Abstract
The gallbladder role in cholesterol gallstone pathogenesis occurs through modulation of bile cholesterol metastability. The present study characterized the effects of concentrating bile on cholesterol crystallization through vesicle transformation, crystal habits, and potentiation of effector substances. Supersaturated model biles with total lipid concentrations of 12, 9, 6, and 3 g/dl were prepared with identical molar ratios (taurocholate–egg yolk phosphatidylcholine–cholesterol: 71:18:11). Bile metastability was assessed spectrophotometrically, and morphology of vesicle and crystal was sequentially scanned by video-enhanced differential contrast microscopy. The effects of replacing 30% of egg yolk phosphatidylcholine with soy bean phosphatidylcholine, 30% of taurocholate with taurodeoxycholate or tauroursodeoxycholate, and addition of concanavalin A-binding glycoprotein on each model bile were examined. By lowering total lipid concentration, cholesterol crystallization was retarded with less fusion and aggregation of vesicles. The effects of substances promoting cholesterol crystallization were enhanced with lesser bile. By replacing 30% of taurocholate with tauroursodeoxycholate, cholesterol crystallization was markedly inhibited in all concentrations, forming stable liquid-crystals. Impaired water absorption by the gallbladder may stabilize vesicles and inhibit rapid cholesterol crystallization, but the potential of cholesterol crystallization effector substances must be modified to alter bile cholesterol metastability.
Similar content being viewed by others
REFERENCES
Holzbach RT: Nucleation of cholesterol crystals in native bile. Hepatology 12:155S-161S, 1990
Halpern Z, Dudley MA, Lynn MP, Nader JM, Breuer AC, Holzbach RT: Vesicle aggregation in model systems of supersaturated bile: Relation to crystal nucleation and lipid composition of the vesicular phase. J Lipid Res 27:295-306, 1986
Afdhal NH, Nui N, Nunes DP, Banisil R, Gao XX, Gantz D, Small DM, Offner GD: Mucin-vesicle interactions in model bile: Evidence for vesicle aggregation and fusion before cholesterol crystal formation. Hepatology 22:856-865, 1995
Halpern Z, Dudley MA, Kibe A, Lynn MP, Breuer AC, Holzbach RT: Rapid vesicle formation and aggregation in abnormal human biles. A time-lapse video-enhanced contrast microscopy study. Gastroenterology 90:875-885, 1986
Carey MC: Critical tables for calculating the cholesterol saturation of native bile. J Lipid Res 19:945-957, 1978
Kibe A, Holzbach RT, LaRusso NF, Mao SJT: Inhibition of cholesterol crystal formation by apolipoproteins in supersaturated model bile. Science 225:514-516, 1984
Groen AK, Noordam C, Drapers JAG, Egbers P, Jansen PLM, Tygat GNT: Isolation of a potent cholesterol nucleationpromoting activity from human gallbladder bile. Hepatology 11:525-533, 1990
Teramen K, Tazuma S, Ohya T, Kajiyama G: Comparative effects on biliary concanavalin A-bound glycoproteins and calcium ion on cholesterol crystallization. J Gastroenterol Hepatol 11:738-745, 1996
Yamashita G, Ginanni CS, Secknus R, Takabayashi A, Williams C, Hays L, Chernosky AL, Holzbach RT: Biliary Haptoglobin, a potent promoter of cholesterol crystallization at physiological concentrations. J Lipid Res 36:1325-1333, 1995
Nishioka T, Tazuma S, Yamasita G, Kajiyama G: Quantitative assessment of comparative potencies of cholesterol-crystalpromoting factor: Relation to mechanistic characterization. Biochem J 332:343-350, 1998
Tazuma S, Ochi H, Teramen K, Yamashita Y, Horikawa K, Miura H, Hirano N, Sasaki M, Aihara N, Hatsushika S: Degree of fatty acyl chain unsaturation in biliary lecithin dictates cholesterol nucleation and crystal growth. Biochim Biophys Acta 17:74-78, 1994
Holzbach RT: Current concepts of cholesterol transport and crystal formation in human bile. Hepatology 12:26S-32S, 1990
