Dissolution of human cholesterol gallstones in stimulated chenodeoxycholate-rich and ursodeoxycholate-rich biles. An in vitro study of dissolution rates and mechanisms.
We have compared the kinetics and physical-chemical mechanisms of human cholesterol gallstone dissolution in simulated normal, chenodeoxycholate-rich, and ursodeoxycholate-rich " biles ." Owing to reduced micellar cholesterol solubilizing capacities, dissolution rates in ursodeoxycholate-rich biles were initially slower than in normal or chenodeoxycholate-rich biles . At later time points, dissolution rates in ursodeoxycholate-rich bile became accelerated; this was shown to be associated with the development of a lamellar liquid-crystalline phase that took place first on the stones' surfaces and was then followed by dispersion of liquid-crystalline vesicles into the micellar solution. As subsequent dissolution occurred in a two-phase system of micelles and liquid-crystalline vesicles, the quantity of cholesterol solubilized exceeded micellar saturation. In normal and chenodeoxycholate-rich biles , no phase changes were observed either on the surfaces of the stones or in the micellar solution, and the quantity of cholesterol solubilized was limited by micellar saturation. These results was limited by micellar saturation. These results are consistent with phase equilibria diagrams of the simulated bile systems and suggest that the predominant physical-chemical mechanism of in vivo gallstone dissolution with ursodeoxycholic acid is via liquid crystalline dispersion of cholesterol. In contrast, micellar dissolution of cholesterol is the only mechanism possible with chenodeoxycholic acid.
D001646:Bile / Q000378:metabolism*; D002635:Chenodeoxycholic Acid / Q000378:metabolism*; D002769:Cholelithiasis / Q000378:metabolism* / Q000473:pathology; D002784:Cholesterol; D003840:Deoxycholic Acid / Q000031:analogs & derivatives*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D014580:Ursodeoxycholic Acid / Q000378:metabolism*
D003840:Deoxycholic Acid; D002635:Chenodeoxycholic Acid; D014580:Ursodeoxycholic Acid; D002784:Cholesterol