Resveratrol, SC-560, Selective COX-1 Inhibitors, and the Non-Selective COX Inhibitor- Ketorolac Inhibit Rabbit Aqueous PGE2 Formation Following Paracentresis: Whereas the Selective COX-2 Inhibitor- Nimesulide Was Inactive

Abstract

Purpose: : To evaluate the roles of COX-1 and COX-2 in the early phase of the inflammatory response post surgical intervention in a rabbit model of ocular inflammation.

Methods: : : The ability of both selective and non-selective COX-1 and COX-2 agents to reduce the inflammatory response following surgical manipulation was compared using the selective COX-1 inhibitors resveratrol (3,5,4’-trihydroxy-trans-stilbene) 0.1% and SC-560 (0.1%), the selective COX-2 inhibitor nimesulide (0.1%), and the non-selective COX-1 and COX-2 inhibitor, ketorolac (0.4%) . The study agents were dosed one (1) drop in the right eye (50 µl) of rabbits, and vehicle containing 0.5% carboxymethyl cellulose was dosed one (1) drop in the left eye (50 µl). Vehicle was also dosed to both eyes of a separate control group. One hour after dosing, a paracentresis puncture was made in the peripheral cornea of both eyes. Aqueous humor was collected from both eyes after 1 hour. Concentrations of PGE₂ were determined by immunoassay, after a 1:10 dilution.

Results: : The selective COX-1 inhibitors- resveratrol (N=5) and SC-560 (N=5) significantly inhibited (48% Inhibition (I), p = 0.015; 46% I, p = 0.016 respectively) the inflammatory response compared to the vehicle treated eyes in both the vehicle treated group, and the contralateral eyes. The non-selective COX inhibitor- ketorolac (n=3) also inhibited the inflammatory response (80% I). The COX-2 selective drug- nimesulide (n=5) did not significantly inhibit (16% I, p = 0.18) the increase in PGE₂ concentrations

Conclusions: : Inflammation as measured by PGE₂ concentrations following paracentresis can be attenuated by the COX-1 selective agents-resveratrol, SC-560, the mixed inbibitor- ketorolac, but not by the COX-2 selective agent- nimesulide. Resveratrol (0.1%), SC-560 (0.1%), and ketorolac (0.4%) all significantly inhibit PGE₂ synthesis following paracentresis; whereas the COX-2 selective agent- nimesulide was inactive. This suggests that COX-1, but not COX-2 activity is implicated in the early inflammatory process.

Keywords: inflammation • anterior chamber • cytokines/chemokines