LIPIDOSIS INDUCED IN THE DOG GALLBLADDER BY A DIRECT 5-LIPOXYGENASE INHIBITOR

The direct 5-lipoxygenase inhibitor L-739,010 was administered at a do se of 60 mg/kg/day per os to beagle dogs for 15 days. Histopathologica l examination of gallbladders from treated dogs showed epithelial vacu olation and submucosal infiltration by foamy macrophages that were pos itive for lipids in Sudan Black-and/or Oil Red O-stained sections. Sca nning electron microscopic examination of gallbladder mucosa showed th ickening of epithelial folds and multifocal epithelial membrane disrup tions. Transmission electron microscopy confirmed these findings and s howed mucosal epithelial cell lipid droplet accumulation and submucosa l infiltration of macrophages filled with lipid droplets, myelin figur es, heterophagosomes, and cholesterol clefts. These changes resembled those reportedly seen in the human gallbladder with cholesterolosis an d/or chronic cholecystitis.