Epilepsy is considered one of the most common neurological disorders. The focus of this review is the acquired
form of epilepsy, with the development process consisting of three major phases, the acute injury phase, the latency
epileptogenesis phase, and the phase of spontaneous recurrent seizures. Nowadays, an increasing attention is paid to the
possible interrelationship between oxidative stress resulting in disturbance of physiological signalling roles of calcium and
free radicals in neuronal cells and mitochondrial dysfunction, cell damage, and epilepsy. The positive stimulation of
mitochondrial calcium signals by reactive oxygen species and increased reactive oxygen species generation resulting from
increased mitochondrial calcium can lead to a positive feedback loop. We propose that calcium can pose both,
physiological and pathological effects of mitochondrial function, which can lead in neuronal cell death and consequent
epileptic seizures. Various antiepileptic drugs may impair the endogenous antioxidative ability to prevent oxidative stress.
Therefore, some antiepileptic drugs, especially from the older generation, may trigger oxygen-dependent tissue injury.
The prooxidative effects of these antiepileptic drugs might lead to enhancement of seizure activity, resulting in loss of
their efficacy or apparent functional tolerance and undesired adverse effects. Additionally, various reactive metabolites of
antiepileptic drugs are capable of covalent binding to macromolecules which may lead to deterioration of the epileptic
seizures and systemic toxicity. Since neuronal loss seems to be one of the major neurobiological abnormalities in the
epileptic brain, the ability of antioxidants to attenuate seizure generation and the accompanying changes in oxidative
burden, further support an important role of antioxidants as having a putative antiepileptic potential.
Keywords: Antiepileptic drugs, antioxidants, calcium, epileptogenesis, mitochondria, oxidative stress, reactive species,
Rights & PermissionsPrintExport