Effects of bile acid oxazolines on gallstone formation in prairie dogs.
The effects of 2 bile acid analogs, chenodeoxy-oxazoline [2-(3 alpha, 7 alpha-dihydroxy-24-nor-5 beta-cholanyl)-4,4-dimethyl-2-oxazoline] and ursodeoxy-oxazoline [2-(3 alpha, 7 beta-dihydroxy-24-nor-5 beta-cholanyl)-4,4-dimethyl-2-oxazoline] were examined in the prairie dog model of cholesterol cholelithiasis. Gallstones and biliary cholesterol crystals were induced in 5 out of 6 male prairie dogs fed a semisynthetic diet containing 0.4% cholesterol for 8 weeks. Six animals maintained on a low cholesterol control diet (0.08% cholesterol) exhibited neither gallstones nor biliary cholesterol crystals. The addition of 0.06% chenodeoxy-oxazoline to the lithogenic diet did not prevent induced cholelithiasis or the appearance of cholesterol crystals in bile. In contrast, 0.06% dietary ursodeoxy-oxazoline prevented gallstones in 5 out of 6 prairie dogs (but cholesterol crystals were present in the bile of 4 of these animals). Histologically, most of the livers from the prairie dogs fed the cholesterol-supplemented semisynthetic diet showed bile duct proliferation, inflammatory infiltration and fibrosis along the portal tracts. These pathologic changes were generally not ameliorated by adding chenodeoxy-oxazoline or chenodeoxy-oxazoline plus chenodeoxycholic acid to the diet. Portal tract pathology was markedly reduced in most animals by adding ursodeoxy-oxazoline to the cholesterol-supplemented diet. The pathologic changes overall could best be correlated with the presence of gallstones, but not with the incidence of biliary cholesterol crystals.
D000818:Animals; D001646:Bile / Q000378:metabolism; D001647:Bile Acids and Salts / Q000494:pharmacology; D001835:Body Weight; D002757:Cholanes / Q000494:pharmacology*; D002769:Cholelithiasis / Q000209:etiology* / Q000517:prevention & control; D002784:Cholesterol / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000009:adverse effects; D004435:Eating; D005243:Feces / Q000032:analysis; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects; D008297:Male; D012589:Sciuridae
D001647:Bile Acids and Salts; D002757:Cholanes; D002791:Cholesterol, Dietary; C037265:chenooxazoline; D002784:Cholesterol