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.
Publication Date: 2004-11-27 PubMed ID: 15563928DOI: 10.1016/j.rvsc.2004.07.006Google Scholar: Lookup
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- Comparative Study
- Journal Article
Summary
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The research examines the comparison of two anti-inflammatory drugs, etodolac and phenylbutazone, which are used to alleviate synovitis inflammation in horses. The result demonstrated that both drugs are capable of reducing inflammation, but etodolac is noted to be a more selective anti-inflammatory agent.
Introduction and Objective
- The research study centers on understanding the efficacy of two non-steroidal anti-inflammatory drugs (NSAIDs), etodolac and phenylbutazone, in treating Synovitis, a condition of inflammation of the synovial membrane, affecting horses.
- The main objective was to compare the anti-inflammatory effects of two NSAIDs. Etodolac is known to selectively inhibit cyclooxygenase isoform COX-2, involved in inflammation. On the other hand, phenylbutazone is a non-selective COX inhibitor affecting both COX-1, which helps in maintaining gastric mucosal integrity, and COX-2.
Methodology
- The study involved 3 groups of horses, each comprising of 6 members. One group was left untreated to serve as a control, while the other two received either etodolac or phenylbutazone injections after being induced with synovitis via a lipopolysaccharide (LPS) injection.
- The dosages for phenylbutazone and etodolac were 4.4 mg/kg and 23 mg/kg respectively. Synovial fluid was extracted and analyzed at two different time intervals, 6 and 24 hours post LPS injection.
Results & Findings
- The results showed that both phenylbutazone and etodolac were successful in significantly reducing white blood cell count, a known indicator of inflammation, 6 and 24 hours following the introduction of LPS, in comparison to the untreated group of horses.
- Further, both drugs also significantly decreased PGE2 levels, a biomarker for inflammation, 6 hours post LPS injection.
- An interesting outcome was that phenylbutazone resulted in a notable reduction of the probable COX-1 prostanoid TXB2, not seen in horses treated with etodolac. This indicates that etodolac doesn’t impact COX-1 as much, hence it can provide safer anti-inflammatory treatment with fewer potential side effects related to gastrointestinal disruption caused by COX-1 inhibition.
Conclusion
- The research evident that both anti-inflammatory drugs effectively reduce inflammation in horses with synovitis.
- However, as etodolac demonstrated a more targeted action towards the COX-2 pathway, with fewer side effects linked to COX-1, it could hence be suggested as the preferred treatment alternative for equine synovitis over phenylbutazone.
Cite This Article
APA
Morton AJ, Campbell NB, Gayle JM, Redding WR, Blikslager AT.
(2004).
Preferential and non-selective cyclooxygenase inhibitors reduce inflammation during lipopolysaccharide-induced synovitis.
Res Vet Sci, 78(2), 189-192.
https://doi.org/10.1016/j.rvsc.2004.07.006 Publication
Researcher Affiliations
- Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606, USA.
MeSH Terms
- Animals
- Anti-Inflammatory Agents / pharmacology
- Cyclooxygenase Inhibitors / pharmacology
- Dinoprostone / analysis
- Enzyme-Linked Immunosorbent Assay / veterinary
- Etodolac / pharmacology
- Horse Diseases / drug therapy
- Horse Diseases / enzymology
- Horse Diseases / pathology
- Horses
- Leukocyte Count / veterinary
- Lipopolysaccharides
- Phenylbutazone / pharmacology
- Random Allocation
- Synovial Fluid / chemistry
- Synovitis / drug therapy
- Synovitis / enzymology
- Synovitis / pathology
- Synovitis / veterinary
- T-Box Domain Proteins / analysis
Citations
This article has been cited 7 times.- Koziy RV, Katselis GS, Yoshimura S, Simko E, Bracamonte JL. Temporal kinetics of serum amyloid A (SAA) concentration and identification of SAA isoforms in blood and synovial fluid of horses with experimentally induced septic arthritis, non-septic synovitis, and systemic inflammation. J Vet Diagn Invest 2025 Jan;37(1):42-54.
- Mercer MA, Davis JL, McKenzie HC. The Clinical Pharmacology and Therapeutic Evaluation of Non-Steroidal Anti-Inflammatory Drugs in Adult Horses. Animals (Basel) 2023 May 10;13(10).
- Salehi B, Rescigno A, Dettori T, Calina D, Docea AO, Singh L, Cebeci F, Özçelik B, Bhia M, Dowlati Beirami A, Sharifi-Rad J, Sharopov F, Cho WC, Martins N. Avocado-Soybean Unsaponifiables: A Panoply of Potentialities to Be Exploited. Biomolecules 2020 Jan 13;10(1).
- Attur M, Krasnokutsky S, Statnikov A, Samuels J, Li Z, Friese O, Hellio Le Graverand-Gastineau MP, Rybak L, Kraus VB, Jordan JM, Aliferis CF, Abramson SB. Low-grade inflammation in symptomatic knee osteoarthritis: prognostic value of inflammatory plasma lipids and peripheral blood leukocyte biomarkers. Arthritis Rheumatol 2015 Nov;67(11):2905-15.
- Labens R, Lascelles BD, Charlton AN, Ferrero NR, Van Wettere AJ, Xia XR, Blikslager AT. Ex vivo effect of gold nanoparticles on porcine synovial membrane. Tissue Barriers 2013 Apr 1;1(2):e24314.
- Freitas GC, Carregaro AB, Gehrcke MI, De La Côrte FD, Lara VM, Pozzobon R, Brass KE. Epidural analgesia with morphine or buprenorphine in ponies with lipopolysaccharide (LPS)-induced carpal synovitis. Can J Vet Res 2011 Apr;75(2):141-6.
- de Grauw JC, van de Lest CH, van Weeren PR. Inflammatory mediators and cartilage biomarkers in synovial fluid after a single inflammatory insult: a longitudinal experimental study. Arthritis Res Ther 2009;11(2):R35.
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