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International journal of molecular sciences2023; 24(4); 3593; doi: 10.3390/ijms24043593

Inhibition of Myeloperoxidase Pro-Fibrotic Effect by Noscapine in Equine Endometrium.

Abstract: Myeloperoxidase is an enzyme released by neutrophils when neutrophil extracellular traps (NETs) are formed. Besides myeloperoxidase activity against pathogens, it was also linked to many diseases, including inflammatory and fibrotic ones. Endometrosis is a fibrotic disease of the mare endometrium, with a large impact on their fertility, where myeloperoxidase was shown to induce fibrosis. Noscapine is an alkaloid with a low toxicity, that has been studied as an anti-cancer drug, and more recently as an anti-fibrotic molecule. This work aims to evaluate noscapine inhibition of collagen type 1 (COL1) induced by myeloperoxidase in equine endometrial explants from follicular and mid-luteal phases, at 24 and 48 h of treatment. The transcription of collagen type 1 alpha 2 chain (), and COL1 protein relative abundance were evaluated by qPCR and Western blot, respectively. The treatment with myeloperoxidase increased mRNA transcription and COL1 protein, whereas noscapine was able to reduce this effect with respect to mRNA transcription, in a time/estrous cycle phase-dependent manner (in explants from the follicular phase, at 24 h of treatment). Our study indicates that noscapine is a promising drug to be considered as an anti-fibrotic molecule to prevent endometrosis development, making noscapine a strong candidate to be applied in future endometrosis therapies.
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Publication Date: 2023-02-10 PubMed ID: 36835008PubMed Central: PMC9959736DOI: 10.3390/ijms24043593Google 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 use of noscapine, an alkaloid, to inhibit myeloperoxidase-induced fibrosis in the equine endometrium. The study proposes that noscapine could be a potential treatment for endometrosis, a fibrotic condition affecting fertility in mares.

Background

  • The study is based on the role of myeloperoxidase (MPO), an enzyme released by neutrophils in response to pathogens. While generally beneficial for neutralizing infections, MPO has also been associated with various inflammatory and fibrotic diseases.
  • One such fibrotic disease is endometrosis, a condition that affects the endometrium in mares and has significant effects on their fertility.

Methodology

  • To test the potential of noscapine as an anti-fibrotic treatment, the researchers used equine endometrial explants from both the follicular and the mid-luteal phases, and examined them at 24 and 48 hours after treatment.
  • They specifically studied the effects of MPO and noscapine on the transcription of collagen type 1 alpha 2 chain () and collagen type 1 (COL1) protein.
  • The mRNA transcription and relative abundance of COL1 protein were analyzed using qPCR and Western blot techniques respectively.

Findings

  • The researchers found that MPO increased the transcription of mRNA and COL1 protein, which are both implicated in fibrotic conditions.
  • Conversely, noscapine effectively reduced the induced transcription of the mRNA in a time and estrous cycle phase-dependent manner, showing most efficacy in the follicular phase at 24 hours of treatment.

Conclusion

  • The outcomes of the study suggest that noscapine has the potential to be an effective anti-fibrotic drug, offering a promising path to prevent the development of endometrosis.
  • However, its optimum use will be determined by the specific timing in relation to the estrous cycle and the duration of treatment required to effectively reduce mRNA transcription and COL1 protein.

Cite This Article

APA
Amaral A, Cebola N, Szóstek-Mioduchowska A, Rebordão MR, Kordowitzki P, Skarzynski D, Ferreira-Dias G. (2023). Inhibition of Myeloperoxidase Pro-Fibrotic Effect by Noscapine in Equine Endometrium. Int J Mol Sci, 24(4), 3593. https://doi.org/10.3390/ijms24043593

Publication

International journal of molecular sciences
ISSN: 1422-0067
NlmUniqueID: 101092791
Country: Switzerland
Language: English
Volume: 24
Issue: 4
PII: 3593

Researcher Affiliations

Amaral, Ana
  • CIISA-Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, 1300-477 Lisbon, Portugal.
  • Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisbon, Portugal.
  • Department of Zootechnics, School of Sciences and Technology (ECT), University of Évora, 7002-554 Évora, Portugal.
  • Comprehensive Health Research Centre (CHRC), 7000-811 Évora, Portugal.
Cebola, Nélio
  • Faculty of Veterinary Medicine, Universidade Lusofona, 1749-024 Lisbon, Portugal.
  • Veterinary Teaching Hospital of the University of Extremadura, 10003 Cáceres, Spain.
Szóstek-Mioduchowska, Anna
  • Institute of Animal Reproduction and Food Research, Polish Academy of Science, 10-748 Olsztyn, Poland.
Rebordão, Maria Rosa
  • CIISA-Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, 1300-477 Lisbon, Portugal.
  • Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisbon, Portugal.
  • Polytechnic of Coimbra, Coimbra Agriculture School, Bencanta, 3045-601 Coimbra, Portugal.
Kordowitzki, Paweł
  • Department of Basic and Preclinical Sciences, Institute for Veterinary Medicine, Nicolaus Copernicus University, ul. Gagarina 1, 87-100 Torun, Poland.
Skarzynski, Dariusz
  • Institute of Animal Reproduction and Food Research, Polish Academy of Science, 10-748 Olsztyn, Poland.
Ferreira-Dias, Graça
  • CIISA-Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, 1300-477 Lisbon, Portugal.
  • Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisbon, Portugal.

MeSH Terms

  • Animals
  • Female
  • Collagen / metabolism
  • Endometrium / drug effects
  • Endometrium / metabolism
  • Fibrosis / drug therapy
  • Fibrosis / metabolism
  • Fibrosis / veterinary
  • Horses / metabolism
  • Noscapine / pharmacology
  • Noscapine / therapeutic use
  • Peroxidase / antagonists & inhibitors
  • Peroxidase / metabolism
  • RNA, Messenger / metabolism

Grant Funding

  • UIDB/00276/2020; LA/P/0059/2020 / Fundau00e7u00e3o para a Ciu00eancia e Tecnologia
  • PTDC/CVT-REP/4202/2014 / Fundau00e7u00e3o para a Ciu00eancia e Tecnologia
  • SFRH/BD/101058/2014 / Fundau00e7u00e3o para a Ciu00eancia e Tecnologia
  • PPN/BIL/2018/1/00250/U/0001 / Narodowa Agencja Wymiany Akademickiej (NAWA)

Conflict of Interest Statement

The authors declare no conflict of interest.

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Citations

This article has been cited 1 times.
  1. Ferreira-Dias GM, Alpoim-Moreira J, Szóstek-Mioduchowska A, Rebordão MR, Skarzynski DJ. The path to fertility: Current approaches to mare endometritis and endometrosis. Anim Reprod 2024;21(3):e20240070.
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