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However, the clinical use of DOX is limited due to its potential toxic effect on the cardiovascular system. Thus, identifying the pathway involved in this toxicity may help minimize chemotherapy risk and improve cancer patients\u2019 quality of life. Recent studies suggest that Endothelial-to-Mesenchymal transition (EndMT) and endothelial toxicity contribute to the pathogenesis of DOX-induced cardiovascular toxicity. However, the molecular mechanism is yet unknown. Given that arachidonic acid  and associated cytochrome P450 (CYP) epoxygenase have been involved in endothelial and cardiovascular function, we aimed to examine the effect of suppressing CYP epoxygenases on DOX-induced EndMT and cardiovascular toxicity in vitro and in vivo.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p>To test this, human endothelial cells were treated with DOX, with or without CYP epoxygenase inhibitor, MSPPOH. We also investigated the effect of MSPPOH on the cardiovascular system in our zebrafish model of DOX-induced cardiotoxicity. Our results showed that MSPPOH exacerbated DOX-induced EndMT, inflammation, oxidative stress, and apoptosis in our endothelial cells. Furthermore, we also show that MSPPOH increased cardiac edema, lowered vascular blood flow velocity, and worsened the expression of EndMT and cardiac injury markers in our zebrafish model of DOX-induced cardiotoxicity.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Our data indicate that a selective CYP epoxygenase inhibitor, MSPPOH, induces EndMT and endothelial toxicity to contribute to DOX-induced cardiovascular toxicity.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s11033-024-09803-z","type":"journal-article","created":{"date-parts":[[2024,7,27]],"date-time":"2024-07-27T14:01:36Z","timestamp":1722088896000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Inhibition of cytochrome P450 epoxygenase promotes endothelium-to-mesenchymal transition and exacerbates doxorubicin-induced cardiovascular toxicity"],"prefix":"10.1007","volume":"51","author":[{"given":"Hevna","family":"Dhulkifle","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lubna","family":"Therachiyil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maram H.","family":"Hasan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tahseen S.","family":"Sayed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahd M.","family":"Younis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hesham M.","family":"Korashy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huseyin C.","family":"Yalcin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaid H.","family":"Maayah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,27]]},"reference":[{"key":"9803_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2022.166352","volume":"1868","author":"IY Abdelgawad","year":"2022","unstructured":"Abdelgawad IY, Agostinucci K, Zordoky BN (2022) Cardiovascular ramifications of therapy-induced endothelial cell senescence in cancer survivors. 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All animal studies were conducted in accordance with international guidelines and the polices required by Qatar University and the Department of Research in the Ministry of Public Health for the use of zebrafish in experimental studies under the approval of the Institutional Animal Care and Use Committee (IACUC) (QU-IACUC 020\/2020-REN2).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"This study does not involve any clinical-related study and no patients were enrolled.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Research involving human participants"}}],"article-number":"859"}}