Gallstone prevention and dissolution were studied in a mouse model of
cholesterol cholelithiasis using
hyocholic acid (3 alpha, 6 alpha, 7 alpha-trihydroxy-5 beta-
cholanic acid). Addition of
hyocholic acid, 0.1 or 0.3%, in the lithogenic diet (1%
cholesterol + 0.5%
cholic acid) prevented the formation of
cholesterol monohydrate crystals in 70 and 90% of cases, respectively. On the other hand, chow diet supplemented with 0.1 or 0.3%
hyocholic acid dissolved
cholesterol crystals in lithiasic mice in, respectively, 80 and 100% of cases within 12 days. In both protocols, biles were largely supersaturated with
cholesterol;
lecithin-
cholesterol lamellar liquid crystals were responsible for the transport of the excess
cholesterol content. The percentage of hydrophilic
bile salts (
hyocholic acid,
hyodeoxycholic acid,
beta-muricholic acid) in bile, although moderate (15-50% of total
bile salts), appears to induce such liquid crystalline dispersion. This study demonstrates that the balance between hydrophilic and hydrophobic
bile salts plays a major role in the prevention and dissolution of
cholesterol crystals. It is also shown that the desaturation of biliary
cholesterol is not a prerequisite for
gallstone dissolution.