Effects of Intravenous Administration of FR122047 (a Selective Cyclooxygenase 1 Inhibitor) and FR188582 (a Selective Cyclooxygenase 2 Inhibitor) on Prostaglandin-E2-Induced Aqueous Flare Elevation in Pigmented Rabbits

Abstract

Purpose: Two isoforms of cyclooxygenase (COX-1 and COX-2) exist. To determine in vivo effects of the intravenous administration of FR122047 (a selective COX-1 inhibitor), FR188582 (a selective COX-2 inhibitor), diclofenac sodium or dexamethasone phosphate disodium on prostaglandin-E₂ (PGE₂)-induced aqueous flare elevation and mRNA levels for COX-1 and COX-2 in pigmented rabbits. Methods: To produce aqueous flare elevation in rabbits, PGE₂, 25 µg/ml, was applied to the cornea with the use of a glass cylinder. FR122047, FR188582, diclofenac sodium or dexamethasone phosphate disodium was intravenously injected before PGE₂ application. Aqueous flare was measured with a laser flare-cell meter. The mRNA levels for COX-1 and COX-2 in the iris-ciliary body were determined by real-time polymerase chain reaction. Results: FR122047, FR188582 and diclofenac sodium (15 µmol/kg each) injected intravenously 30 min before PGE₂ application inhibited 29 ± 5, 40 ± 12 and 50 ± 9% of aqueous flare elevation, respectively. Simultaneous injection of FR122047 (15 µmol/kg) and FR188582 (15 µmol/kg) 30 min before PGE₂ application inhibited 61 ± 8% of flare elevation. Dexamethasone phosphate disodium (15 µmol/kg) injected intravenously 300 min before PGE₂ application inhibited 68 ± 8% of aqueous flare elevation. Less than 3-fold changes in mRNA levels for COX-1 and COX-2 in the iris-ciliary body were noted after PGE₂, FR122047, FR188582, diclofenac sodium or dexamethasone phosphate disodium treatment. Conclusion: It is possible that enzyme activities of both COX-1 and COX-2 may be involved in the mechanism of PGE₂-induced aqueous flare elevation in pigmented rabbits.