Combination of a cyclooxygenase inhibitor and a nitric oxide synthase inhibitor in the treatment of experimental uveitis

ABSTRACT

Multiple factors and mediators interact to modulate the inflammatory process. In the present study, roles of nitric oxide [NO] and prostagl and in E[2] [PGE[2]] together with their simultaneous inhibition are investigated in a model of induced anterior uveitis in rabbits. Six groups of animals served as controls. Anterior uveitis was induced in 4 groups by intravitreal injection of 10 micro l complete Freund's adjuvant. One group was left untreated and the other three groups were treated three times daily for 14 days with N[G]-nitro-L-arginine methyl ester [L-NAME] 0.1% eye drops or with diclofenac 0.1% eye drops or with both drugs. Severity of uveitis was evaluated by clinical scoring at days 2, 7 and 14. On day 14, biochemical analysis of aqueous humor samples was performed for total proteins, albumin, nitrite and PGE[2]- Histopathological examination for iris and ciliary body was also done. Induction of uveitis caused elevation of clinical scores, elevation of the biochemically analyzed parameters and severe inflammatory signs by pathological examination. On day 14, both individual drugs and combination treatment produced significant decrease in intensity of uveitis compared to untreated animal model by all methods of evaluation. Combination treatment produced more reduction in clinical scores, more reduction in levels of total proteins, albumin and PGE[2] and also better histopathological picture compared to individual drug treatment. It can be concluded that both NO and PGE[2] are involved in the pathogenesis of Freund's adjuvant induced uveitis. Inhibition of production of both of them can improve the management of uveitis