholanoic
acids increased serum and liver
cholesterol. Each administered
bile acid became the predominant biliary
bile acid and 7-methyl analogues did not increase secondary
bile acids. Fecal analysis of radioactive metabolites using 14C-labeled 7-methyl analogues showed that these compounds are resistant to bacterial 7-dehydroxylation. It was concluded that
3 alpha,7 alpha-dihydroxy-7 beta-methyl-5 beta-cholanoic acid inhibited
gallstone formation as effectively as
chenodeoxycholic acid, whereas both cholic and 3 alpha,7 alpha,12 alpha-trihydroxy-7 beta-methyl-5 beta-cholanoic
acids were not effective. The effects of 7-methyl analogues on the parameters of
cholesterol metabolism that we studied were similar to those of their parent compounds, chenodeoxycholic and
cholic acids. Thus,
3 alpha,7 alpha-dihydroxy-7 beta-methyl-5 beta-cholanoic acid but not 3 alpha,7 alpha,12 alpha-trihydroxy-7 beta-methyl-5 beta-
cholanoic acid offers promise in cholelitholytic
therapy for the prevention and possibly dissolution of
cholesterol gallstones.