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Effects of Antiepileptic Drugs on Antioxidant and Oxidant Molecular Pathways: Focus on Trace Elements

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Abstract

Current reports on trace elements, oxidative stress, and the effect of antiepileptic drugs are poor and controversial. We aimed to review effects of most common used antiepileptics on antioxidant, trace element, calcium ion (Ca2+) influx, and oxidant systems in human and experimental animal models. Observations of lower blood or tissue antioxidant levels in epileptic patients and animals compared to controls in recent publications may commonly support the proposed crucial role of antioxidants in the pathogenesis of epilepsy. Effects of old and new antiepileptics on reactive oxygen species (ROS) production in epilepsy are controversial. The old antiepileptic drugs like valproic acid, phenytoin, and carbamazepine induced ROS overproduction, while new epileptic drugs (e.g., topiramate and zonisamide) induced scavenger effects on over production of ROS in human and animals. Antioxidant trace element levels such as selenium, copper, and zinc were generally low in the blood of epileptic patients, indicating trace element deficiencies in the pathogenesis of epilepsy. Recent papers indicate that selenium with/without topiramate administration in human and animals decreased seizure levels, although antioxidant values were increased. Recent studies also reported that sustained depolarization of mitochondrial membranes, enhanced ROS production and Ca2+ influx may be modulated by topiramate. In conclusion, there is a large number of recent studies about the role of antioxidants or neuroprotectants in clinical and experimental models of epilepsy. New antiepileptic drugs are more prone to restore antioxidant redox systems in brain and neurons.

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Abbreviations

AMPA:

Alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid

Cu:

Copper

GSH:

Glutathione

GSH-Px:

Glutathione peroxidase

MDA:

Malondialdehyde

NFkB:

Nuclear factor kappa B

NMDA:

N-methyl-d-aspartate

PTZ:

Pentylenetetrazole

ROS:

Reactive oxygen species

Se:

Selenium

SOD:

Superoxide dismutase

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  1. Neurocience Research Center, Suleyman Demirel University, Tıp Fakültesi Binasi, 32260, Isparta, Turkey

    Mustafa Nazıroğlu

  2. Department of Neurology, Medical Faculty, Suleyman Demirel University, Isparta, Turkey

    Vedat Ali Yürekli

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Correspondence to Mustafa Nazıroğlu.

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Nazıroğlu, M., Yürekli, V.A. Effects of Antiepileptic Drugs on Antioxidant and Oxidant Molecular Pathways: Focus on Trace Elements. Cell Mol Neurobiol 33, 589–599 (2013). https://doi.org/10.1007/s10571-013-9936-5

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