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Effects of cyclooxygenase inhibitors flunixin and deracoxib on permeability of ischaemic-injured equine jejunum.
Abstract: Recent studies have shown that flunixin prevented recovery of equine jejunum post ischaemia. However, the use of a purported cyclooxygenase (COX)-2 preferential inhibitor, etodolac, also prevented recovery. These findings may have implications for the use of nonsteroidal anti-inflammatory drugs in colic patients. Objective: To compare the effects of deracoxib, a highly selective canine COX-2 inhibitor, with flunixin on in vitro recovery of ischaemic-injured equine jejunum. Methods: Six horses underwent 2 h jejunal ischaemia, after which mucosa was mounted in Ussing chambers and recovered for 240 mins. Transepithelial electrical resistance (TER) and mucosal-to-serosal fluxes of 3H-mannitol were monitored as indices of barrier function in the presence of flunixin or deracoxib. Results: The TER of ischaemic-injured tissue recovered significantly over 240 mins in the presence of no treatment, but not in the presence of flunixin or deracoxib. In addition, flunixin-treated ischaemic jejunum was significantly more permeable to mannitol when compared with untreated tissue by the end of the recovery period, whereas deracoxib treatment did not increase permeability. Addition of the PGE1 analogue misoprostol to flunixin-treated tissue restored recovery of TER. Conclusions: Treatment of horses with ischaemic jejunal disease with flunixin may result in a prolonged permeability defect in recovering mucosa. Addition of misoprostol or replacement of flunixin with deracoxib may ameliorate effects of COX inhibitors on recovering mucosa.
Publication Date: 2005-01-18 PubMed ID: 15651739DOI: 10.2746/0425164054406865Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
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This research article investigates the effects of two specific anti-inflammatory drugs, flunixin and deracoxib, on the recovery of intestinal injury in horses. The study finds that while both drugs hinder the recovery of the equine intestines after injury, addition of another drug, misoprostol, or switching flunixin with deracoxib, might mitigate these adverse effects.
Objective and Methodology
The main objective of the research was to compare the impacts of deracoxib, a dog-specific cyclooxygenase-2 (COX-2) inhibitor, and flunixin, on the recovery of ischemic-injured horse intestines. The test involved six horses which were subjected to intestinal ischemia (insufficient blood flow) for 2 hours. Afterwards, the mucosa (inner lining of the intestines) was located in Ussing chambers and allowed to recover for 240 minutes. Overall condition of the intestine’s barrier functionality was monitored and tracked using mannitol as an indicator.
- Transepithelial electrical resistance (TER) and mucosal-to-serosal fluxes of 3H-mannitol were used as markers for barrier function.
- Additionally, the PGE1 analogue misoprostol was added to flunixin-treated tissue to observe its recovery effect on TER.
Research Findings
The injured tissues showed significant recovery over 240 minutes without treatment, but not in the presence of either drug. Specifically:
- Flunixin-treated intestines were significantly more permeable to mannitol when compared with untreated tissues by the end of the recovery period.
- However, deracoxib treatment did not increase permeability.
- When misoprostol was added to flunixin-treated tissues, it aided in TER recovery.
Conclusions
Given the findings, treating horses with ischemic intestines with flunixin might result in prolonged permeability defect in the recuperating mucosa. This can disrupt the normal functions of a horse’s intestines after recovery from ischemia. On the other hand, replacing flunixin with deracoxib or introducing misoprostol could help reduce the adverse impacts of COX inhibitors on the healing mucosa. This research provides new avenues for managing post-ischemia recoveries in horses, showing possible pathways to mitigate the negative impact of essential anti-inflammatory drugs.
Cite This Article
APA
Tomlinson JE, Blikslager AT.
(2005).
Effects of cyclooxygenase inhibitors flunixin and deracoxib on permeability of ischaemic-injured equine jejunum.
Equine Vet J, 37(1), 75-80.
https://doi.org/10.2746/0425164054406865 Publication
Researcher Affiliations
- Department of Clinical Sciences, North Carolina State University, College of Veterinary Medicine, Raleigh, North Carolina 27606, USA.
MeSH Terms
- Animals
- Anti-Inflammatory Agents, Non-Steroidal / pharmacology
- Biological Transport
- Clonixin / analogs & derivatives
- Clonixin / pharmacology
- Cyclooxygenase 2
- Cyclooxygenase 2 Inhibitors
- Cyclooxygenase Inhibitors / pharmacology
- Electric Impedance
- Histological Techniques
- Horse Diseases / drug therapy
- Horses
- Intestinal Mucosa / blood supply
- Intestinal Mucosa / drug effects
- Ischemia / drug therapy
- Ischemia / veterinary
- Jejunum / blood supply
- Jejunum / drug effects
- Jejunum / metabolism
- Mannitol / metabolism
- Misoprostol / pharmacology
- Permeability / drug effects
- Prostaglandin-Endoperoxide Synthases / metabolism
- Prostaglandins / metabolism
- Reperfusion / veterinary
- Sulfonamides / pharmacology
- Tritium
Citations
This article has been cited 10 times.- Flood J, Stewart AJ. Non-Steroidal Anti-Inflammatory Drugs and Associated Toxicities in Horses. Animals (Basel) 2022 Oct 26;12(21).
- Ziegler AL, Blikslager AT. Sparing the gut: COX-2 inhibitors herald a new era for treatment of horses with surgical colic. Equine Vet Educ 2020 Nov;32(11):611-616.
- Ziegler AL, Fogle CA, Burke M, Blikslager AT. Letter to the Editor: Bias in statistics or bias in equine veterinary medicine?. Equine Vet J 2019 May;51(3):423.
- Martin EM, Schirmer JM, Jones SL, Davis JL. Pharmacokinetics and ex vivo anti-inflammatory effects of oral misoprostol in horses. Equine Vet J 2019 May;51(3):415-421.
- Blikslager A, Gonzalez L. Equine Intestinal Mucosal Pathobiology. Annu Rev Anim Biosci 2018 Feb 15;6:157-175.
- Martin EM, Messenger KM, Sheats MK, Jones SL. Misoprostol Inhibits Lipopolysaccharide-Induced Pro-inflammatory Cytokine Production by Equine Leukocytes. Front Vet Sci 2017;4:160.
- Martin EM, Till RL, Sheats MK, Jones SL. Misoprostol Inhibits Equine Neutrophil Adhesion, Migration, and Respiratory Burst in an In Vitro Model of Inflammation. Front Vet Sci 2017;4:159.
- 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.
- Urayama S, Muko R, Muranaka M, Mita H, Ohta M, Matsuda H, Tanaka A. Differential effects of flunixin meglumine and meloxicam on TNF- α production in LPS-stimulated equine neutrophils in vitro. Vet Anim Sci 2025 Dec;30:100513.
- Araújo RA, Sales NAA, Basile RC, Feringer-Junior WH, Apparício M, Ferraz GC, Queiroz-Neto A. Safety Assessment of an Oral Therapeutic Dose of Firocoxib on Healthy Horses. Vet Sci 2023 Aug 22;10(9).
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