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In this study, we investigated the effect of BPA on ferroptosis induction in endothelial cells and its association with Nrf2 signaling and endothelial dysfunction. Human endothelial cells were exposed to BPA (10, 50, and 100\u2009\u03bcM) for 24\u2009h, and the expression of ferroptosis markers (GPX4, SLC7A11, ACSL4, TFR1, FPN, FTH), Nrf2 and its downstream antioxidant enzymes (SOD2, HO\u20101, NQO1, CAT), oxidative stress markers (P22PHOX, TXNIP), inflammatory cytokines (IL\u20101\u03b2, IL\u20106, TNF\u2010\u03b1, IL\u201018), and endothelial dysfunction markers (ENDO\u20101, ICAM\u20101, VCAM\u20101, vWF) were assessed by qRT\u2010PCR and western blotting. BPA exposure downregulated GPX4, SLC7A11, FPN, and FTH while upregulating ACSL4 and TFR1, indicating ferroptotic activation. Ferroptosis induction was further confirmed by FerroOrange staining, demonstrating increased labile intracellular iron accumulation in BPA\u2010treated endothelial cells. Concurrently, Nrf2 expression and nuclear translocation were suppressed, accompanied by Keap1 upregulation, reduced levels of antioxidant enzymes, and elevated oxidative stress and proinflammatory cytokine levels. Markers of endothelial dysfunction increased significantly at higher BPA concentrations (50\u2013100\u2009\u03bcM). Collectively, these findings identify ferroptosis as a critical mediator of BPA\u2010induced endothelial dysfunction through disruption of Nrf2 signaling, highlighting potential therapeutic targets for BPA\u2010associated cardiovascular pathologies.<\/jats:p>","DOI":"10.1002\/jat.70145","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T06:35:33Z","timestamp":1773815733000},"page":"3949-3960","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Bisphenol A Induces Endothelial Dysfunction via Oxidative Stress\u2013Driven Ferroptosis and Nrf2 Suppression"],"prefix":"10.1002","volume":"46","author":[{"given":"S.","family":"Yukta","sequence":"first","affiliation":[{"name":"Department of Biotechnology, School of Bioengineering SRM Institute of Science and Technology  Kattankulathur Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Jayasuriya","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, School of Bioengineering SRM Institute of Science and Technology  Kattankulathur Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.\u00a0L.","family":"Milan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, School of Bioengineering SRM Institute of Science and Technology  Kattankulathur Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Sahabudeen","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, School of Bioengineering SRM Institute of Science and Technology  Kattankulathur Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaku","family":"Ichihara","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Health, Faculty of Pharmaceutical Sciences Tokyo University of Science  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5450-902X","authenticated-orcid":false,"given":"K.\u00a0M.","family":"Ramkumar","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, School of Bioengineering SRM Institute of Science and Technology  Kattankulathur Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,17]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(05)80494-9"},{"issue":"1","key":"e_1_2_11_3_1","first-page":"19","article-title":"The Genotoxic and Cytotoxic Effects of Bisphenol\u2010A (BPA) in MCF\u20107 Cell Line and Amniocytes","volume":"5","author":"Aghajanpour\u2010Mir S. 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