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.

Effects of meloxicam administered by different routes to control experimental uveitis in dogs

“…In addition, the NSAID (tepoxalin) used in that study was administered one hour before paracentesis (GILMOUR & LEHENBAUER, 2006). HAYASAKA et al (2003) and ABE et al (2004) demonstrated that topical or intravenous administration of nonsteroidal antiinflammatory drugs are able to suppress the protein influx to aqueous humor, only when used one hour and a half before the blood-aqueous barrier breakdown.…”

“…Nonsteroidal anti-inflammatory drugs suppress the protein influx to aqueous humor, after one hour and a half, whereas corticosteroids may need six hours after administration to show action by inhibitory effects on expression of the messenger RNAencoding cyclooxygenases-related protein (HAYASAKA et al, 2003;ABE et al, 2004). The reduction of only 27% in protein levels, contrasts the observations of a previous study, which proved that topical flurbiprofen, diclofenac, and suprofen were effective at preventing blood-aqueous barrier disruption after paracentesis in dogs (WARD, 1996).…”

The Role of Cyclooxygenase-1 and -2 in Sevoflurane-Induced Postconditioning Against Myocardial Infarction

“…16 Potential unselective intrinsic effects of SC-560 on other components in the signaling cascade thus remain speculative. However, SC-560 is a frequently used inhibitor in rodent reperfusion-injury studies, and other selective COX-1 inhibitors like FR122047 33 and mofezolac 34 have not been tested. One might further speculate that selective COX-1 inhibition leads to a shift of the thromboxane/prostaglandin balance toward the prostaglandins, which in turn causes vasodilatation of coronary arteries.…”