{"paper_id":"8c412110-6193-4ee5-896c-cff3ee0b29f9","body_text":"Abstract\nThe study aimed to investigate the roles of endothelin-1 and endothelin receptors in a rat endometriosis model and to demonstrate how bosentan (BOS), an endothelin receptor blocker, could potentially serve as a novel treatment for endometriosis. Overall, 36 rats were divided into groups as follows: Group 1: Sham, Group 2: endometriosis, Group 3: Sham + BOS100 mg/kg, Group 4: endometriosis + BOS 25 mg/kg, Group 5: endometriosis + BOS 50 mg/kg, and Group 6: endometriosis + BOS 100 mg/kg. In the first laparotomy, an experimental endometriosis model was created by implanting a 0.5 × 0.5 cm2 piece of autologous endometrial tissue in Groups 2, 4, 5, and 6. After waiting for 4 weeks, a second laparotomy was performed to measure the endometriotic lesions in Groups 2, 4, 5, and 6. Following the measurements, Groups 4, 5, and 6 received oral administration of BOS at doses of 25 mg/kg, 50 mg/kg, and 100 mg/kg, respectively, for 2 weeks. Three groups received 100 mg/kg of BOS during the same time period. After the drug administration, a third laparotomy was performed, and the endometriotic lesions in Groups 2, 4, 5, and 6 were re-measured. Histopathological, immunohistochemical, biochemical, and molecular analyses of endometriotic lesion samples obtained after the experiment revealed a significant increase in the levels of TNF-α, TGF-β, MMP-9, ET-1, eNOS, VEGF, ETR-A, ETR-B, and MAPkinase in the experimental endometriosis group (Group 2). Conversely, these levels were significantly reduced in the BOS treatment groups (Groups 4, 5, and 6) in a dose-dependent manner compared to Group 2. Similarly, surface area measurements of endometriotic lesions showed a dose-dependent reduction in the BOS-treated groups (Groups 4, 5, and 6). The roles of endothelin-1 and its receptors in the pathophysiology and treatment of the endometriosis model of rats were demonstrated histopathologically, immunohistochemically, biochemically, and molecularly using BOS. This study can shed light on clinical treatment protocols for women with endometriosis.\nGraphical Abstract\nPossible effect mechanism of bosentan during endometriosis\nSimilar content being viewed by others\nData availability\nThe data that support the findings of this study are available from the corresponding author, ZH, upon reasonable request.\nReferences\nAnggrahini DW, Emoto N, Nakayama K et al (2009) Vascular endothelial cell-derived endothelin-1 mediates vascular inflammation and neointima formation following blood flow cessation. Cardiovasc Res 82:143–151. https://doi.org/10.1093/cvr/cvp026\nAugoulea A, Alexandrou A, Creatsa M et al (2012) Pathogenesis of endometriosis: the role of genetics, inflammation and oxidative stress. 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This study was supported by the Atatürk University Scientific Research Projects Coordination Unit with project number TDK-2023-12249, for which the authors express their sincere gratitude.\nFunding\nThis study was supported by the Atatürk University Scientific Research Projects Coordination Unit (grant number TDK-2023–12249).\nAuthor information\nAuthors and Affiliations\nContributions\nSSK and ZH conceived and designed research. SSK and ZH performed animal experiments and analysed the results. SSK and ZH wrote the manuscript. EC contributed to conceptualisation, writing and statistical analyses of data. ET performed all histopathological examinations. All authors read and approved the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.\nCorresponding author\nEthics declarations\nEthics approval and consent to participate\nApproval was obtained for animal studies with the letter dated 26–09-2022 and numbered E-42190979–000-2200292976 from Atatürk University Animal Experiments Local Ethics Committee.\nConsent for publication\nAll participants provided written informed consent for publication.\nCompeting interests\nThe authors declare no competing interests.\nAdditional information\nPublisher's Note\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\nRights and permissions\nSpringer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.\nAbout this article\nCite this article\nKarcioglu, S.S., Halici, Z., Cadirci, E. et al. Investigation of endothelin-1 receptor antagonist bosentan in a rat endometriosis model. Naunyn-Schmiedeberg's Arch Pharmacol 399, 8821–8835 (2026). https://doi.org/10.1007/s00210-025-04935-w\nReceived:\nAccepted:\nPublished:\nVersion of record:\nIssue date:\nDOI: https://doi.org/10.1007/s00210-025-04935-w","source_license":"public-domain-us","license_restricted":false}