Evaluation of the Nrf2-Keap1 Pathway in Patients with Acute Cerebral Ischemic Disease

Background and Objectives: Acute cerebral ischemia is characterized by excessive oxidative stress and impaired antioxidant defense mechanisms, in which the nuclear factor erythroid 2–related factor 2 (Nrf2)–Kelch-like ECH-associated protein 1 (Keap1) signaling pathway plays a pivotal regulatory role. This study aimed to investigate serum levels of Nrf2–Keap1 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-3β (GSK-3β), 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-3β 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–Keap1 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.