Stabilization of biliary lipid particles by ursodeoxycholic acid. Prolonged nucleation time in human gallbladder bile

We evaluated the effect of ursodeoxycholic acid on the metastability of human bile as reflected by nucleation time and also assessed the mechanism of its action in an ultrastructural study. Ursodeoxycholic acid significantly prolonged the nucleation time of gallbladder bile from cholesterol gallstone patients without causing either drastic changes in the distribution of cholesterol between the nonmicellar and micellar fractions of bile or biliary cholesterol desaturation. Gel permeation chromatography resolved two distinct components of the nonmicellar fraction: vesicles and phospholipid lamellae (identified by electron microscopy). Nonmicellar cholesterol was predominantly carried by vesicles in the bile of untreated gallstone patients, whereas it was chiefly carried by phospholipid lamellae in patients treated with ursodeoxycholic acid. Furthermore, phospholipid lamellae from untreated gallstone patients showed rapid transformation and cholesterol microcrystal formation within seven days, whereas the lamellae from ursodeoxycholic acid-treated patients were stabilized and showed little change. On the other hand, biliary mucin concentration was reduced by the treatment with ursodeoxycholic acid. These findings suggest that ursodeoxycholic acid stabilizes phospholipid lamellae and consequently prolongs nucleation time. It is also possible that the reduction of biliary mucin plays a role in this process.