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Home / Equine Research Bank / Front Vet Sci / Tamoxifen triggers the in vitro release of neutrophil extrac...
Frontiers in veterinary science2023; 9; 1025249; doi: 10.3389/fvets.2022.1025249

Tamoxifen triggers the in vitro release of neutrophil extracellular traps in healthy horses.

Abstract: Neutrophils display an array of biological functions including the formation of neutrophil extracellular traps (NETs), web-like structures specialized in trapping, neutralizing, killing and preventing microbial dissemination within the host. However, NETs contribute to a number of inflammatory pathologies, including severe equine asthma. Tamoxifen (TX) is a selective estrogen receptor modulator which belongs to the triphenylethyllenes group of molecules, and which is used as a treatment in all stages of estrogen-positive human breast cancer. Our previous results suggest that tamoxifen can modulate neutrophil functionality and promote resolution of inflammation; this would partly explain the clinical beneficial effect of this drug in horses with airway inflammation. Enhanced NETs production has been reported with tamoxifen use in humans, but minimal data exists regarding the drug's effect on NETs in horses. The aim of this study is to assess the effect of TX on NETs formation from peripheral blood of healthy horses. Five clinically healthy mixed-breed adult horses were enrolled in the study. For this, cellular free DNA quantification, immunofluorescence for the visualization of NETs, assessment of different types of NETs, and detection of mitochondrial superoxide. TX induced NETs formation at a concentration of 10 uM. Our results show that only two types of NETs were induced by TX: 95% spread NETs () and 5% aggregated NETs (). Furthermore, induction of these NETs could be influenced by mitochondrial ROS. Future research should involve an study of horses with severe asthma and TX treatment, to evaluate BALF neutrophil NET formation. In conclusion, this study suggests that the resolution of inflammation by TX in horses with airway inflammation is due to inhibition of other neutrophilic functions but not to NET formation.
Copyright © 2023 Salinas, Barriga, Albornoz, Alarcon, Quiroga, Uberti, Sarmiento, Henriquez, Ehrenfeld, Burgos and Moran.
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Publication Date: 2023-01-06 PubMed ID: 36686170PubMed Central: PMC9853556DOI: 10.3389/fvets.2022.1025249Google 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.

The research article focuses on the ability of tamoxifen, a drug used in treating human breast cancer, to trigger the release of neutrophil extracellular traps (NETs) in healthy horses.

Summary and Purpose of the Research

  • Neutrophils are cells in the body which have numerous biological functions, including forming NETs – web-like structures that trap and neutralize microbes, preventing their spread within the host.
  • However, NETs have been linked with numerous inflammatory diseases, including severe equine asthma. This is where the interest in tamoxifen comes in.
  • Tamoxifen is a drug that modulates estrogen receptors, and it’s often used in the treatment of all stages of estrogen-positive human breast cancer.
  • Prior research has suggested that tamoxifen can influence the functionality of neutrophils and help resolve inflammation. This has led to its use in treating airway inflammation in horses.
  • While tamoxifen has been linked with increased NET production in humans, this effect is not well-studied in horses. The researchers thus aim to understand how tamoxifen influences NET formation in horses.

Methodology

  • The study involved five healthy adult horses of mixed breed.
  • Different tests were run, including quantifying cell-free DNA, using immunofluorescence to visualize NETs, and identification of different types of NETs.
  • A key point of analysis was the mitochondrial superoxide, a reactive oxygen species (ROS) that plays a role in the production of NETs.

Findings

  • The study found that tamoxifen can trigger the formation of NETs at a concentration of 10 micromolar (uM).
  • Importantly, tamoxifen specifically induced the formation of two types of NETs: 95% spread NETs and 5% aggregated NETs.
  • Further, the formation of these NETs appeared to be influenced by mitochondrial ROS.
  • In conclusion, the study uncovered insights suggesting tamoxifen’s role in resolving inflammation in horses with airway problems is not linked to the formation of NETs but due to the drug’s influence on other neutrophil functionalities.

Implications and Future Directions

  • The study provides a basis for understanding the effects of tamoxifen on neutrophils and NETs formation in horses.
  • The authors suggest that future research should investigate the effect of tamoxifen on NET formation in horses suffering from severe asthma.

Cite This Article

APA
Salinas C, Barriga K, Albornoz A, Alarcon P, Quiroga J, Uberti B, Sarmiento J, Henriquez C, Ehrenfeld P, Burgos RA, Moran G. (2023). Tamoxifen triggers the in vitro release of neutrophil extracellular traps in healthy horses. Front Vet Sci, 9, 1025249. https://doi.org/10.3389/fvets.2022.1025249

Publication

Frontiers in veterinary science
ISSN: 2297-1769
NlmUniqueID: 101666658
Country: Switzerland
Language: English
Volume: 9
Pages: 1025249
PII: 1025249

Researcher Affiliations

Salinas, Constanza
  • Instituto de Farmacología y Morfofisiología, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Valdivia, Chile.
Barriga, Kassandra
  • Instituto de Farmacología y Morfofisiología, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Valdivia, Chile.
Albornoz, Alejandro
  • Instituto de Farmacología y Morfofisiología, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Valdivia, Chile.
Alarcon, Pablo
  • Instituto de Farmacología y Morfofisiología, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Valdivia, Chile.
Quiroga, John
  • Instituto de Farmacología y Morfofisiología, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Valdivia, Chile.
Uberti, Benjamín
  • Instituto de Ciencias Clínicas Veterinarias, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Valdivia, Chile.
Sarmiento, José
  • Instituto de Fisiología, Facultad de Medicina, Universidad Austral de Chile, Valdivia, Chile.
Henriquez, Claudio
  • Instituto de Farmacología y Morfofisiología, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Valdivia, Chile.
Ehrenfeld, Pamela
  • Instituto de Anatomía, Histología y Patología, Facultad de Medicina, Universidad Austral de Chile, Valdivia, Chile.
Burgos, Rafael A
  • Instituto de Farmacología y Morfofisiología, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Valdivia, Chile.
Moran, Gabriel
  • Instituto de Farmacología y Morfofisiología, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Valdivia, Chile.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Citations

This article has been cited 2 times.
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  2. Birckhead EM, Das S, Tidd N, Raidal SL, Raidal SR. Visualizing neutrophil extracellular traps in septic equine synovial and peritoneal fluid samples using immunofluorescence microscopy. J Vet Diagn Invest 2023 Nov;35(6):751-760.
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