Enhanced oxidative stress and impaired antioxidant defense in drug-resistant epilepsy

Oxidative stress is increasingly recognized as a key contributor to epileptogenesis and seizure-related neuronal injury, particularly in drug-resistant epilepsy (DRE). Persistent seizures may promote cumulative oxidative damage; however, comprehensive evaluation of ischemia-related stress, antioxidant capacity, and protein oxidation in DRE remains limited.

To comprehensively assess oxidative stress status in patients with drug-resistant epilepsy by measuring ischemia-modified albumin (IMA), total sulfhydryl (TSH) levels, and protein carbonyl (PC) concentrations.

In this cross-sectional study, serum IMA, TSH, and PC levels were measured in patients with drug-resistant epilepsy and age- and sex-matched healthy controls using standardized spectrophotometric methods. Between-group comparisons were performed to characterize oxidative imbalance associated with DRE.

Thirty-three patients with drug-resistant epilepsy and 32 healthy controls were included. Serum IMA levels were significantly higher in patients with drug-resistant epilepsy than in controls (2.07 ± 0.02 vs 1.04 ± 0.02 AU, p < 0.001). Similarly, protein carbonyl levels were significantly elevated (0.49 ± 0.02 vs 0.24 ± 0.03 µmol/mL serum, p < 0.001), whereas total sulfhydryl levels were significantly reduced (3.17 ± 0.03 vs 6.34 ± 0.10 nmol/mg protein, p < 0.001). These findings collectively indicate a marked shift toward a pro-oxidative state in drug-resistant epilepsy.

Drug-resistant epilepsy is associated with enhanced oxidative stress characterized by ischemia-related modification, irreversible protein oxidation, and depletion of antioxidant defenses. The combined assessment of IMA, TSH, and PC provides an integrated biochemical profile of oxidative imbalance in DRE and may contribute to a better understanding of seizure-related neurobiological mechanisms. These findings may provide insights for future research on therapeutic strategies targeting oxidative pathways.