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Anatomia, histologia, embryologia2019; 49(5); 597-605; doi: 10.1111/ahe.12520

Endotoxin-induced changes in expression of cyclooxygenase isoforms in the lamellar tissue of extracorporeally haemoperfused equine limbs.

Abstract: Angiogenesis and sepsis-related equine laminitis have several features in common. Both events can be induced by endotoxin (lipopolysaccharide- LPS) and both are associated with increased expression of the enzyme cyclooxygenase (COX), of which two isoforms (COX-1 and COX-2) exist. To examine the causal relationship between LPS exposure and COX expression and to investigate the tissue distribution of COX in the LPS-exposed tissue, the technique of extracorporeal haemoperfusion of isolated equine forelimbs was utilized. Perfusion was performed for 10 hr under physiological conditions (control-perfused limbs, n = 5) and with addition of 80 ng/L of endotoxin (LPS-perfused limbs; n = 5). After perfusion, samples of lamellar tissue were collected from the dorsal aspect of the hoof wall. Additional control samples were collected from three non-perfused limbs. Immunohistochemical analysis was performed using antibodies against COX-1 and COX-2, and intensity of immunohistochemical staining was scored for each isoform. In the lamellar tissue of control- and LPS-perfused limbs, there was no significant difference in COX-1 staining intensity and distribution, whereas COX-2 expression was significantly increased in LPS-perfused limbs (especially in endothelial cells, fibroblasts and intravasal leucocytes as well as in epidermal basal cells at the base of the primary epidermal lamellae). These results suggest that COX-2 and its metabolites are involved in the initiation of pathological changes seen in sepsis-associated events such as sepsis-related laminitis. In such cases, COX-2 could therefore be an important therapeutic target; however, early therapy may be required as increase in COX-2 expression occurs within 10 hr after LPS exposure.
© 2019 The Authors. Anatomia, Histologia, Embryologia published by Wiley-VCH GmbH.
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Publication Date: 2019-11-27 PubMed ID: 31774594PubMed Central: PMC7540022DOI: 10.1111/ahe.12520Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research investigates the relationship between lipopolysaccharide (LPS) exposure and the expression of cyclooxygenase (COX) in horse foot tissues. The study uses a technique called extracorporeal haemoperfusion on isolated equine limbs, and it is found that exposure to LPS resulted in significantly increased expression of COX-2, suggesting that it might play a major role in conditions like sepsis-related laminitis.

Objective of the Study

  • The main objective of this study was to explore the relationship between exposure to endotoxin (specifically lipopolysaccharide or LPS) and the expression of cyclooxygenase (COX), an enzyme with two variants, COX-1 and COX-2, in the lamellar tissue of equine limbs. This relationship was particularly investigated in relation to conditions such as angiogenesis (new blood vessel formation) and sepsis-related laminitis, common illnesses in equines.

Methodology

  • The research team made use of extracorporeal haemoperfusion of isolated equine forelimbs. This is a technique where the blood flow to an isolated limb is controlled artificially, allowing researchers to precisely regulate the exposure to LPS.
  • Perfusion was performed for 10 hours under normal physiological conditions in some limbs (control group) and with the addition of 80 ng/L of endotoxin in another set of limbs (LPS-exposed group). Control samples were further collected from three non-perfused limbs.
  • An immunohistochemical analysis was performed on the collected lamellar tissue samples using antibodies against COX-1 and COX-2. The expression levels of COX-1 and COX-2 were then measured by evaluating the intensity of immunohistochemical staining for each isoform.

Findings

  • The analysis revealed no significant difference in COX-1 expression between the control and LPS-exposed limbs.
  • The COX-2 expression, on the other hand, was significantly higher in limbs perfused with LPS. Specifically, the increase in expression was observed in endothelial cells, fibroblasts, intravasal leukocytes, and epidermal basal cells at the base of the primary epidermal lamellae.

Implications

  • The findings suggest that COX-2 and its metabolites might be involved in initiating the pathological changes observed in sepsis-associated conditions like sepsis-related laminitis.
  • This also implies that COX-2 could be a potential therapeutic target in treating such conditions. However, since the increase in COX-2 expression occurs within 10 hours of LPS exposure, early intervention may be necessary for effective treatment.

Cite This Article

APA
Patan-Zugaj B, Egerbacher M, Licka TF. (2019). Endotoxin-induced changes in expression of cyclooxygenase isoforms in the lamellar tissue of extracorporeally haemoperfused equine limbs. Anat Histol Embryol, 49(5), 597-605. https://doi.org/10.1111/ahe.12520

Publication

Anatomia, histologia, embryologia
ISSN: 1439-0264
NlmUniqueID: 7704218
Country: Germany
Language: English
Volume: 49
Issue: 5
Pages: 597-605

Researcher Affiliations

Patan-Zugaj, Bianca
  • Institute of Topographic Anatomy, University of Veterinary Medicine Vienna, Vienna, Austria.
Egerbacher, Monika
  • Institute of Pathology, University of Veterinary Medicine Vienna, Vienna, Austria.
Licka, Theresia F
  • Equine University Clinic, University of Veterinary Medicine Vienna, Vienna, Austria.
  • Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, UK.

MeSH Terms

  • Animals
  • Extracorporeal Circulation / veterinary
  • Forelimb / blood supply
  • Forelimb / enzymology
  • Horses
  • Immunohistochemistry / veterinary
  • Lipopolysaccharides / pharmacology
  • Prostaglandin-Endoperoxide Synthases / classification
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Protein Isoforms
  • Random Allocation

Grant Funding

  • University of Veterinary Medicine Vienna
  • International Federation against Animal Experiments (Internationaler Bund der Tierversuchsgegner)

Conflict of Interest Statement

None of the authors has any financial or personal relationships that could inappropriately influence or bias the content of the paper.

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Citations

This article has been cited 2 times.
  1. Underberg BA, Van der Vekens E, Drews B, Kaessmeyer S. Cyclooxygenase-2 and von Willebrand factor-an immunohistochemical study of the equine foot with and without laminitis, post-mortem perfused with paraffin oil. Front Vet Sci 2025;12:1673415.
    doi: 10.3389/fvets.2025.1673415pubmed: 41473106google scholar: lookup
  2. Fikri F, Purnomo A, Maslamama ST, Purnama MTE. Effectiveness of acupuncture for equine laminitis: Systematic review and meta-analysis. Vet World 2025 Jan;18(1):60-66.
    doi: 10.14202/vetworld.2025.60-66pubmed: 40041523google scholar: lookup
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