Animal Models of Calcium Cholelithiasis

Abstract

Bile contains four calcium anions which are readily precipitated by calcium: bilirubinate, “palmitate”, carbonate and phosphate. Precipitation of insoluble calcium salts is common in calculous biliary disease. All animal models of calcium cholelithiasis probably share a common pathogenesis-an increased concentration of a calcium-sensitive anion. In calcium bilirubinate cholelithiasis, an increased concentration of bilirubinate occurs. In mice, this occurs in animals having a genetic hemolytic anemia; in rats, it may be induced by an essential fatty acid in combination with diet modification; in dogs, by a low-taurine, low-protein diet; and in prairie dogs, by ileal resection which probably increases the bilirubinate/bile acid ratio in bile. In the two models of calcium-bile acid cholelithiasis, an increased biliary concentration of a calcium-sensitive glycine conjugated bile acid is induced by administration of a suitable precursor. In the rabbit, gallstones composed mostly of calcium allodeoxycholyl glycine are induced by the feeding of 5β-cholestan-3β-ol. In the taurine-deficient rat, the feeding of lithocholate leads to formation of gallstones which contain a mixture of calcium lithocholyl glycine and 3α,6β-dihydroxy cholanoyl glycine. These animal models may be of value in testing agents designed to lower calcium activity in bile.