A novel 5-lipoxygenase inhibitor prevents gallstone formation in a lithogenic prairie dog model.
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.
Kam
D M
DM
Michigan State University/Butterworth Hospital, Grand Rapids, 49503, USA.
Webb
P A
PA
Sandman
G
G
Chugh
A
A
Vertz
M L
ML
Scheeres
D E
DE
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
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D002784:Cholesterol; D001241:Aspirin