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L David Waterbury; Lack of Correlation between PGE2 levels and Blood Aqueous Barrier Inhibition in a rabbit model of ocular inflammation. Invest. Ophthalmol. Vis. Sci. 2013;54(15):118.
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In a model of ocular inflammation, several topical NSAIDs were simultaneously tested for inhibition of PGE2 and for blood aqueous barrier breakdown following LPS administration. The purpose of the study was to determine if inhibition of PGE2 concentrations was correlated with inhibition of the breakdown of the blood aqueous barrier following the dosing with topical NSAIDs.
Topical dosing of suspensions (0.1% FR122047, 0.1% trans-resveratrol) or solutions (0.1% amfenac, 0.09% bromfenac, 0.1 % diclofenac, 0.4% ketorolac) of NSAIDs were administered to one eye of New Zealand White Rabbits (n=6). Rabbits received LPS (Salmonella enterica typhimurium, 10 µg/kgm), and fluorescein isothiocyanate-dextran (FITC-dextran), M.W. = ~70,000, 30 mg/kgm, iv, at 1 hour). FITC-dextran was used to determine the blood aqueous leakage. At 2 hours after topical dosing , aqueous humor samples were simultaneously analyzed for PGE2 and FITC-dextran concentrations.
All test drugs significantly inhibited PGE2 concentrations in the aqueous humor. The degree on PGE2 inhibition ranged from ~ 50 to 97%, and the inhibition of FITC inhibition ranged from 7 to 98%. Amfenac was more effective in inhibiting FITC-dextran accumulation than PGE2 concentrations (97% vs 68% respectively). FR122047, trans-resveratrol, and diclofenac were active in lowering PGE2, but did not significantly affect FITC-dextran concentrations. Both ketorolac and bromfenac were equally active with 2 hour dosing, but with 12 hour pre-dosing, only ketorolac was active in suppressing FITC-dextran.
Taking into account COX selectivity and potency, there did not appear to be a correlation between PGE2 and FITC-dextran inhibition suggesting different sites of action for both effects.
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