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Veterinary journal (London, England : 1997)2014; 201(1); 51-56; doi: 10.1016/j.tvjl.2014.03.030

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.
Publication Date: 2014-04-01 PubMed ID: 24888681DOI: 10.1016/j.tvjl.2014.03.030Google Scholar: Lookup
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  • Journal Article
  • Randomized Controlled Trial

Summary

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The researchers’ study looks at the effect of phenylbutazone on joint inflammation and cartilage in ponies with acute synovitis. While the drug alleviated symptoms, it didn’t appear to limit inflammation-induced cartilage breakdown and may have temporarily reduced collagen production.

Research Methodology

  • The investigation was designed as a two-period cross-over study involving seven ponies.
  • Acute joint inflammation, known as synovitis, was induced through the injection of lipopolysaccharides (LPS), a type of bacterial toxin, into the middle carpal joint of the ponies.
  • The ponies were then treated with phenylbutazone or placebo twice a day orally for a period of one week.
  • Arthroscopic examination of the middle carpal joint was carried out at specified time intervals, as well as the collection of synovial fluid for analysis.
  • The synovial fluid was analysed for several biomarkers related to inflammation and cartilage turnover, including leukocytes, total protein, substance P, general metalloproteinase (MMP) activity, glycosaminoglycans (GAG), and collagen markers.

Results and Findings

  • The LPS injection effectively caused temporary synovitis, but did not induce observable cartilage changes.
  • Despite the clinical efficiency of phenylbutazone in treating acute synovitis, it did not significantly reduce inflammation-triggered cartilage catabolism.
  • The general MMP activity, substance P, SF GAG, or C2C concentrations were not notably reduced by phenylbutazone treatment.
  • Comparing placebo-treated joints to phenylbutazone-treated joints, the concentration of CPII (a biomarker indicating collagen synthesis) was found to be significantly lower at 24 and 168 hours following treatment in the joints treated with phenylbutazone.

Concluding Observations

  • While phenylbutazone is effective clinically in easing the symptoms of acute synovitis, it does not appear to minimise the breakdown of cartilage induced by inflammation.
  • Furthermore, the evidence from synovial fluid markers suggests that phenylbutazone may cause a temporary slowdown in the anabolic process of collagen production in the joints.

Cite This Article

APA
de Grauw JC, van Loon JP, van de Lest CH, Brunott A, van Weeren PR. (2014). In vivo effects of phenylbutazone on inflammation and cartilage-derived biomarkers in equine joints with acute synovitis. Vet J, 201(1), 51-56. https://doi.org/10.1016/j.tvjl.2014.03.030

Publication

ISSN: 1532-2971
NlmUniqueID: 9706281
Country: England
Language: English
Volume: 201
Issue: 1
Pages: 51-56
PII: S1090-0233(14)00130-0

Researcher Affiliations

de Grauw, J C
  • Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 114, 3584 CM Utrecht, The Netherlands. Electronic address: j.c.degrauw@uu.nl.
van Loon, J P A M
  • Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 114, 3584 CM Utrecht, The Netherlands.
van de Lest, C H A
  • Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 2, 3584 CM Utrecht, The Netherlands.
Brunott, A
  • Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 114, 3584 CM Utrecht, The Netherlands.
van Weeren, P R
  • Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 114, 3584 CM Utrecht, The Netherlands.

MeSH Terms

  • Administration, Oral
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Biomarkers / metabolism
  • Collagen Type II / metabolism
  • Horse Diseases / chemically induced
  • Horse Diseases / drug therapy
  • Horses
  • Injections, Intra-Articular / veterinary
  • Phenylbutazone / therapeutic use
  • Proteoglycans / metabolism
  • Substance P / metabolism
  • Synovial Fluid / metabolism
  • Synovitis / chemically induced
  • Synovitis / drug therapy
  • Synovitis / veterinary
  • Time Factors
  • Treatment Outcome

Citations

This article has been cited 16 times.
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