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Antilipidemic ezetimibe induces regression of endometriotic explants in a rat model of endometriosis with its anti-inflammatory and anti-angiogenic effects

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Abstract

To assess the potential therapeutic role of antilipidemic ezetimibe on endometriosis in an experimental rat model. A standard experimental endometriosis model was created with 18 Whistar-Albino rats, and after 1 month, the sizes of the endometriotic explants were measured. The rats were randomized as study and control groups. A total of 1 mg/kg/day ezetimibe and 1 ml/kg/day saline were administered orally to the study and control groups respectively for 28 days. At the end of 28 days, the explants were measured again, excised, and sent for histopathologic assessment for expression of tumor necrosis factor-alpha (TNF-α) and vascular endothelial growth factor (VEGF) and number of mast cells. At the end of the study period, the size of the endometriotic explants decreased significantly in the study group; but not in the control group (from 145.3 ± 120.5 to 89.8 ± 60.1 vs 174.72 ± 88.3 to 87.65 ± 27.1 cm3 respectively); however, the amount of post- and pretreatment differences in explant sizes was similar in the groups. The median TNF-α and VEGF levels were significantly lower in the ezetimibe group when compared to the control group (4 [3–4] vs 2 [1–3], p 0.029; 4 [3–4] vs 2 [2–3], p 0.002; respectively). And numbers of mast cells in all uterine layers were also lower in the ezetimibe group. Ezetimibe decreased the size of the endometriotic explants with its anti-inflammatory and anti-angiogenic properties. This agent alone or with combination of other agents may have a potential role in the treatment of endometriosis.

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Data availability

The data that support the findings of this study are available from the corresponding author (HA) upon request.

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Funding

This work was supported by Mersin University Department of Scientific Research Projects (grant number: 2019–3-TP3-3810).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Faculty of Medicine, Mersin University, Mersin, Turkey

    Raziyya Tapdıgova & Hakan Aytan

  2. Department of Histology and Embryology, Faculty of Medicine, Mersin University, Mersin, Turkey

    Gülsen Bayrak & Banu Coşkun Yılmaz

Authors
  1. Raziyya Tapdıgova
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  2. Gülsen Bayrak
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  3. Banu Coşkun Yılmaz
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  4. Hakan Aytan
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Contributions

R. Tapdıgova: project development, data collection, assessment of the explants, manuscript writing.

G. Bayrak: ımmunohistochemical assessment.

B. Coşkun Yılmaz: ımmunohistochemical assessment.

H. Aytan: project development, data collection, surgical induction of endometriosis, statistical analysis, manuscript writing, editing.

The authors declare that all data were generated in-house and that no paper mill was used.

Corresponding author

Correspondence to Hakan Aytan.

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Ethics approval

The study was approved by Mersin University’s local animal experiments ethics committee (approval number: 992903).

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This is an experimental animal study.

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This is an experimental animal study.

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The authors declare no competing interests.

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All processes were carried out in accordance with the National Institute of Health “Guide for the care and Use of Laboratory Animals” rules.

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Tapdıgova, R., Bayrak, G., Yılmaz, B.C. et al. Antilipidemic ezetimibe induces regression of endometriotic explants in a rat model of endometriosis with its anti-inflammatory and anti-angiogenic effects. Naunyn-Schmiedeberg's Arch Pharmacol 395, 673–680 (2022). https://doi.org/10.1007/s00210-022-02226-2

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  • DOI: https://doi.org/10.1007/s00210-022-02226-2

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