**1. Introduction**

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3.

#### **1.1. Epilepsy and oxidative stress**

Epilepsy is a common chronic neurological disorder with a prevalence of 0, 4 – 1 % of the general population [1]. The highest incidence rates are in children and elderly. Epilepsy is characterized by recurrent unprovoked seizures, generalized or focal. The epileptic seizure is a clinical manifestation of transient excessive and hyper synchronous activity of neurones in the brain. It may include alterations of consciousness, motor or autonomic components or subjective sensory or psychic phenomena. An epilepsy syndrome is a complexity of signs and symptoms defining a unique condition. One of the most common syndromes is Juvenile myoclonic epilepsy accounting for up to 10% of all epilepsies [2].

Etiology of epilepsy in the majority is not identified [3]. Genetic defect or structural-metabolic disorder of the brain may be the cause of some chronic seizures. The commonest acquired causes of epilepsy include vascular diseases, tumours, trauma, and infections of the central nervous system [2]. However, the mechanisms of epileptogenesis are not well understood.

Experimental and human studies suggested that the homeostasis of trace elements and membrane lipid peroxidation due to increase of free radicals or decreased of antioxidant defence mechanisms have been causally involved in some forms of epilepsies. They were directly or indirectly implicated as taking part in the pathophysiology of neuronal excitability, neuronal excitotoxicity, seizure recurrence and its resistance to treatment with antiepileptic drugs [4].

© 2014 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Oxidative stress is a common pathogenic mechanism in neurodegenerative disorders. The central nervous system is particularly susceptible to reactive oxygen species (ROS) due to high oxygen demands of the brain, low concentration of endogenous antioxidants and concomitant accumulation of reactive iron. Furthermore, the abundance of polyunsaturated fatty acids and excess of predominant neurotransmitter glutamate, favour cell toxicity [5]. ROS can activate a self-accelerating vicious cycle leading to mitochondrial damage and neuronal cell death [6].

damage, it is necessary to manipulate iron to assess its causal role. In the animal model of epilepsy, iron supplementation increased damage in various brain regions, and a tight relationship between iron and zinc in micro gliosis was found [10]. In general, iron is kept safe by binding itself to protein; transported in form of transferrin-bound iron or stored in form of ferritin. The liberation of free iron can augment generation of active free radicals and it appears to play a crucial role in the posttraumatic epilepsy [11]. Iron deposition results in tissue damage by either directly damaging cells or changing the cellular environment so that it is more susceptible to toxins or other pathologic processes. On the other hand, iron is a cofactor of catalase (CAT), which plays a role in antioxidant defence systems by catalysing the decom‐ position of hydrogen peroxide. The proper balance of iron without excessive supplementation

Trace Elements, Antioxidant Enzymes and Free Carnitine Levels Among Epileptic Patients Treated with…

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The surrogate markers of iron status may be non-transferrin bound iron (NTBI). There was

The trace elements selenium (Se), cooper (Cu) and zinc (Zn) are important cofactors of antioxidant enzymes such as superoxide dismutase (Cu-SOD, Zn-SOD), glutathione peroxid‐ ise (GPX) as well as protein with antioxidant properties, ceruloplasmin (CRL, copper-binding protein). SOD and GPX play a predominant role as free radical scavengers in the brain tissue, whilst CAT is deficient [13]. SOD and GPX are also important for detoxification of xenobiotics,

Results of various studies on trace elements levels and activities of main antioxidant enzymes during pharmacotherapy of epilepsy are conflicting. A selected bias of patients and different laboratory methods might be responsible, as well as the influence of lifestyle with consumption

A decrease in the trace elements selenium and copper was reported in epileptic patients receiving sodium valproate [17]. One of the main selenium status marker is plasma glutathione peroxidise (GPX3). The product of plasma SOD (pSOD) activity, H2O2, is the major substrates for GPX3. An involvement of lipid peroxidation seems to be probable and the elevated activity of pSOD in some studies may be explained by this induction. Significant effects of duration of VPA therapy, activity of seizures and gender were found on Zn, pSOD, and erythrocyte SOD (eSOD) levels [4, 9]. Also in prospective studies [18, 19] were reported increased levels of eSOD in epileptic children after implementation of VPA treatment. Some other authors did not find a significant difference in enzyme activity or even a reduced level of pSOD was found in young

pSOD is a sensitive index of Cu status, while plasma Cu is not a reliable marker of copper status [21]. Zinc supplements can decrease SOD activity, primarily due to the antagonistic relationship between high zinc intakes and copper absorption [22, 23]. A few authors reported

found an increase in NTBI in patients treated due to epilepsy with VPA [12].

and may be involved in the oxidative injury caused by antiepileptic drugs [14].

of natural antioxidants or their supplementation [4, 15, 16].

people with epilepsy treated using valproate [20].

lower or normal Zn concentrations in persons with epilepsy [24, 25]

is very important for oxidant status.

**3.2. Selenium, cooper, zinc**

In epilepsy, the oxidative/antioxidative balance can have a role in both seizure controls and side effects of often life-long pharmacotherapy.
