Iron Metabolism Disorders and Mechanisms of Ferroptosis in the Pathogenesis of Focal Epilepsy

Abstract

To evaluate alterations in iron metabolism markers and ferroptosis biomarkers in patients with focal epilepsy and determine their association with disease severity. Materials and Methods: The study included 85 patients with focal epilepsy and 40 healthy individuals as a control group. Serum levels of iron, ferritin, transferrin, transferrin saturation, hepcidin, ceruloplasmin, as well as ferroptosis biomarkers (GPX4, ACSL4, PTGS2), were measured in all participants. The frequency and severity of epileptic seizures were assessed. Results: Compared with the control group, patients with focal epilepsy had significantly lower serum iron levels (12.8±2.1 µmol/L vs. 18.4±1.9 µmol/L, p<0.001) and higher ferritin levels (285.7±45.2 ng/mL vs. 156.3±28.7 ng/mL, p<0.001). Among ferroptosis biomarkers, GPX4 activity was significantly reduced (0.42±0.08 U/mL vs. 0.78±0.12 U/mL, p<0.001), while ACSL4 and PTGS2 levels were increased (p<0.01). A negative correlation was found between seizure frequency and iron deficiency (r = -0.67, p<0.001), as well as GPX4 activity (r = -0.58, p<0.001). Conclusion: In focal epilepsy, disturbances in iron metabolism and activation of ferroptosis processes play an important role in the disease pathogenesis and reveal new potential therapeutic targets.