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Role of cyclooxygenase (COX)‐1 and COX‐2 in a rabbit model of lipopolysaccharide (LPS)‐induced ocular inflammation
Author(s) -
Waterbury L. David
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb512
Subject(s) - nimesulide , ketorolac , cyclooxygenase , pharmacology , inflammation , chemistry , prostaglandin , lipopolysaccharide , medicine , endocrinology , immunology , analgesic , biochemistry , enzyme
Objective To evaluate relative contribution of COX‐1 and COX‐2 to the LPS‐induced ocular inflammation in rabbits. Methods At hour 0, 27 rabbits received either artificial tears (Refresh Tears ® ; Allergan, Inc.; Irvine, CA) (3 drops 20 min apart), COX‐1 inhibitors trans ‐resveratrol 0.1% (TR) (3 drops 20 min apart) or FR122047 0.1% (FR) (1 drop), COX‐2 inhibitor nimesulide 0.1% (1 drop), or COX‐1 and COX‐2 inhibitor ketorolac 0.45% (Acuvail ® ; Allergan, Inc.; Irvine, CA) (3 drops 20 min apart). At hour 1, rabbits received intravenous injections of LPS and fluorescein isothiocyanate (FITC)‐dextran. At hour 2, aqueous samples were collected for analysis. Six additional rabbits received only FITC‐dextran 2 hours before sample collection. Results LPS increased aqueous prostaglandin E 2 (PGE 2 ) and FITC‐dextran levels by 4.2‐ and 137.8‐fold, respectively. Ketorolac 0.45% and COX‐1 inhibitors (TR and FR) significantly reduced PGE 2 elevation ( P < .01) while COX‐2 inhibitor (nimesulide) was ineffective. Of all inhibitors, only ketorolac 0.45% significantly inhibited FITC‐dextran elevation ( P < .01). Inefficacy of TR and FR in reducing FITC‐dextran leakage may be due to their poor penetration into iris–ciliary body. Conclusion COX‐1 was the primary isoenzyme responsible for early inflammatory response to LPS. Ketorolac 0.45% suppressed ocular inflammation by inhibiting PGE 2 elevation and FITC‐dextran leakage.