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Dose limiting toxicity on major organs, especially cardiovascular system limits the therapeutic use of 5-FU. The current paper addresses the cardioprotective effect of green synthesized selenium nanoparticles through kaempferol (KMP-SeNPs) on the cardiotoxicity induced by 5-FU in a rat model. 35 male Wistar rats were divided equally into five groups, namely control, 5-FU, Na\n                    <jats:sub>2<\/jats:sub>\n                    SeO\n                    <jats:sub>3<\/jats:sub>\n                    &amp;5-FU, KMP&amp;5-FU, and KMP-SeNPs&amp;5-FU. The 5-FU consumed 5 days induced cardiotoxicity and there were 21 days of oral treatment. The levels of cardiac injury markers, oxidative stress indices, antioxidant enzymes, inflammatory\/anti-inflammatory cytokines and apoptotic markers were measured by ELISA, gene expression and immunohistochemistry. The evaluation of cardiac tissue was done by using histopathology. 5-FU caused significant cardiotoxicity detected by increased cardiac enzymes, oxidative stress, inflammatory cytokines, apoptosis, and extensive histopathologic damage. KMP-SeNPs treatment had a great impact on reducing myocardial injury, normalizing cardiac enzymes, decreasing lipid peroxidation and NO generation, reestablishing antioxidant defenses, and increasing Nrf2 signaling and inhibiting Keap-1 expression. The expression of TNF-\u03b1, IL-6, NF-\u03baB, Bax, and caspase-3, were significantly decreased, whereas IL-10, FOXP3, and Bcl-2 showed a significant increase, which is evidence of the great anti-inflammatory, as well as anti-apoptotic effect of KMP-SeNPs. Immunohistochemical and histopathology results supported these molecular and biochemical findings to show approximately normal cardiac architecture. KMP-SeNPs are more effective in protecting against 5-FU-induced cardiotoxicity using antioxidant, anti-inflammatory, immunoregulatory, and anti-apoptotic activities.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-69038-9","type":"journal-article","created":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T09:44:13Z","timestamp":1789206253000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting mitochondrial dysfunction and apoptosis in 5-fluorouracil\u2013induced cardiotoxicity using kaempferol-mediated selenium nanoparticles"],"prefix":"10.1038","volume":"16","author":[{"given":"Sami Mohamed","family":"Nasr","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed Mahmoud","family":"Gad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahd Abdelsalam","family":"Taha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nouran H.","family":"Hindam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai Rabea","family":"Mohamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya G.","family":"Badawy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariam Mohamed","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moustafa Mahmoud","family":"Abdelaziz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled M.","family":"Alam-ElDein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1976-9480","authenticated-orcid":false,"given":"Mohamed H.A.","family":"Gadelmawla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,12]]},"reference":[{"key":"69038_CR1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/6194532","volume":"2022","author":"S Safarpour","year":"2022","unstructured":"Safarpour, S. et al. 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