Deferoxamine Attenuates Seizure Stages, Oxidative Stress, and Apoptosis via Iron Chelation in a PTZ-Induced Epilepsy Model

Abstract

Recent evidence suggests that excessive iron accumulation contributes to oxidative stress and neuronal injury, which is a key factor in epilepsy development. To address this, our study evaluated the effects of deferoxamine (DFO), an iron chelator, on seizure severity, oxidative stress, and apoptosis in a rat model of epilepsy triggered by pentylenetetrazole (PTZ). Eighteen male Wistar albino rats were randomly allocated into three experimental groups: Control, PTZ, and PTZ + DFO. Animals received either DFO (250 mg/kg, i.p.) or saline 30 minutes prior to PTZ administration (45 mg/kg, i.p.). Seizure onset and severity were assessed using Racine's Convulsion Scale. Hippocampal tissues were analyzed for total oxidant status (TOS) and total antioxidant status (TAS) as well as caspase-3 and caspase-9 levels. DFO pretreatment significantly reduced seizure stage and prolonged the latency to both the first myoclonic jerk and generalized tonic-clonic seizures relative to the PTZ group. Biochemical analyses revealed that DFO significantly reduced TOS and increased TAS in hippocampal tissue. Additionally, caspase-3 and caspase-9 levels were significantly lower in the PTZ + DFO group relative to the PTZ group. Deferoxamine attenuates seizure severity and delays seizure onset, likely through mechanisms involving iron chelation, antioxidant defense enhancement, and inhibition of apoptosis. These results highlight DFO's neuroprotective capacity, underscoring its possible utility in the management of epileptic disorders.