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Journal of Lipid Research, Vol. 43, 1960-1968, November 2002
Copyright © 2002 by Lipid Research, Inc.

Effect of ß-muricholic acid on the prevention and dissolution of cholesterol gallstones in C57L/J mice¹

David Q-H. Wang^2,* and Susumu Tazuma

^* Department of Medicine, Gastroenterology Division, Beth Israel Deaconess Medical Center, Harvard Medical School and Harvard Digestive Diseases Center, Boston MA
First Department of Internal Medicine, Hiroshima University School of Medicine, Hiroshima, Japan

² To whom correspondence should be addressed. e-mail: dqwang{at}caregroup.harvard.edu

This study investigated whether ß-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 with 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 ß-muricholic acid. For gallstone dissolution study, additional groups of mice that have formed gallstones were fed chow with or without 0.5% ß-muricholic acid or UDCA for 8 weeks. One hundred percent of mice fed the lithogenic diet formed cholesterol gallstones. Addition of ß-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 boundary shift and an enlarged Region E that prevented the transition of cholesterol from its liquid crystalline phase to solid crystals and stones. Eight weeks of ß-muricholic acid and UDCA administration produced complete gallstone dissolution rates of 100% and 60% compared with the chow (10%).

We conclude that ß-muricholic acid is more effective than UDCA in treating or preventing diet-induced or experimental cholesterol gallstones in mice.

Abbreviations: CSI, cholesterol saturation index; HPLC, high performance liquid chromatography; UDCA, ursodeoxycholic acid

Supplementary key words bile flow • phospholipid • intestinal cholesterol absorption • phase diagram

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