Effects of cloricromene,a coumarin derivative,on endotoxin-induced uveitis in Lewis rats

PURPOSE: To investigate the effects of cloricromene, a coumarin derivative, in rats subjected to endotoxin-induced uveitis (EIU). METHODS: Endotoxin uveitis was induced in male Lewis rats by a single footpad injection of 200 microg lipopolysaccharide (LPS). Cloricromene was topically applied to the rat eye twice at 1 hour before and 7 hours after injection of LPS. A separate group of animals was treated with vehicle. Rats were killed 16 hours after injection and the eyes enucleated for histologic examination and immunohistochemical analysis. The effect of treatment was also evaluated by slit lamp examination, by the number of intraocular inflammatory cells on histologic sections, and by measuring the protein and TNFalpha levels in the aqueous humor. Nitrite and nitrate production was also measured in the aqueous humor. RESULTS: The histopathology of the iris-ciliary body included inflammatory cell infiltration and nuclear modification of vessel endothelial cells. Cloricromene treatment reduced the inflammatory cell infiltration and improved histologic status of the ocular tissue. Immunohistochemical analysis for P-selectin, intracellular adhesion molecule (ICAM)-1, nitrotyrosine, and poly(ADP-ribose) synthetase (PARS) revealed a positive staining in inflammatory cell infiltration from LPS-treated rats. The degree of staining for P-selectin, ICAM-1, nitrotyrosine, and PARS was markedly reduced in tissue sections obtained from LPS-recipient rats that had received cloricromene. Cloricromene strongly inhibited cell infiltration, protein exudation, TNFalpha production, and nitrite-nitrate formation. CONCLUSIONS: This study provides the first evidence that cloricromene, a coumarin derivative, attenuates the degree of inflammation and tissue damage associated with EIU in rats.