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

被引:49
作者
Wang, DQH [1 ]
Tazuma, S
机构
[1] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Gastroenterol Div, Boston, MA 02115 USA
[2] Harvard Digest Dis Ctr, Boston, MA USA
[3] Hiroshima Univ, Sch Med, Dept Internal Med 1, Hiroshima 730, Japan
关键词
bile flow; phospholipid; intestinal cholesterol absorption; phase diagram;
D O I
10.1194/jlr.M200297-JLR200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 P-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.
引用
收藏
页码:1960 / 1968
页数:9
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