Effect of beta-muricholic acid on the prevention and dissolution of cholesterol gallstones in C57L/J mice.
This study investigated whether beta-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 beta-muricholic acid. For gallstone dissolution study, additional groups of mice that have formed gallstones were fed chow with or without 0.5% beta-muricholic acid or UDCA for 8 weeks. One hundred percent of mice fed the lithogenic diet formed cholesterol gallstones. Addition of beta-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 beta-muricholic acid and UDCA administration produced complete gallstone dissolution rates of 100% and 60% compared with the chow (10%). We conclude that beta-muricholic acid is more effective than UDCA in treating or preventing diet-induced or experimental cholesterol gallstones in mice.
Wang
David Q-H
DQ
Department of Medicine, Gastroenterology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. dqwang@caregroup.harvard.edu
Tazuma
Susumu
S
D000818:Animals; D001647:Bile Acids and Salts / Q000737:chemistry / Q000378:metabolism; D001652:Bile Ducts / Q000503:physiopathology; D002769:Cholelithiasis / Q000378:metabolism* / Q000517:prevention & control*; D002784:Cholesterol / Q000378:metabolism*; D002793:Cholic Acids / Q000494:pharmacology*; D004195:Disease Models, Animal; D007408:Intestinal Absorption; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010316:Particle Size
D001647:Bile Acids and Salts; D002793:Cholic Acids; C004821:muricholic acid; D002784:Cholesterol