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Effect of chitinase inhibitors on endotoxin-induced uveitis (EIU) in rabbits

Bucolo, Claudio and Musumeci, Maria and Maltese, Adriana and Drago, Filippo and Musumeci, Salvatore (2008) Effect of chitinase inhibitors on endotoxin-induced uveitis (EIU) in rabbits. Pharmacological Research, Vol. 57 (3), p. 247-252. ISSN 1043-6618. Article.

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DOI: 10.1016/j.phrs.2008.02.002

Abstract

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 100 ng/10 μl lipopolysaccharide (LPS). Drugs at four different concentrations (0.1, 0.01, 0.001 and 0.0001 mM) were topically applied to the rabbit eye five times in 24 h. Tears were collected at 0, 6 and 24 h 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 24 h 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 24 h 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.

Item Type:Article
ID Code:2008
Status:Published
Refereed:Yes
Uncontrolled Keywords:Uveitis, endotoxin, chitinase, rabbit
Subjects:Area 06 - Scienze mediche > MED/38 Pediatria generale e specialistica
Divisions:001 Università di Sassari > 01 Dipartimenti > Neuroscienze, scienze materno infantili
002 Altri enti e centri di ricerca del Nord Sardegna > CNR-Consiglio Nazionale delle Ricerche > Istituto di chimica biomolecolare, Sassari
Publisher:Academic Press / Elsevier
ISSN:1043-6618
Copyright Holders:© 2008 Elsevier
Deposited On:18 Aug 2009 10:06

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