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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Ezetimibe treatment significantly reduced endometriotic explant size in rats by decreasing TNF-α, VEGF, and mast cell expression.

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This study evaluated whether antilipidemic ezetimibe affects endometriotic lesion size and inflammatory/angiogenic markers in an experimental rat model of endometriosis. After surgically induced lesions were established, rats were randomized to receive oral ezetimibe (1 mg/kg/day) or saline for 28 days, with explant dimensions measured before and after treatment and tissues assessed histopathologically for TNF-α and VEGF expression and mast cell numbers. Ezetimibe significantly reduced endometriotic explant size versus controls and was associated with lower median TNF-α and VEGF levels and fewer mast cells across uterine layers; the authors note that post- versus pretreatment size differences were similar between groups. This paper is centrally about endometriosis — ezetimibe–induced regression of endometriotic explants in a rat model with 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. Similar content being viewed by others Data availability The data that support the findings of this study are available from the corresponding author (HA) upon request.

References

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Corresponding author Ethics declarations Ethics approval The study was approved by Mersin University’s local animal experiments ethics committee (approval number: 992903). Consent to participate This is an experimental animal study. Consent for publication This is an experimental animal study. Conflict of interest The authors declare no competing interests. Additional declarations for articles in life science journals that report the results of studies involving humans and/or animals All processes were carried out in accordance with the National Institute of Health “Guide for the care and Use of Laboratory Animals” rules. Additional information Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information Below is the link to the electronic supplementary material. Rights and permissions About this article Cite this article 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 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s00210-022-02226-2

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endometriosis

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Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Angiogenesis Inhibitors Angiogenesis Inhibitors Angiogenesis Inhibitors Angiogenesis Inhibitors Angiogenesis Inhibitors Angiogenesis Inhibitors Angiogenesis Inhibitors Angiogenesis Inhibitors Animals Animals Animals

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