The Korean Society of Gastroenterology& SLDDS 2021 : Slide Session ; K-BP-11 : Pancreatobiliary ; Eicosapentaenoic Acid Dissolves Cholesterol Gallstones by Attenuating Cholesterol Saturation and Suppressing Mucin Production in Mice

Background: The increasing prevalence of cholesterol gallstone (CG) disease has become an economic burden to the healthcare system. Ursodeoxycholic acid (UDCA) is the only established medical agent used to dissolve gallstones. In investigating novel therapeutics for CG, we assessed the therapeutic effects of eicosapentaenoic acid (EPA), which is one of most bioactive omega-3 polyunsaturated fatty acids, on CG induced by feeding a lithogenic diet (LD) containing high cholesterol levels to mice. Methods: Mice were divided into the following four groups: (A) LD; (B) LD+EPA; (C) LD+UDCA; (D) LD+EPA+UDCA. After LD feeding for 10 weeks, EPA or UDCA was administered orally and the diet maintained for 16 weeks. The levels of phospholipids and cholesterol in bile, CG dissolution, gallbladder wall thickness, MUC gene expression ingallbladder were analyzed. Results: Mice in the EPA treatment (Groups B, D) showed signifi cantly higher stone dissolution than the control LD group (Groups A). The combination treatment of EPA and UDCA accelerate stone dissolution more than mono-therapy with EPA or UDCA. Bile phospholipid levels were signifi cantly elevated and cholesterol saturation index was decreased in the Group B. Although hypertrophy of the gallbladder wall was evident in mice fed LD, the wall thickness of gallbladder in mice treated with EPA (Group B, D) was signifi cantly thinner than in mice fed LD. MUC 2, 5ac, 5b and 6 mRNA expression levels were signifi cantly elevated in the LD-fed group, and this was suppressed by EPA with or without UDCA. Conclusions: EPA dissolves cholesterol gallstone in mouse through increasing the levels of bile phospholipids, decreasing cholesterol saturation and suppressing bile mucin formation. Further human study is required to investigate the therapeutic effects of EPA in patients with CG.