Juste C, Catala I, Henry R, Chabanet C, Gueugneau AM, Beguet F, Lyan B, Corring T: Influence of bile salt molecular species on cholesterol crystallization from supersaturated model biles. Biochim Biophys Acta 1254:89-97, 1995
Jüngst D, Lang T, Huber P, Lange V, Paugartner G: Effect of phospholipid and bile acids on cholesterol nucleation time and vesicular/micellar cholesterol in gallbladder bile of patients with cholesterol stones. J Lipid Res 34:1457-1464, 1993
Konikoff FM, Cohen DE, Carey MC: Phospholipid molecular species influence crystal habits and transition sequences of metastable intermediates during cholesterol crystallization. J Lipid Res 35:60-70, 1994
Van de Heijning BJM, Stolk MFJ, Van Erpecum KJ, Renooiji W, Groen AK, Van Berge Hengouwen GP: Bile salt-induced cholesterol crystal formation from model bile vesicles: a time course study. J Lipid Res 35:1002-1011, 1994
Ochi H, Tazuma S, Kajiyama G: Lecithin hydrophobicity modulates the process of cholesterol crystal nucleation and growth in supersaturated model bile systems. Biochem J 318:139-144, 1996
Van Erpecum KJ, Portinacasa P, Stolk MFJ, Van de Heijning BJM, Van der Zaag ES, Van den Broek AMWC, Van Berge Hengouwen GP, Renooij W: Effects of bile salt and phospholipid hydrophobicity on lithogenecity of human gallbladder bile. Eur J Clin Invest 24:744-750, 1994
Hussaini SH, Pereira SP, Murphy GM, Dowling RH: Deoxycholic acid influences cholesterol solubilization and microcrystal nucleation time in gallbladder bile. Hepatology 22:1735-1744, 1995
Nishioka T, Tazuma S, Kajiyama G: Partial replacement of bile salts causes marked changes of cholesterol crystallization in supersaturated model bile systems. Biochem J 340:445-451, 1999
Kibe A, Dudley MA, Halpern Z, Lynn MP, Breuer AC, Holzbach RT: Factors affecting cholesterol monohydrate crystal nucleation time in model systems of supersaturated bile. J Lipid Res 26:1102-1111, 1985
Van Erpecum KJ, Van Berge Hengouwen GP, Stoelwinder B, Schmidt YMG, Willekens FLH: Bile concentration is a key factor for nucleation of cholesterol crystals and cholesterol saturation index in gallbladder bile of gallstone patients. Hepatology 11:1-6, 1990
Van Erpecum KJ, Stolk MFJ, Van den Broek AMWC, Renooij W, Van de Heijning BJM, Van Berge Hengouwen GP: Bile concentration promotes nucleation of cholesterol monohydrate crystals by increasing the cholesterol concentration in the vesicles. Eur J Clin Invest 23:283-288, 1993
Laemmli UK: Clavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680-685, 1970
Donovan JM, Jackson AA: Rapid determination by centrifugal ultrafiltration of inter-mixed micellar/vesicullar (nonlecithin associated) bile salt concentrations in model bile; Influence of Donnan equilibrium effects. J Lipid Res 34:1121-1129, 1993
Holan KR, Holzbach RT, Hermann RE, Cooperman AM, Claffey WJ: Nucleation time: A key factor in the pathogenesis of cholesterol gallstone disease. Gastroenterology 77:611-617, 1979
Yamashita Y, Tazuma S, Kajiyama G: Method for quantitative assessment of transformation of non-micellar cholesterol carriers in model bile system. J Gastroenterol Hepatol 11:864-869, 1996
Donovan JM, Jackson AA: Accurate separation of biliary lipid aggregates requires the correct intermixed micellar/intervesicular bile salt concentration. Hepatology 27:641-648, 1998
Eckhadt ERM, Van de Heijning BJM, Van Erpecum KJ, Renooiji W, Van Berge Hengouwen GP: Quantitation of cholesterol-carrying particles in human gallbladder bile. J Lipid Res 39:594-603, 1998
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Sunami, Y., Tazuma, S. & Kajiyama, G. Gallbladder Dysfunction Enhances Physical Density But Not Biochemical Metastability of Biliary Vesicles. Dig Dis Sci 45, 2382–2391 (2000). https://doi.org/10.1023/A:1005695109908
Issue Date:
DOI: https://doi.org/10.1023/A:1005695109908