title: A novel 5-lipoxygenase inhibitor prevents gallstone formation in a lithogenic prairie dog model.
abstract: Gallstone formation is dependent on biliary cholesterol supersaturation, the pronucleating effects of gallbladder mucin, and inflammation. We evaluated the effect of aspirin (ASA) and a 5-Lipoxygenase inhibitor (FLAPI) on cholesterol precipitation and leukotriene levels in an animal model of cholesterol gallstone formation. Male prairie dogs were divided into four dietary groups: normal chow controls, 1.2 per cent cholesterol (XOL), 1.2 per cent cholesterol plus ASA (XOL + ASA, 100 mg/kg/d), and cholesterol plus FLAPI (XOL + FLAPI, 100 mg/kg/12h). At 3 weeks the subjects were anesthetized, cholecystectomy performed, and the common duct cannulated for bile sampling. Cholesterol precipitation, lithogenic indices, and leukotriene content were analyzed. The group XOL + FLAPI did not form cholesterol crystals, whereas the group XOL + ASA did (P < 0.05, Fisher's exact test). All cholesterol-fed groups had significantly increased lithogenic indices when compared to controls. The XOL + FLAPI group showed a significant and paradoxical increase in LTB4 compared to the other groups (P < 0.05, ANOVA, Fisher's PLSD). This study has shown a significant decrease in the rate of cholesterol stone formation through the use of a novel leukotriene inhibitor at high doses, despite a high cholesterol diet.
authors.affiliation: Michigan State University/Butterworth Hospital, Grand Rapids, 49503, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Kam
authors.forename: P A
authors.initials: PA
authors.lastname: Webb
authors.forename: G
authors.initials: G
authors.lastname: Sandman
authors.forename: A
authors.initials: A
authors.lastname: Chugh
authors.forename: M L
authors.initials: ML
authors.lastname: Vertz
authors.forename: D E
authors.initials: DE
authors.lastname: Scheeres
mesh_terms: D000818:Animals; D001241:Aspirin / Q000627:therapeutic use; D002769:Cholelithiasis / Q000378:metabolism* / Q000517:prevention & control*; D002784:Cholesterol / Q000032:analysis; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D015289:Leukotrienes / Q000096:biosynthesis; D016859:Lipoxygenase Inhibitors; D008297:Male; D012589:Sciuridae
chemical_list: D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D002784:Cholesterol; D001241:Aspirin