Bile Acid Sulfonates Alter Cholesterol Gallstone Incidence in Hamsters

The prevention of cholesterol gallstone formation by three bile acid analogs, sodium 3α,7α‐dihydroxy‐5β‐cholane‐24‐sulfonate, sodium 3α,7β‐dihydroxy‐5β‐cholane‐24‐sulfonate and sodium 3α, 6α‐dihydroxy‐5β‐cholane‐24‐sulfonate, was examined in a hamster model of cholesterol cholelithiasis. Sodium taurochenodeoxycholate, sodium tauroursodeoxycholate and sodium taurohyodeoxycholate were studied simultaneously for comparison. Gallstones and cholesterol crystals were induced in 14 of 15 hamsters fed a bile acid–free, semipurified lithogenic diet containing 0.3% cholesterol and 4% butterfat for 6 wk. The addition of 0.1% sodium taurochenodeoxycholate and sodium tauroursodeoxycholate to the lithogenic diet had little effect on the formation of gallstones or biliary cholesterol crystals. In contrast, sodium 3α,7β‐dihydroxy‐5β‐cholane‐24‐sulfonate and sodium 3α,7β‐dihydroxy‐5β‐cholane‐24‐sulfonate, when fed at the same dose, prevented cholesterol gallstone formation significantly. Sodium taurohyodeoxycholate and sodium 3α,6α‐dihydroxy‐5β‐cholane‐24‐sulfonate inhibited cholesterol gallstone formation effectively. The cholesterol saturation index of bile was greater than 1.00 in all groups, with the exception of the group fed sodium 3α,7α‐dihydroxy‐5β‐cholane‐24‐sulfonate. Liver and serum cholesterol levels tended to be lower in most of the groups that were fed bile acids. This effect was most pronounced in the animals receiving sodium taurohyodeoxycholate. At the end of the experiment, the administered sulfonate analogs were detected in gallbladder bile. Sodium 3α,7α‐dihydroxy‐5β‐cholane‐24‐sulfonate (32.7%) became the major biliary bile acid; smaller percentages of the administered bile acid sulfonates were recovered in the bile of the groups fed sodium 3α,7β‐dihydroxy‐5β‐cholane‐24‐sulfonate (12.3%) and sodium 3α, 6α‐dihydroxy‐5β‐cholane‐24‐sulfonate (17.4%). The bile of the hamsters that were fed sodium taurochenodeoxycholate and sodium taurohyodeoxycholate contained considerable amounts of chenodeoxycholic acid (50.6%) and hyodeoxycholic acid (40.0%), respectively. On the other hand, in the bile of the group that was fed sodium tauroursodeoxycholate, ursodeoxycholic acid accounted for less than 1% of the total bile acids; the bile acid composition was similar to that of the group that was fed sodium taurochenodeoxycholate. We concluded that the sulfonate analogs of three dihydroxy bile acids suppressed the formation of cholesterol gallstones in a hamster model of cholesterol cholelithiasis. Their efficacy increased in the following order: sodium 3α,7α‐dihydroxy‐5β‐cholane‐24‐sulfonate, sodium 3α, 6α‐dihydroxy‐5β‐cholane‐24‐sulfonate, sodium 3α,7β‐dihydroxy‐5β‐cholane‐24‐sulfonate; however, it was not directly related to their concentration in bile at the end of the feeding period (6 wk). (HEPATOLOGY 1993;17:103–110.)