Effect of some sulfonate analogues of ursodeoxycholic acid on biliary lipid secretion in the rat

• Published in: Journal of lipid research Vol. 37; no. 6; pp. 1181 - 1188
• Main Authors: Mikami, T, Kihira, K, Ikawa, S, Yoshii, M, Mosbach, E H, Hoshita, T
• Format: Journal Article
• Language: English
• Published: United States Elsevier 01.06.1996
• Subjects: Animals; Bile - drug effects; Bile - metabolism; Bile Acids and Salts - metabolism; Chenodeoxycholic Acid - analogs & derivatives; Chenodeoxycholic Acid - pharmacology; Cholesterol - metabolism; Fistula; Gallbladder - surgery; Kinetics; Male; Phospholipids - metabolism; Rats; Rats, Wistar; Ursodeoxycholic Acid - pharmacology
• ISSN: 0022-2275
• DOI: 10.1016/S0022-2275(20)39147-1

The effect of the sulfonate analogues of ursodeoxycholic acid, namely sodium 3 alpha,7 beta-dihydroxy-24-nor-5 beta-cholane-23-sulfonate (norUDC-SO3Na) and sodium 3 alpha, 7 beta-dihydroxy-5 beta-cholane-24-sulfonate (UDC-SO3Na), on biliary lipid secretion was studied in bile fistula rats. During intravenous infusion of the two sulfonate analogues, bile flow and biliary lipid secretion were stimulated in a dose-dependent manner. This suggests that the analogues exert an effect on biliary lipid secretion comparable to that of the naturally occurring bile acid, ursodeoxycholyltaurine (UDC-tau). The effects of norUDC-SO3Na and UDC-SO3Na on bile flow were similar but slightly smaller than that of UDC-tau. The output of bile salts was similar with both sulfonates but greater than that with UDC-tau. The infusion of norUDC-SO3Na or UDC-SO3Na induced cholesterol secretion and phospholipid secretion more significantly than UDC-tau infusion. The increase in phospholipid secretion was particularly pronounced during high-dose administration of norUDC-SO3Na. Although norUDC-SO3Na stimulated cholesterol secretion more intensely than the other two bile salts, it also facilitated phospholipid output, perhaps as a compensatory mechanism, and the biliary cholesterol/phospholipid ratio was decreased to a greater extent by the sulfonates than by UDC-tau. Consequently, the administration of norUDC-SO3Na or UDC-SO3Na produces a more "stable" bile than UDC-tau, suggesting that these sulfonates possess potential cholelitholytic activity.