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Papers In Press, published online ahead of print August 16, 2002
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Submitted on July 26, 2002
Department of Medicine, Gastroenterology Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215
Corresponding Author: dqwang{at}caregroup.harvard.edu
This study investigated whether b-muricholic acid, a natural trihydroxy hydrophilic bile acid of rodents, acts as a biliary cholesterol-desaturating agent to prevent cholesterol gallstones and if it facilitates the dissolution of gallstones compared to ursodeoxycholic acid (UDCA). For gallstone prevention study, gallstone-susceptible male C57L mice were fed 8 weeks with a lithogenic diet (2% cholesterol and 0.5% cholic acid) with or without 0.5% UDCA or b-muricholic acid. For gallstone dissolution study, additional groups of mice that have formed gallstones were fed chow with or without 0.5% b-muricholic acid or UDCA for 8 weeks. 100% of mice fed the lithogenic diet formed cholesterol gallstones. Addition of b-muricholic acid and UDCA decreased gallstone prevalence to 20% and 50% through significantly reducing biliary secretion rate, saturation index, and intestinal absorption of cholesterol, as well as inducing phase boundaries shifted and an enlarged Region E that prevented the transition of cholesterol from its liquid crystalline phase to solid crystals and stones. Eight weeks of b-muricholic acid and UDCA administration produced complete gallstone dissolution rates of 100% and 60% compared to the chow (10%). We conclude that b-muricholic acid is more effective than UDCA in treating or preventing diet-induced or experimental cholesterol gallstones in mice.
Revised on August 16, 2002
Accepted on July 31, 2002
Effect of beta-muricholic acid on the prevention and dissolution of cholesterol gallstones in C57L/J mice
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