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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Cisplatin is an effective chemotherapeutic agent whose clinical use is limited by dose-dependent off-target toxicities, particularly hepatic and cardiac injury. The present study investigated the protective efficacy of rutin-mediated selenium nanoparticles (RUT-SeNPs) against cisplatin-induced hepato-cardiotoxicity in rats and compared their effects against those of free rutin and sodium selenite. RUT-SeNPs were characterized using dynamic light scattering, zeta potential analysis, transmission electron microscopy, X-ray diffraction, and UV\u2013visible spectroscopy. Thirty-five male rats were randomly assigned to five groups: control (CON), cisplatin (CIS), CIS + Rutin, CIS + selenium, and CIS + RUT-SeNPs. Cisplatin administration caused marked hepatic and cardiac injury, as evidenced by altered liver-function indices, elevated cardiac injury biomarkers, oxidative stress, inflammatory activation, endoplasmic reticulum stress, and apoptosis. These effects were associated with increased lipid peroxidation, depletion of endogenous antioxidants, KEAP1 upregulation, Nrf2 suppression, activation of the TLR4\/MAPK\/NF-\u03baB inflammatory axis, elevated TNF-\u03b1, IL-6, and COX-2 levels, and increased mRNA expression of the ER stress-related genes PERK, ATF4, ATF6, and CHOP. Cisplatin also promoted mitochondrial apoptosis, as indicated by increased Bax expression and cytochrome c release together with reduced Bcl-2 levels. Although rutin and sodium selenite partially mitigated these alterations, RUT-SeNPs produced the most pronounced protective effects by restoring redox homeostasis, suppressing inflammatory signaling, reducing the elevated expression of ER stress-related genes, and limiting mitochondrial apoptotic activation. These molecular improvements were accompanied by substantial preservation of the hepatic and cardiac histoarchitecture. Collectively, these results indicate that RUT-SeNPs may represent a promising nanoformulation for reducing cisplatin-induced hepato-cardiac toxicity through coordinated modulation of oxidative stress, inflammation, endoplasmic reticulum stress, and apoptosis.<\/jats:p>","DOI":"10.3390\/ijms27167430","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T16:12:58Z","timestamp":1787155978000},"page":"7430","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Rutin-Functionalized Selenium Nanoparticles Attenuate Cisplatin-Induced Cardiohepatic Injury in Rats: Modulation of ER Stress-Related Gene Expression and Mitochondrial Apoptotic Markers"],"prefix":"10.3390","volume":"27","author":[{"given":"Nievin Ahmed","family":"Mahran","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Faculty of Biotechnology, Sinai University, Kantara Branch, Ismailia 41636, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1140-8338","authenticated-orcid":false,"given":"Khaled M.","family":"Alam-ELDein","sequence":"additional","affiliation":[{"name":"School of Biotechnology, Badr University in Cairo, Cairo 11829, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7390-8592","authenticated-orcid":false,"given":"Mohamed A.","family":"Ali","sequence":"additional","affiliation":[{"name":"School of Biotechnology, Badr University in Cairo, Cairo 11829, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid M.","family":"Alsyaad","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, King Khalid University, Abha 61413, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rabab Mohamed","family":"Aljarari","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Science, University of Jeddah, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1472-8337","authenticated-orcid":false,"given":"Reem S.","family":"Alazragi","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Science, University of Jeddah, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha","family":"Alsunbul","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salma M.","family":"Selim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Toxicology, Faculty of Pharmacy, Sinai University, Kantara Branch, Ismailia 41636, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6108-1663","authenticated-orcid":false,"given":"Ossama M.","family":"Sayed","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Faculty of Pharmacy, Sinai University, Kantara Branch, Ismailia 41612, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1976-9480","authenticated-orcid":false,"given":"Mohamed H. 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