Lipidosis induced in the dog gallbladder by a direct 5-lipoxygenase inhibitor.
The direct 5-lipoxygenase inhibitor L-739,010 was administered at a dose of 60 mg/kg/day per os to beagle dogs for 15 days. Histopathological examination of gallbladders from treated dogs showed epithelial vacuolation and submucosal infiltration by foamy macrophages that were positive for lipids in Sudan Black-and/or Oil Red O-stained sections. Scanning electron microscopic examination of gallbladder mucosa showed thickening of epithelial folds and multifocal epithelial membrane disruptions. Transmission electron microscopy confirmed these findings and showed mucosal epithelial cell lipid droplet accumulation and submucosal infiltration of macrophages filled with lipid droplets, myelin figures, heterophagosomes, and cholesterol clefts. These changes resembled those reportedly seen in the human gallbladder with cholesterolosis and/or chronic cholecystitis.
Molon-Noblot
S
S
Merck Sharp & Dohme-Chibret Laboratories, Department of Safety Assessment, Riom, France.
Gillet
J P
JP
Durand-Cavagna
G
G
Huber
A C
AC
Patrick
D H
DH
Duprat
P
P
D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000633:toxicity*; D004285:Dogs; D005260:Female; D005704:Gallbladder / Q000473:pathology / Q000648:ultrastructure; D005705:Gallbladder Diseases / Q000139:chemically induced* / Q000473:pathology; D008064:Lipidoses / Q000139:chemically induced* / Q000473:pathology; D016859:Lipoxygenase Inhibitors / Q000633:toxicity*; D008297:Male; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D011804:Quinolines / Q000633:toxicity*
D001643:Bridged Bicyclo Compounds; C100577:L 739010; D016859:Lipoxygenase Inhibitors; D011804:Quinolines