Effects of oral administration of phenylbutazone to horses on in vitro articular cartilage metabolism.
Abstract: To evaluate the effects of orally administered phenylbutazone on proteoglycan synthesis and chondrocyte inhibition by IL-1beta in articular cartilage explants of horses. Methods: 11 healthy 1- to 2-year-old horses. Methods: Horses were randomly assigned to the control (n = 5) or treated group (4.4 mg of phenylbutazone/kg of body weight, p.o., q 12 h; n = 6). Articular cartilage specimens were collected before treatment was initiated (day 0), after 14 days of treatment, and 2 weeks after cessation of treatment (day 30). Proteoglycan synthesis and stromelysin concentration in cartilage extracts were assessed after 72 hours of culture in medium alone or with recombinant human interleukin-1beta (IL-1beta; 0.1 ng/ml). Results: On day 0, proteoglycan synthesis was significantly less in cartilage explants cultured in IL-1beta, compared with medium alone. Mean proteoglycan synthesis in explants collected on days 14 and 30 was significantly less in treated horses, compared with controls. However, incubation of explants from treated horses with IL-1beta did not result in a further decrease in proteoglycan synthesis. Significant differences in stromelysin concentration were not detected between or within groups. Conclusions: Oral administration of phenylbutazone for 14 days significantly decreased proteoglycan synthesis in articular culture explants from healthy horses to a degree similar to that induced by in vitro exposure to IL-1beta. Phenylbutazone should be used judiciously in athletic horses with osteoarthritis, because chronic administration may suppress proteoglycan synthesis and potentiate cartilage damage.
Publication Date: 2002-01-05 PubMed ID: 11763181DOI: 10.2460/ajvr.2001.62.1916Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research examines the effects of phenylbutazone, a medication given to horses, on the synthesis of proteoglycans – vital components for cartilage health – and how it impacts the response of articular cartilage cells to inflammation. The study suggests phenylbutazone decreases proteoglycan production and may exacerbate cartilage damage when administered chronically, thus necessitating careful use in horses with osteoarthritis.
Objective and Methodology
- The experiment aimed at investigating the influence of orally given phenylbutazone on the production of proteoglycans and the response of cartilage cells (chondrocytes) to inflammation provoked by interleukin-1beta (IL-1beta) in horse articular cartilage.
- The study involved 11 healthy horses which were divided into two groups: a control group and a treatment group receiving phenylbutazone (4.4 mg per kg of body weight) twice daily.
- Cartilage samples were obtained prior to the treatment (day 0), after two weeks (day 14), and two weeks post cessation of treatment (day 30). These samples were later cultured in two separate conditions – in a medium alone and in a medium along with an inflammatory agent, IL-1beta.
- The proteoglycans production and levels of matrix metalloproteinases (represented by stromelysin) were measured after 72 hours of cell culture.
Results
- When the cartilage cells were cultured in medium with IL-1beta, proteoglycan synthesis was significantly less than when cultured in medium only, showing the impact of inflammatory conditions on cartilage health.
- The horses that received phenylbutazone treatment displayed significantly lower synthesis of proteoglycans on both 14th and 30th days than controls did. Furthermore, combining phenylbutazone treatment with IL-1beta did not result in any further decrease in the proteoglycan synthesis.
- No substantial differences in the stromelysin concentration between or within groups were found, indicating the drug didn’t influence this crucial component to matrix degredation in osteoarthritis.
Conclusions
- The research concludes that phenylbutazone, when administered orally and continuously, significantly suppresses the creation of proteoglycans in the articular cartilage of horses – a factor that’s similarly induced by in vitro exposure to IL-1beta.
- The findings imply that continued use of this drug could potentially worsen the cartilage damage. As proteoglycans are essential for cartilage health, the suppression of its synthesis by phenylbutazone may exacerbate joint degradation in horses with osteoarthritis.
- The authors propose cautious use of phenylbutazone in athletic horses having osteoarthritis due to its adverse effects on cartilage metabolism.
Cite This Article
APA
Beluche LA, Bertone AL, Anderson DE, Rohde C.
(2002).
Effects of oral administration of phenylbutazone to horses on in vitro articular cartilage metabolism.
Am J Vet Res, 62(12), 1916-1921.
https://doi.org/10.2460/ajvr.2001.62.1916 Publication
Researcher Affiliations
- Department of Veterinary Clinical Sciences, The Ohio State University, Columbus 43210, USA.
MeSH Terms
- Administration, Oral
- Animals
- Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
- Anti-Inflammatory Agents, Non-Steroidal / pharmacology
- Cartilage, Articular / drug effects
- Cartilage, Articular / metabolism
- Horses / metabolism
- Interleukin-1 / pharmacology
- Matrix Metalloproteinase 3 / analysis
- Matrix Metalloproteinase 3 / biosynthesis
- Phenylbutazone / administration & dosage
- Phenylbutazone / pharmacology
- Proteoglycans / analysis
- Proteoglycans / biosynthesis
- Random Allocation
- Synovial Fluid / chemistry
Citations
This article has been cited 1 times.- O'Brien M, Mochel JP, Kersh K, Wang C, Troy J. Phenylbutazone concentrations in synovial fluid following administration via intravenous regional limb perfusion in the forelimbs of six adult horses.. Front Vet Sci 2023;10:1236976.
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