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Nevertheless, it causes damage to the heart by activating inflammatory pathways, resulting in cardiotoxicity. Imbalance in cytokine production is a crucial component that might trigger the initiation of inflammatory processes. Inflammatory cytokines could be targeted therapies against cardiovascular diseases (CVDs). Interleukin-17A (IL-17A) is a cytokine that promotes inflammation and stimulates harmful immunological reactions. The objective of the study was to determine the efficacy of secukinumab (SEC), a completely human monoclonal IgG1\/\u03ba antibody that targets IL-17A, in ameliorating DOX-induced cardiotoxicity (DIC). We administered 2.5 mg\/kg of DOX intraperitoneally to male Wistar rats three times a week for 2 weeks and simultaneously administered 0.9 mg\/kg of SEC along with 2.5 mg\/kg of DOX injection three times a week for a duration of two weeks. The findings indicated that DOX induced damage to the heart tissue, resulting in a significant rise in indicators of cardiotoxicity (P\u2009&lt;\u20090.001), as well as oxidative stress and inflammation. DIC may have arisen from DOX's activation of the Pyrin domain containing 3 (NLRP3) inflammasome and the nuclear factor kappa beta (NF-\u03baB) pathway. The co-administration of SEC successfully reversed all DOX-induced abnormalities by restoring cardiac functions to their baseline levels, decreasing levels of inflammatory mediators such as IL-17A and interleukin-1\u03b2 (IL-1\u03b2), and improving oxidative stress by reducing levels of malondialdehyde (MDA) and increasing levels of reduced glutathione (GSH). Furthermore, it mitigated the heightened activation of the NF-\u03baB\/NLRP3 pathway caused by DOX. This study shows that IL-17A neutralization can prevent DIC by regulating the NF-\u03baB\/NLRP3\/Caspase-1\/IL-1\u03b2 pathway to be used as potential therapeutic target for CVDs.<\/jats:p>","DOI":"10.1007\/s10753-024-02187-z","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T19:47:26Z","timestamp":1741636046000},"page":"2244-2257","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["\u201cThe Ameliorative Effect of Interleukin-17A Neutralization on Doxorubicin-Induced Cardiotoxicity by Modulating the NF-\u03baB\/NLRP3\/Caspase-1\/IL-1\u03b2 Signaling Pathway in Rats\u201d"],"prefix":"10.1007","volume":"48","author":[{"given":"Mostafa D.","family":"Hassen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahla O.","family":"Mousa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara M.","family":"Radwan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7511-9204","authenticated-orcid":false,"given":"Refaat M.","family":"Gabre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,11]]},"reference":[{"key":"2187_CR1","doi-asserted-by":"publisher","unstructured":"Haupt, L. 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Pharmacology & Therapeutics 236: 108053. https:\/\/doi.org\/10.1016\/j.pharmthera.2021.108053.","DOI":"10.1016\/j.pharmthera.2021.108053"}],"container-title":["Inflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10753-024-02187-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10753-024-02187-z\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10753-024-02187-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T02:21:20Z","timestamp":1754878880000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10753-024-02187-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,11]]},"references-count":46,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["2187"],"URL":"https:\/\/doi.org\/10.1007\/s10753-024-02187-z","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-4314388\/v1","asserted-by":"object"}]},"ISSN":["1573-2576"],"issn-type":[{"value":"1573-2576","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,11]]},"assertion":[{"value":"8 August 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 September 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 November 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 March 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 July 2025","order":5,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":6,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This article has been updated to amend the license information.","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors do not have any significant competing interests to disclose about the content of this study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}},{"value":"The study received approval from the ethical committee of Cairo University, and all experimental procedures were licensed by the Animal Care and Use (CU-IACUC) Committee of Cairo University. We meticulously adhered to established protocols (Protocol # CU-I\/F\/15\/23) and rigorously followed NIH guidelines for animal research to ensure both the well-being of the animals and the accuracy of our experimental approaches.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}}]}}