The preventive effect of 3 alpha, 7 beta, 12 alpha-trihydroxy-5 beta-
cholanoic acid (
ursocholic acid) and
ursodeoxycholic acid on the formation of biliary
cholesterol crystals was studied in mice.
Cholesterol crystals developed with 80% incidence after feeding for five weeks a lithogenic diet containing 0.5%
cholesterol and 0.25%
sodium cholate. When 0.25%
ursocholic acid or
ursodeoxycholic acid was added to the lithogenic diet, the incidence as well as the grade (severity) of the
gallstones were reduced. Plasma and liver
cholesterol levels were decreased by
ursodeoxycholic acid but not by
ursocholic acid. Gallbladder
cholesterol and
phospholipid levels were decreased by both
bile acids. The biliary
bile acid level was decreased by
ursocholic acid but not by
ursodeoxycholic acid. After feeding
ursocholic acid, its level in the bile was about 25% and the levels of
cholic acid and
beta-muricholic acid decreased. Fecal
sterol excretion was not changed by
ursocholic acid, but was increased by
ursodeoxycholic acid. After feeding
ursocholic acid, fecal excretion of
deoxycholic acid,
cholic acid, and
ursocholic acid increased. No differences were found between mice, with or without
gallstones, in plasma and liver
cholesterol levels, biliary
phospholipid and
bile acid levels, fecal
sterol and
bile acid levels, and biliary and fecal
bile acid composition. The results suggest that the lower incidence of crystal formation
after treatment with
ursocholic acid is probably by a different mechanism than with
ursodeoxycholic acid. In the mouse model,
ursodeoxycholic acid exerts its effect at least partially, by decreasing
cholesterol absorption.
Ursocholic acid is well absorbed and excreted into bile and transformed into
deoxycholic acid by the intestinal microflora in mice.