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Wound collagen deposition in rats: effects of an NO‐NSAID and a selective COX‐2 inhibitor
Author(s) -
Muscará Marcelo N,
McKnight Webb,
Asfaha Samuel,
Wallace John L
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703112
Subject(s) - celecoxib , pharmacology , naproxen , wound healing , nitric oxide , chemistry , thromboxane , toxicity , prostaglandin e2 , thromboxane a2 , anti inflammatory , medicine , cyclooxygenase , biochemistry , receptor , surgery , platelet , pathology , alternative medicine , enzyme
Selective cyclo‐oxygenase (COX)‐2 inhibitors and nitric oxide‐releasing nonsteroidal anti‐inflammatory drugs (NSAIDs) exhibit reduced toxicity in the gastrointestinal tract, but may affect wound healing in other tissues. In this study, we have compared the effects of a selective COX‐2 inhibitor (celecoxib), a nitric‐oxide releasing derivative of naproxen (HCT‐3012) and naproxen in a model of wound collagen deposition in the rat. Polyvinyl alcohol sponges were implanted subcutaneously in rats. The rats were treated daily for 5 days with the test drugs at equieffective anti‐inflammatory doses. Naproxen (10 mg kg −1 ) significantly decreased (45%) collagen deposition at the wound site relative to the vehicle‐treated control group. In contrast, HCT‐3012 (14.5 mg kg −1 ) significantly increased (62%) collagen deposition, while celecoxib (10 mg kg −1 ) had no effect. Naproxen and HCT‐3012 suppressed prostaglandin (PG) E 2 levels at the wound site and whole blood thromboxane synthesis to similar degrees. Celecoxib had no significant effect on wound fluid PGE 2 levels, but slightly reduced whole blood thromboxane synthesis (by 17%). COX‐1 mRNA and protein were expressed in the wound exudate, the skin surrounding the wound and in normal skin. In contrast, COX‐2 mRNA, but not protein, was expressed in wound and normal skin. These results demonstrate that HCT‐3012 can significantly enhance collagen deposition at a wound site, despite inhibiting prostaglandin synthesis to the same extent as the parent drug. Nitric oxide‐releasing NSAIDs may represent a safer alternative to standard NSAIDs for use as anti‐inflammatory and analgesic agents by post‐surgery patients.British Journal of Pharmacology (2000) 129 , 681–686; doi: 10.1038/sj.bjp.0703112