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Effects of anti-inflammatory drugs on lipopolysaccharide-challenged and -unchallenged equine synovial explants
Authors:Moses V S  Hardy J  Bertone A L  Weisbrode S E
Institution:The College of Veterinary Medicine, The Ohio State University, Columbus 43210, USA.
Abstract:OBJECTIVE: To evaluate the effects of anti-inflammatory drugs on lipopolysaccharide (LPS)-challenged and -unchallenged equine synovial membrane in terms of production of prostaglandin E2 (PGE2) and hyaluronan, viability, and histomorphologic characteristics. SAMPLE POPULATION: Synovial membranes were collected from the carpal, tarsocrural, and femoropatellar joints of 6 adult horses. PROCEDURE: Synovial membranes from each horse were minced and pooled and explants were treated with one of the following: no drug (control), drug, LPS alone, or LPS and drug. Treatment drugs were phenylbutazone (PBZ), flunixin meglumine (FNX), ketoprofen (KET), carprofen (CRP), meloxicam (MEL), low-concentration methylprednisolone (METH), high-concentration METH, dimethyl sulfoxide (DMSO), or an experimental COX-2 inhibitor (dissolved in DMSO). Following 48 hours of culture, medium was assayed for PGE2 and hyaluronan concentration. Synovial explants were assessed for viability and histomorphologic characteristics. RESULTS: For the LPS-challenged explants, PBZ, FNX, KTP CRF MEL, and low-concentration METH suppressed PGE2 production, compared with LPS challenge alone. Only MEL suppressed PGE2 production from LPS-challenged explants, compared with unchallenged explants. Synovial explants maintained > 90% viability and there was no significant difference in viability or hyaluronan production among explants. Histomorphologic scores were significantly decreased for explants treated with low-concentration METH or DMSO. CONCLUSIONS AND CLINICAL RELEVANCE: PBZ, FNX, KTP, CRFP MEL, and low-concentration METH suppressed PGE2 production in LPS-challenged explants. Meloxicam appeared to have more selective suppression of COX-2 activity. Histomorphologic scores suggest detrimental effects of METH, DMSO, and the experimental COX-2 inhibitor. Commonly used nonsteroidal anti-inflammatory drugs suppress induced synovial membrane PGE2 production without detrimental effects on synovial membrane viability and function.
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