Effect of Zanchol and Chenic Acid on Bile Acid Pool Size and Gallstones in Hamsters

Abstract

After receiving a lithogenic regime for 12weeks (Phase I), 60 hamsters were allocated to groups of 10 animals. During Phase II, except for one group which remained on the lithogenic regime, all groups were switched to a standard diet and chenic acid 20mg/kg/day or Zanchol 5, 15 or 25mg/kg/day or no other therapy. Half the animals in each group were sacrificed at 3weeks and the remainder at 10weeks. Gallstones were found in all animals except those receiving chenic acid for 10weeks. At 3weeks in Phase II, with chenic acid, the bile acid pool size was not significantly decreased and bile remained saturated despite a 38% lower rate of hepatic synthesis of cholesterol (p<0.01), but became unsaturated at 10weeks at which time the bile acid pool size was increased by 37% (p<0.01). The highest dose of Zanchol increased the bile acid pool size by 74% (p<0.01) while increasing the hepatic synthesis of bile acids by 38% (p<0.01). None of the doses of Zanchol, however, significantly changed biliary cholesterol saturation.In conclusion, chenic acid decreased the hepatic synthesis of cholesterol prior to increasing the bile acid pool, unsaturating bile and dissolving gallstones. Zanchol did not affect the biliary cholesterol saturation or dissolve gallstones despite an increase in the synthesis and pool size of the bile acids.