{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T02:03:49Z","timestamp":1784253829403,"version":"3.55.0"},"reference-count":76,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Acute cerebral ischemia is characterized by excessive oxidative stress and impaired antioxidant defense mechanisms, in which the nuclear factor erythroid 2\u2013related factor 2 (Nrf2)\u2013Kelch-like ECH-associated protein 1 (Keap1) signaling pathway plays a pivotal regulatory role. This study aimed to investigate serum levels of Nrf2\u2013Keap1 pathway components and associated oxidative stress biomarkers in patients with acute ischemic stroke. Materials and Methods: Eighty-eight patients diagnosed with ischemic stroke who presented within 24 h of the onset of neurological deficit and met the inclusion criteria, along with 72 healthy control subjects without a history of acute ischemic stroke, were included in the study. Serum levels of Nrf2, Keap1, glycogen synthase kinase-3\u03b2 (GSK-3\u03b2), heme oxygenase-1 (HO-1), glutathione (GSH), and 4-hydroxynonenal (4-HNE) were quantified using enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic performance of the biomarkers. Results: Compared with controls, patients exhibited significantly reduced Nrf2 levels and markedly elevated Keap1 and 4-HNE levels. HO-1 and GSH concentrations were also significantly increased in the patient group, whereas GSK-3\u03b2 levels did not differ significantly between groups. ROC analysis demonstrated that 4-HNE and Nrf2 possessed the highest discriminative capacity for acute ischemic stroke. Conclusions: These findings suggest that acute cerebral ischemia is associated with dysregulation of the Nrf2\u2013Keap1 axis accompanied by enhanced lipid peroxidation and oxidative burden. Although increased HO-1 and GSH levels may reflect a compensatory antioxidant response, elevated 4-HNE levels indicate persistent oxidative injury.<\/jats:p>","DOI":"10.3390\/medicina62071371","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:55:59Z","timestamp":1784249759000},"page":"1371","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of the Nrf2-Keap1 Pathway in Patients with Acute Cerebral Ischemic Disease"],"prefix":"10.3390","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7874-2577","authenticated-orcid":false,"given":"Gizem","family":"Alkan","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine, Gaziantep University, Gaziantep 27310, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9179-2685","authenticated-orcid":false,"given":"Fatih","family":"Ko\u00e7t\u00fcrk","sequence":"additional","affiliation":[{"name":"Department Neurology, Faculty of Medicine, Kahramanmaras Sutcu Imam University, Kahramanmaras 46050, Turkey"},{"name":"Department Neurology,  Faculty of Medicine, Gaziantep University, Gaziantep 27310, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5392-9358","authenticated-orcid":false,"given":"Ay\u015fe","family":"Karakus","sequence":"additional","affiliation":[{"name":"Department Neurology,  Faculty of Medicine, Gaziantep University, Gaziantep 27310, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7419-5988","authenticated-orcid":false,"given":"Muhammed Enes","family":"Taysi","sequence":"additional","affiliation":[{"name":"Division of Emergency Medicine, Cankiri State Hospital, Cankiri 18100, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1251-3148","authenticated-orcid":false,"given":"Seyithan","family":"Taysi","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine, Gaziantep University, Gaziantep 27310, Turkey"},{"name":"Phytotherapy and Medicinal-Aromatic Plants Application and Research Center, Gaziantep University, Gaziantep 27310, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Krishnamurthy, H.K., Pereira, M., Rajavelu, I., Jayaraman, V., Krishna, K., Wang, T., Bei, K., and Rajasekaran, J.J. 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