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However, CP is associated with various adverse effects, one of which is cardiotoxicity. To minimize this toxicity, a common clinical strategy involves combining CP with a cytoprotective agent. One of the main causes of cardiac toxicity from CP is redox imbalance. Nebivolol, an antihypertensive medication that selectively targets \u03b2\n                    <jats:sub>1<\/jats:sub>\n                    \u2010adrenoceptors, has demonstrated cardioprotective effects in certain situations, partly due to its antioxidant properties. In this study, we evaluated whether nebivolol could reduce the harmful effects of CP on the heart. Male C57BL\/6 mice were treated with nebivolol (10\u2009mg\/kg\/day, administered by gavage for 5\u2009days) and subsequently injected with either saline or a single dose of CP (300\u2009mg\/kg, via intraperitoneal injection). We assessed pro\u2010oxidative and pro\u2010inflammatory parameters in the left ventricle 24\u2009h after the CP injection. Treatment with CP resulted in increased levels of superoxide (O\n                    <jats:sub>2<\/jats:sub>\n                    <jats:sup>\u2022\u2212<\/jats:sup>\n                    ) derived from NADPH\u2010oxidase, upregulation of NOX1 expression, and elevated hydrogen peroxide (H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    ) levels and lipoperoxidation. Pretreatment with nebivolol significantly mitigated these pro\u2010oxidative effects. Moreover, nebivolol prevented the increase in COX2 expression induced by CP. Echocardiographic analyses indicated that, despite the molecular changes caused by CP, cardiac function was preserved in the CP\u2010injected mice. In conclusion, nebivolol demonstrates cardioprotective effects against the toxicity of CP by reducing pro\u2010oxidative and pro\u2010inflammatory responses. Thus, nebivolol may represent a novel clinical approach for managing the cardiotoxic effects associated with CP.\n                  <\/jats:p>","DOI":"10.1111\/fcp.70047","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T14:21:05Z","timestamp":1757686865000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Nebivolol Mitigates the Pro\u2010Oxidative and Pro\u2010Inflammatory Effects of Cyclophosphamide in the Heart"],"prefix":"10.1111","volume":"39","author":[{"given":"Barbara\u00a0M.","family":"Marchetti","sequence":"first","affiliation":[{"name":"Faculdade de Ci\u00eancias Farmac\u00eauticas de Ribeir\u00e3o Preto, Universidade de S\u00e3o Paulo (USP) Laborat\u00f3rio de Farmacologia Cardiovascular, Departamento de Ci\u00eancias BioMoleculares  Ribeir\u00e3o Preto, S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thales\u00a0M.\u00a0H.","family":"Dourado","sequence":"additional","affiliation":[{"name":"Faculdade de Ci\u00eancias Farmac\u00eauticas de Ribeir\u00e3o Preto, Universidade de S\u00e3o Paulo (USP) Laborat\u00f3rio de Farmacologia Cardiovascular, Departamento de Ci\u00eancias BioMoleculares  Ribeir\u00e3o Preto, S\u00e3o Paulo Brazil"},{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Farmacologia Faculdade de Medicina de Ribeir\u00e3o Preto, USP  Ribeir\u00e3o Preto, S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gustavo\u00a0F.","family":"Pimenta","sequence":"additional","affiliation":[{"name":"Faculdade de Ci\u00eancias Farmac\u00eauticas de Ribeir\u00e3o Preto, Universidade de S\u00e3o Paulo (USP) Laborat\u00f3rio de Farmacologia Cardiovascular, Departamento de Ci\u00eancias BioMoleculares  Ribeir\u00e3o Preto, S\u00e3o Paulo Brazil"},{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Farmacologia Faculdade de Medicina de Ribeir\u00e3o Preto, USP  Ribeir\u00e3o Preto, S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra\u00a0O.","family":"Silva","sequence":"additional","affiliation":[{"name":"Faculdade de Ci\u00eancias Farmac\u00eauticas de Ribeir\u00e3o Preto, Universidade de S\u00e3o Paulo (USP) Laborat\u00f3rio de Farmacologia Cardiovascular, Departamento de Ci\u00eancias BioMoleculares  Ribeir\u00e3o Preto, S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9779-733X","authenticated-orcid":false,"given":"Carlos\u00a0R.","family":"Tirapelli","sequence":"additional","affiliation":[{"name":"Departamento de Ci\u00eancias BioMoleculares Universidade de S\u00e3o Paulo, Faculdade de Ci\u00eancias Farmac\u00eauticas de Ribeir\u00e3o Preto  Ribeir\u00e3o Preto SP 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