Plasma Trace Element, Plasma Glutathione Peroxidase, and Superoxide Dismutase Levels in Epileptic Children Receiving Antiepileptic Drug Therapy

Abstract

Some antiepileptic drugs (AEDs) may alter trace element metabolism and free radical scavenging enzyme activities in humans and experimental animals. We investigated the effect of long-term AED therapy on copper (Cu), zinc (Zn), manganese (Mn), selenium (Se), magnesium (Mg), glutathione peroxidase (GSH-PX), and superoxide dismutase (SOD) in the plasma in children with epilepsy. During treatment with valproate (VPA) or carbamazepine (CBZ) monotherapy plasma Cu, Zn, Mn, Se, and Mg concentrations of patients were not statistically different from those of control subjects. The level of serum VPA weakly correlated with the increase in plasma Zn level. Recent studies suggest that membrane lipid peroxidation may be causally involved in some forms of epilepsies, and the decreased free radical scavenging enzyme activity is believed to cause the increased risk of an idiosyncratic drug reaction encountered in the management of epilepsy. Because GSH-PX and SOD are the most important members of antioxidant defense mechanisms, we quantitated the activities of these enzymes in plasma of children with epilepsy receiving VPA or CBZ. Only plasma GSH-PX activities in VPA group were higher than those of the control group, and the difference was statistically significant.

Blood Levels of Trace Elements, Electrolytes, and Oxidative Stress/Antioxidant Systems in Epileptic Patients

“…In our study, the untreated epileptics exhibited unaltered Zn 2+ levels and the VPAtreated epileptics showed significantly higher level of Zn 2+ (P<0.05) ( Tables 2 and 4 (35), the serum and hair levels of Zn 2+ were found to be higher in untreated epileptic patients than those treated with VPA and controls and returned to normal level after VPA treatment. Consistent with our study, Kürekçi et al (12) reported higher levels of Zn 2+ in treated groups of patients that remained within the normal range and attributed this to the normal physiological variation in serum Zn 2+ concentrations (circadian variation) and is unlikely related to the anticonvulsant drugs or epilepsy (36,37). Others attributed the increased serum Zn 2+ levels to measuring such levels at least 2 h later than VPA intake, that is, at the peak of VPA concentration (38).…”

“…Free radical scavenging activity was indicated by the total antioxidant capacity (TAC). Antioxidant defense mechanisms was indicated to involve glutathione peroxidase (GSH-Px), which is one of the most important members of the body antioxidant defense systems (8), copper (Cu 2+ ) (9,10), zinc (Zn 2+ ) (9,11,12), sele-nium (Se 2+ ) (13), ceruloplasmin (Crl) (a copper-binding protein), and uric acid (6,14,15).…”

The Predictors of Early Atherosclerosis in Young Adult Epileptic Patients

“…We also observed slightly higher GPX level in VPA group and poly-therapy Ali M.; et al… -67-group than CBZ group although the difference was not significant. This is in agreement with others [35,36,38] . Hamed et al [5] demonstrated marked reduction in GPX levels among the untreated patients and elevated to normal levels with AED medications.…”

Association of antiepileptic drug usage, trace elements and thyroid hormone status

“…Unfortunately, these measurements were performed during treatment with AEDs; therefore, no data is available on pre-or post-treatment levels. Many studies described the effects of AEDs on trace element levels like Se and Cu, although the effects of different classes of AEDs were neither consistent in magnitude nor in direction (29,30,31,32,35,36,37). There are several potential reasons for these inconsistencies, ranging from dosage and duration of AED usage, age, health, and nutritional status of the patients to baseline trace element concentrations which differ profoundly in different geographical areas as well as the small number of subjects studied (38).…”

“…It has been speculated that the changed thyroid parameters in patients that use AEDs can be explained by an influence of AEDs on binding proteins (27), a stimulation of hepatic degradation or conjugation of TH (28) or an altered peripheral deiodinase activity (23). Interestingly, AEDs have been associated with changes in serum levels of Se and Cu (23,29,30,31,32,33). However, the complex relationship between AEDs, THs, Se, and Cu has never been directly studied.…”