Prairie dogs of both sexes were fed a semisynthetic diet containing 0.35%
cholesterol for a period of 8 weeks. This lithogenic diet induced
cholesterol gallstones in ten "lithogenic control animals", five males and five females. Three animals maintained with a high
glucose,
fat-free diet did not develop
gallstones although the
cholesterol saturation of their bile approached unity. The formation of
gallstones was prevented in four out of five males and all five females fed the lithogenic diet plus 0.1%
hyodeoxycholic acid (30 mg per kg
body weight per day). The biles of the prairie dogs receiving
hyodeoxycholic acid were abnormally colored, cloudy, and highly saturated with
cholesterol but contained neither
cholesterol crystals nor
gallstones (with the exception of one male). Feeding the relatively hydrophilic
bile acid,
hyodeoxycholic acid, was associated with an increase in hepatic microsomal
HMG-CoA reductase activity.
Cholesterol 7 alpha-hydroxylase, on the other hand, was inhibited by the administered
bile acid. The dietary
hyodeoxycholic acid was transformed, in part, to 3 alpha, 6 beta-dihydroxy-5-beta-cholanoic
acid and
hyocholic acid. It is concluded that
hyodeoxycholic acid and its metabolites did not prevent the induced
cholelithiasis by causing a decrease in the concentration of biliary
cholesterol. Instead, this hydrophilic
bile acid apparently increases the amount of
cholesterol in the bile, probably in the form of a liquid crystalline mesophase.
Hyodeoxycholic acid apparently prevents
gallstones by preventing the nucleation and aggregation of
cholesterol crystals. The lithogenic diet induced moderate to marked bile duct proliferation together with portal
fibrosis and inflammatory infiltration. The addition of
hyodeoxycholic acid to the lithogenic diet reduced all of the portal tract changes.