Targeting mitochondrial dysfunction and apoptosis in 5-fluorouracil–induced cardiotoxicity using kaempferol-mediated selenium nanoparticles

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Nasr S.M.; Gad A.M.; Taha S.A.; Hindam N.H.; Mohamed M.R.; Badawy A.G.; Ali M.M.; Abdelaziz M.M.; Alam-ElDein K.M.; Gadelmawla M.H.A.

Journal: Scientific Reports

Publisher: Nature Research

Publication Date: 12 September 2026

Volume / Issue: Volume 16 / Issue 1

Article No.: 28495

ISSN: 20452322

DOI: 10.1038/s41598-026-69038-9

Scopus: View on Scopus

PubMed: 42732004

Document Type: Article

Access: All Open Access; Gold Open Access; Green Open Access

Authors and Affiliations

Nasr S.M., School of Biotechnology, Badr University in Cairo, Cairo, Badr City, 11829, Egypt, Department of Biochemistry and Molecular Biology, Theodor Bilharz Research Institute, Giza, Egypt; Gad A.M., School of Biotechnology, Badr University in Cairo, Cairo, Badr City, 11829, Egypt; Taha S.A., School of Biotechnology, Badr University in Cairo, Cairo, Badr City, 11829, Egypt; Hindam N.H., School of Biotechnology, Badr University in Cairo, Cairo, Badr City, 11829, Egypt; Mohamed M.R., School of Biotechnology, Badr University in Cairo, Cairo, Badr City, 11829, Egypt; Badawy A.G., School of Biotechnology, Badr University in Cairo, Cairo, Badr City, 11829, Egypt; Ali M.M., School of Biotechnology, Badr University in Cairo, Cairo, Badr City, 11829, Egypt; Abdelaziz M.M., Molecular Biology and Biotechnology Department, School of Biotechnology, Badr University in Cairo, Cairo, Badr City, 11829, Egypt; Alam-ElDein K.M., Molecular Biology and Biotechnology Department, School of Biotechnology, Badr University in Cairo, Cairo, Badr City, 11829, Egypt; Gadelmawla M.H.A., Molecular Biology and Biotechnology Department, School of Biotechnology, Badr University in Cairo, Cairo, Badr City, 11829, Egypt, Histology Department, School of Biotechnology, Badr University in Cairo, Cairo, Badr City, 11829, Egypt

Abstract

5-Flurouracil (5-FU) is still considered as one of the most popular antimetabolite chemotherapy drugs to treat a wide variety of solid tumors. 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, Na2SeO3&5-FU, KMP&5-FU, and KMP-SeNPs&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-α, IL-6, NF-κB, 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. © The Author(s) 2026.

Keywords

5-FU; Apoptosis; Cardiotoxicity; Inflammation; Kaempferol; Nanoparticle; Animals; Antioxidants; Fluorouracil; Kaempferols; Male; Mitochondria; Nanoparticles; Oxidative Stress; Rats; Rats, Wistar; Selenium; antioxidant; kaempferol derivative; animal; chemistry; drug effect; drug therapy; etiology; metabolism; mitochondrion; pathology; rat; Wistar rat

Citation Information

Scopus Citations: 0

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