title: In vivo effects of phenylbutazone on inflammation and cartilage-derived biomarkers in equine joints with acute synovitis.
abstract: Although phenylbutazone (PBZ) is commonly used in equine orthopaedic practice, little is known about its in vivo effects on joint inflammation and cartilage turnover. This study investigates the effects of PBZ on inflammatory parameters, matrix metalloproteinase (MMP) activity and cartilage biomarkers in equine joints with acute synovitis. In a two-period cross-over study, transient synovitis was induced at T = 0 h in the middle carpal joint of seven ponies by lipopolysaccharide (LPS) injection. Ponies received PBZ (2 mg/kg PO twice daily) or placebo for 1 week, starting at T = 2 h. Arthroscopic assessment of the middle carpal joint was performed at T = -504, 48 and 672 h. Synovial fluid (SF) was sampled at T = -504, 0, 8, 24, 48, 168, 336 and 672 h and analysed for leukocytes and total protein, substance P, general MMP activity, glycosaminoglycans (GAG), collagen II cleavage marker C2C and synthesis marker CPII. Markers in PBZ- vs. placebo-treated joints were compared over time using a linear mixed model. LPS injection caused marked transient synovitis without visible cartilage changes. Substance P and general MMP activity were not significantly reduced by PBZ treatment, nor were SF GAG or C2C concentrations at any time point. Concentration of CPII was significantly lower at T = 24 and 168 h in PBZ treated joints compared to placebo. Although PBZ is clinically effective in treating acute synovitis, it does not limit inflammation-induced cartilage catabolism and may transiently reduce collagen anabolism as evidenced by SF markers.
authors.affiliation: Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 114, 3584 CM Utrecht, The Netherlands. Electronic address: j.c.degrauw@uu.nl.
authors.forename: J C
authors.initials: JC
authors.lastname: de Grauw
authors.affiliation: Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 114, 3584 CM Utrecht, The Netherlands.
authors.forename: J P A M
authors.initials: JP
authors.lastname: van Loon
authors.affiliation: Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 2, 3584 CM Utrecht, The Netherlands.
authors.forename: C H A
authors.initials: CH
authors.lastname: van de Lest
authors.affiliation: Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 114, 3584 CM Utrecht, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Brunott
authors.affiliation: Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 114, 3584 CM Utrecht, The Netherlands.
authors.forename: P R
authors.initials: PR
authors.lastname: van Weeren
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D006734:Horse Diseases / Q000139:chemically induced / Q000188:drug therapy*; D006736:Horses; D007270:Injections, Intra-Articular / Q000662:veterinary; D010653:Phenylbutazone / Q000627:therapeutic use*; D011509:Proteoglycans / Q000378:metabolism; D013373:Substance P / Q000378:metabolism; D013582:Synovial Fluid / Q000378:metabolism*; D013585:Synovitis / Q000139:chemically induced / Q000188:drug therapy / Q000662:veterinary*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D024043:Collagen Type II; D011509:Proteoglycans; D013373:Substance P; D010653:Phenylbutazone
keywords: Cartilage; Horse; Marker; Phenylbutazone; Synovitis