[Role of sodium ion on the cholesterol solubilization in bile in relation to cholesterol gallstone formation (author's transl)].
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Biomedical subjects
Publications and source records attributed to T Hisadome.
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It is now relatively well established that chenodexoycholic acid (CDCA) and ursodeoxycholic acid (UDCA), which are 7-OH epimer, are cholesterol gallstone dissolving agent. We investigated physical-chemical properties of CDCA and UDCA with respect to critical micellar concentration (CMC), micellar molecular weights (MMW) and solubilizing power of cholesterol. CMCs of CDCA and UDCA, measured by surface tension method, were 3.6 mM and 6.4 mM respectively. Light scattering technique revealed the MMW as 7700 in CDCA and 7400 in UDCA of only one molecule's difference per micelle in the aggregation number. Solubilization of cholesterol in model bile system disclosed remarkable difference. The degree of solubilized cholesterol by UDCA was smaller than that of CDCA by a factor of about 19. Addition of lecithin produced a greater increment of solubilized cholesterol in UDCA, but the solubilizing power was still larger in CDCA. It is curious and of interest that there exists much difference in the aspects of solubilizing efficiency for cholesterol in the in vitro model system, inspite of their little difference in the molecular structure, CMC and MMW between CDCA and UDCA. 7 beta-OH might affect the function of micelle against solubilization in UDCA.
Not only cholesterol but also bilirubin were considered to be solubilized by bile salt micelles. The correlation of cholesterol and bilirubin solubilization in aqueous conjugated and unconjugated bile salts solution and the effect of calcium on their solubilization were studied in this report. Cholesterol solubilization was usually reduced to some extent with increasing amount of added bilirubin. Bilirubin solubilization was always reduced by the co-existence of solubilized cholesterol. It was found that the addition of calcium increased cholesterol solubilization in conjugated bile salts system. On the other hand, calcium reduced bilirubin solubilization due to the formation of insoluble calcium bilirubinate especially in a high pH range of unconjugated bile salts system. Cholesterol solubilization in conjugated bile salts system was relatively lower than unconjugated bile salts system with or without added calcium, however co-existing bilirubin minimized these differences. The pH-dependency of cholesterol and bilirubin solubilization was small in conjugated bile salts system. On the contrary, it was remarkably bigger in unconjugated bile salts-calcium system.
On the basis obtained in a preceding study, cholesterol solubilization in aqueous bile salt-lecithin solution was investigated. The alteration of mixing sequence was found to yield differences not only in the rate but also in the magnitude of cholesterol solubilization. Both the rate and the magnitude were remarkably bigger in the system solubilizing cholesterol and lecithin mixture by bile salt than that solubilizing cholesterol crystal by bile salt with solubilized lecithin. A linear relation between the quantity of solubilized cholesterol and the concentration of bile salt except for lower concentration range was obtained for every bile salt-lecithin system. Values of k, the slope of the partial straight line, determined for cholate, chenodeoxycholate, deoxycholate and equimolar cholate-deoxycholate systems were 5.85 X 10(-2), 7.60 X 10(-2), 9.50 X 10(-2) and 7.17 X 10(-2), respectively. Cholesterol solubilizing power of bile salt was thus enhanced by the addition of lecithin. Since the solubilizing power could be given by the ratio of the solubilizate to the solubilizer, it was expressed graphically by the ratio of cholesterol to bile salt as ordinate and the concentration of bile salt as abscissa. The saturability of cholesterol solubilization in bile was purposefully exhibited in this graph by plotting assayed data of biliary lipid components.
Previous studies on cholesterol solubilization by bile salts have often shown inconsistencies. To obtain basic informations on this problem, cholesterol solubilization in the aqueous solution of several bile salts have been reexamined. Kinetic studies revealed that not only the rate but also the magnitude of solubilization depended on the amount of excess cholesterol and the concentration of bile salt. An appropriate proportion of added cholesterol to bile salt was evaluated as 1:5-10 (w/w), corresponding to about 200% excess amount to approximate supposed solubility. The solubilization equilibrium was rather difficult to fix and must be checked by the procedure used. A linear relation was obtained between the quantity of solubilized cholesterol and the concentration of bile salt. The slope of the straight line was designated k. As the solubilizing power could be given by the ratio of the solubilizate to the solubilizer, it was expressed numerically by k value as well as graphically by the molar ratio of cholesterol to bile salt as ordinate and the molar concentration of bile salt as abscissa in which the above relation was hyperbolic, k being as asymptote. k values obtained for cholate, chenodeoxycholate, deoxycholate and equimolar cholate-deoxycholate mixture were 3.72 X 10(-2), 6.79 X 10(-2), 8.10 X 10(-2) and 6.55 X 10(-2) respectively.