Effect of chitinase inhibitors on endotoxin-induced uveitis (EIU) in rabbits.
The acidic mammalian chitinase (AMCase) is significantly increased in tears of human allergic conjunctivitis. The aim of the study was to investigate the effects of chitinase inhibitors, allosamidin and caffeine versus dexamethasone, in rabbit endotoxin-induced uveitis (EIU). EIU was induced in rabbits by a single intravitreal injection of 100ng/10microl lipopolysaccharide (LPS). Drugs at four different concentrations (0.1, 0.01, 0.001 and 0.0001mM) were topically applied to the rabbit eye five times in 24h. Tears were collected at 0, 6 and 24h after LPS to measure the AMCase activity. The effect of treatment was also evaluated at the same time by slit lamp examination. Tear AMCase activity increased 6 and 24h after LPS injection. The AMCase activity was significantly inhibited in all treated groups with all doses of allosamidin and caffeine except with the lowest concentration. A higher AMCase inhibition at 24h was found with allosamidin and caffeine compared to dexamethasone. Moreover, topical administration of allosamidin, caffeine and dexamethasone produced a remarkable reduction of inflammatory signs, in the order: dexamethasone>caffeine>allosamidin. AMCase inhibitors showed in this rabbit model of uveitis a notable control of inflammatory response with a significant reduction of AMCase activity in tears with caffeine and allosamidin. These results support the key role of AMCase in the pathogenesis of human ocular inflammatory diseases and the therapeutic effect of AMCase inhibitors on experimental uveitis.
Bucolo
Claudio
C
Department of Experimental and Clinical Pharmacology, School of Medicine, University of Catania, Catania, Italy.
Musumeci
Maria
M
Maltese
Adriana
A
Drago
Filippo
F
Musumeci
Salvatore
S
D000117:Acetylglucosamine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D002110:Caffeine / Q000627:therapeutic use; D002688:Chitinases / Q000037:antagonists & inhibitors*; D003907:Dexamethasone / Q000627:therapeutic use; D004731:Endotoxins / Q000633:toxicity*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D004926:Escherichia coli / Q000737:chemistry; D007700:Kinetics; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D011817:Rabbits; D013666:Tears / Q000201:enzymology; D014312:Trisaccharides / Q000627:therapeutic use; D014605:Uveitis / Q000139:chemically induced* / Q000517:prevention & control*
D000893:Anti-Inflammatory Agents; D004731:Endotoxins; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D010726:Phosphodiesterase Inhibitors; D014312:Trisaccharides; C054851:allosamidin; D002110:Caffeine; D003907:Dexamethasone; D002688:Chitinases; D000117:Acetylglucosamine