Role of oxidative stress in epileptogenesis and potential implications for therapy
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REVIEW
Role of oxidative stress in epileptogenesis and potential implications for therapy Kinga K. Borowicz‑Reutt1 · Stanisław J. Czuczwar2 Received: 23 May 2020 / Revised: 15 July 2020 / Accepted: 16 July 2020 © The Author(s) 2020
Abstract In a state of balance between oxidants and antioxidants, free radicals play an advantageous role of “redox messengers”. In a state of oxidative stress, they trigger a cascade of events leading to epileptogenesis. During this latent, free of seizures period, a cascade of neurological changes takes place and finally leads to spontaneous recurrent seizures. The main processes involved in seizure generation are: neuroinflammation, neurodegeneration with anomalous neuroregeneration and lowering seizure threshold. Time of epileptogenesis offers a unique therapeutic window to prevent or at least attenuate seizure development. Animal data indicate that some antioxidants (for instance, resveratrol) may bear an anti-epileptogenic potential. Keywords Free radicals · Oxygen species · Nitrogen species · Oxidative stress · Epileptogenesis
Introduction In both experimental and clinical conditions, antiseizure drugs (ASDs) were generally found disappointing in the aspect of neuroprotection and prevention of epileptogenesis [1–5]. Therefore, searching for not only antiseizure but also anti-epileptogenic strategies may become a new promising possibility to overcome problems associated with the treatment of drug-resistant epilepsy. Production of reactive oxygen (ROS) and nitrogen species (RNS) is unavoidable even under physiological conditions. By definition, free radicals are atoms or their groups containing at least one unpaired electron on the outer shell. Molecular oxygen reduced by one electron makes superoxide (O2−•). One electron more leads to hydrogen peroxide (H2O2) generation, which is not a free radical, but when reduced to hydroxyl peroxide (HO•), it becomes the strongest oxidant currently known [6]. Produced superoxide can react with nitric oxide to form a very reactive peroxynitrite (ONOO −), another source of hydroxyl radical [6–8].
* Kinga K. Borowicz‑Reutt [email protected] 1
Independent Unit of Experimental Pathophysiology, Medical University of Lublin, Lublin, Poland
Department of Pathophysiology, Medical University of Lublin, 20‑090 Lublin, Poland
2
The mitochondrial respiratory chain provides production of around 90% of all free radicals. Other enzymes involved in the oxidative stress are: microsomal cytochrome P450 enzymes, flavoprotein oxidases, peroxysomal fatty acid oxidases [9]. Particularly important seem to be NADPH oxidase (Nox2), increasing superoxide production, and cyclooxygenase-2 (COX-2), stimulating astrocytes to synthesize proinflammatory cytokines [3]. Presently, Nox2 is considered as the main source of ROS at initial stages of epileptogenesis and neurodegeneration [10, 11]. Oxidative stress, understood as an imbalance between pro- and antioxidants, may prove highly harmful to cells, causing their damage and death. The first evidence tha
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