Free Radicals and Antioxidants: Opportunities for Enhancing Treatment of Epilepsy with Personalized Medicine

Abstract

Introduction: Epileptic seizures and antiepileptic drugs (AEDs) are a source of oxygen stress. Oxygen stress can have negative effects. These effects which can be prevented are largely unknown in clinical epileptology. Objective: The objective of the study is to discuss (a) homeostatic oxidant, antioxidant imbalance due to epileptic seizures and AEDs, (b) the protective factors that help prevent oxygen stress (OS), and personalized medicine based on pharmacogenomics and diet as therapeutic challenges in epilepsy. Discussion: Experimental models of epileptic seizures evoked by various means suggest that seizures can cause neuronal destruction. This is accompanied by an increased activity of free radicals and a reduction of total antioxidant capacity (in red blood cells, blood serum, and cerebrospinal fluid). A number of antioxidants have been found to attenuate the negative effects of OS and act neuroprotectively if they are administered prior to seizure occurrence: vitamins (C, E), trace elements (Se, Zn), melatonin, erdosteine, or natural herbal extracts. New AEDs (GBP, LEV, LTG, and TGB) cause no, or very little, OS as opposed to other drugs (CBZ, PHT, PB, VPA, TPM, or OXC), which have pronounced albeit heterogeneous and dose-dependent effects. It is suggested that AEDs should be administered together with free radical sweepers (vitamins, trace elements, electrolytes, melatonin) and other anti-oxidizing substances. Conclusions: (1) Epileptic seizures and AEDs cause OS. The effects vary greatly depending, among other things, on the daily drug dose. (2) The findings of research using a variety of seizure models are more unequivocal than the findings of research on patients with epilepsy. This suggests that the relations among seizures, AEDs, OS etiology, and OS consequences are complex. (3) Since existing AEDs cause OS, it is necessary to develop a new approach to AED treatment. (4) It is important to know the patient's specific characteristics, including previous history, lifestyle, age, gender, weight, diet, environment, etc. They can be valuable tools to improve the quality of life of a person suffering from epilepsy. This concept of managing the patient health is called targeted medicine or personalized medicine.

A Novel Pathway Phenotype of Temporal Lobe Epilepsy and Comorbid Psychiatric Disorders: Results of Precision Nomothetic Medicine

“…In animal models, there is some evidence that administration of antioxidants, including acetyl-carnitine, L-carnitine, Ginkgo biloba leaf extract, Lantana camara and vanillic acid, exert neuroprotective, anticonvulsant and/or anti-kindling effects [75][76][77][78][79]. There is also some evidence that in TLE patients, treatment with antioxidants such as selenium and vitamin E and C may have some efficacy [80]. Nevertheless, in preclinical models, natural polyphenols have mixed affects, and N-acetylcysteine may aggravate seizures and improve depressive-like behaviors [81,82].…”