Effects of hydrophobic and hydrophilic bile salt mixtures on cholesterol crystallization in model biles.
The hydrophilic bile salt ursodeoxycholate is frequently used to dissolve cholesterol gallstones. We have now quantitated crystallization as a function of bile salt hydrophobicity, phospholipid content, cholesterol saturation and total lipid concentration (TLCo).


METHODS
Crystallization in supersaturated model biles with low phospholipid contents (left two-phase-micelles and crystal-containing-zone) was assessed during 21 days by microscopy and chemical measurement of crystal mass. For model biles with higher phospholipid contents (central three-phase-micelles, vesicles and crystal-containing-zone), lipid distribution into various phases was determined by combined ultracentrifugation-filtration-dialysis methodology (Biochim. Biophys. Acta 1532 (2001) 15-27).


RESULTS
In the left two-phase zone, crystal numbers and masses were highest in case of more hydrophilic bile salt composition (TUDC 100%>TC/TUDC 70%/30%>TC 100%>TC/TDC 70%/30%>TDC 100%) and decreased with increasing phospholipid contents, lower TLCo and lower cholesterol saturation index (CSI). In contrast, in the presence of vesicles (three-phase zone), crystallization decreased at increasing bile salt hydrophilicity, with concomitant increased vesicular cholesterol solubilization.


CONCLUSIONS
Presence of vesicular phases is a prerequisite for inhibition of cholesterol crystallization by tauroursodeoxycholate.
Venneman
Niels G
NG
Gastrointestinal Research Unit, Department of Gastroenterology, University Medical Center Utrecht, Utrecht, The Netherlands.
Huisman
Sebastiaan J
SJ
Moschetta
Antonio
A
vanBerge-Henegouwen
Gerard P
GP
van Erpecum
Karel J
KJ
D001647:Bile Acids and Salts / Q000737:chemistry*; D002769:Cholelithiasis / Q000209:etiology*; D002784:Cholesterol / Q000737:chemistry*; D003460:Crystallization; D057927:Hydrophobic and Hydrophilic Interactions; D008823:Micelles; D010713:Phosphatidylcholines / Q000737:chemistry; D013655:Taurochenodeoxycholic Acid / Q000737:chemistry; D013656:Taurocholic Acid / Q000737:chemistry; D013657:Taurodeoxycholic Acid / Q000737:chemistry
D001647:Bile Acids and Salts; D008823:Micelles; D010713:Phosphatidylcholines; D013655:Taurochenodeoxycholic Acid; D013657:Taurodeoxycholic Acid; D013656:Taurocholic Acid; C031655:ursodoxicoltaurine; D002784:Cholesterol