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Anna Enzsoly, Romana Zelko, Miklos Toth, Peter Matyus, Janos Nemeth, David A. Ammar, J. M. Petrash; Anti-inflammatory Effect Of A Novel VAP-1 Inhibitor Molecule In Uveitis. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3224.
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The aim of this study was to evaluate the effects of VAP-1 inhibitors on a mouse model of uveitis.
Uveitis was induced in mice (n=20) with a single intraperitoneal injection of lipopolysaccharide. The animals were randomly divided into different treatment groups. Group 1 as a control group received vehicle, group 2 and 3 were treated with different doses of a specific VAP-1 inhibitor LJP 1207 [N-(2-phenylallyl)hydrazine hydrochloride], group 4 was treated with our own VAP-1 inhibitor [3-(3,4-diphenyl-1,3-oxazol-2-yl)propanal oxime, SzV-1287]. 24 hours later, mice were sacrificed. Severity of the uveitis was assessed based on the number of inflammatory cells in the vitreous cavity and the anterior chamber, on sections passing through the optic nerve, stained with hematoxylin-eosin. ANOVA test was used for statistical analysis, and the differences between the groups were evaluated using Fisher post hoc test.
Histopathological images showed a marked inflammatory response in the vehicle-treated group (average cell number±SD: 40.15±8.525). Treatment with our novel VAP-1 inhibitor resulted a significant suppression of inflammation according to the vehicle-treated group (p<0.019) and to LJP 1207 treated group (p<0.03). However, there was no significant difference between the anti-inflammatory effects of high-dose LJP 1207 and the vehicle-treated group (p>0.6).
In this uveitis model, our novel VAP-1 inhibitor showed a highly significant anti-inflammatory effect. We have also demonstrated that it was more effective than the reference VAP-1 inhibitor LJP 1207, therefore it may have therapeutic potentials for inflammatory eye diseases.
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