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Effects of bile acid oxazolines on gallstone formation in prairie dogs
Author(s) -
Cohen Bertram I.,
Singhal Anil K.,
Stenger Richard J.,
MayDonath Patricia,
FinverSadowsky Judith,
McSherry Charles K.,
Mosbach Erwin H.
Publication year - 1984
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/bf02534484
Subject(s) - gallstones , cholesterol , chenodeoxycholic acid , oxazoline , prairie dog , medicine , bile acid , biliary tract , ursodeoxycholic acid , gastroenterology , clinical chemistry , endocrinology , biology , biochemistry , ecology , catalysis
The effects of 2 bile acid analogs, chenodeoxy‐oxazoline [2‐(3α,7α‐dihydroxy‐24‐nor‐5β‐cholanyl)‐4,4‐dimethyl‐2‐oxazoline] and ursodeoxy‐oxazoline [2‐(3α, 7β‐dihydroxy‐24‐nor‐5β‐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.