title: Preferential and non-selective cyclooxygenase inhibitors reduce inflammation during lipopolysaccharide-induced synovitis.
abstract: Synovitis in horses is frequently treated by administration of non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit cyclooxygenase isoforms (COX-1 and COX-2). Constitutively expressed COX-1 is involved in physiologic functions such as maintenance of gastric mucosal integrity, whereas COX-2 is up-regulated at sites of inflammation. Thus, COX-2 inhibitors reduce inflammation with reduced gastrointestinal side effects as compared to non-selective COX inhibitors. The objective of the present study was to compare the anti-inflammatory effects of the preferential COX-2 inhibitor etodolac with the non-selective COX inhibitor phenylbutazone in horses with lipopolysaccharide (LPS)-induced synovitis. Three groups of horses (n=6) received no treatment, phenylbutazone (4.4 mg/kg, IV, q12h), or etodolac (23 mg/kg, IV, q12h), respectively, 2-h following injection of LPS into one middle carpal joint. Synovial fluid was analyzed for white blood cell (WBC) count, and TXB2 and PGE2 levels. Phenylbutazone and etodolac significantly reduced WBC count 6 and 24-h following injection of LPS compared to untreated horses. In addition, both drugs significantly reduced PGE2 levels (P<0.05) 6-h following LPS injection, whereas the probable COX-1 prostanoid TXB2 was significantly reduced by phenylbutazone (P<0.05), but not etodolac. Etodolac may serve as a more selective anti-inflammatory agent than phenylbutazone for treatment of equine synovitis.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606, USA.
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Morton
authors.forename: Nigel B
authors.initials: NB
authors.lastname: Campbell
authors.forename: J'mai M
authors.initials: JM
authors.lastname: Gayle
authors.forename: W Rich
authors.initials: WR
authors.lastname: Redding
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Blikslager
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay / Q000662:veterinary; D017308:Etodolac / Q000494:pharmacology*; D006734:Horse Diseases / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D006736:Horses; D007958:Leukocyte Count / Q000662:veterinary; D008070:Lipopolysaccharides; D010653:Phenylbutazone / Q000494:pharmacology*; D011897:Random Allocation; D013582:Synovial Fluid / Q000737:chemistry; D013585:Synovitis / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology / Q000662:veterinary*; D020825:T-Box Domain Proteins / Q000032:analysis
chemical_list: D000893:Anti-Inflammatory Agents; D016861:Cyclooxygenase Inhibitors; D008070:Lipopolysaccharides; C097348:T-Box Domain Protein 2; D020825:T-Box Domain Proteins; D017308:Etodolac; D010653:Phenylbutazone; D015232:Dinoprostone