Effect of hyocholic acid on the prevention and dissolution of biliary cholesterol crystals in mice.
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.
Dusserre
J P
JP
INSERM Unité de recherches de pathologie digestive, Marseille, France.
Montet
A M
AM
Montet
J C
JC
D000818:Animals; D001646:Bile / Q000032:analysis / Q000187:drug effects*; D001647:Bile Acids and Salts / Q000032:analysis; D002779:Cholestasis / Q000517:prevention & control*; D002784:Cholesterol; D002793:Cholic Acids / Q000494:pharmacology*; D003460:Crystallization; D008055:Lipids / Q000032:analysis; D051379:Mice; D008823:Micelles
D001647:Bile Acids and Salts; D002793:Cholic Acids; D008055:Lipids; D008823:Micelles; C004821:muricholic acid; D002784:Cholesterol