Modulation of Antioxidant Enzymatic Activities by Certain Antiepileptic Drugs (Valproic Acid, Oxcarbazepine, and Topiramate): Evidence in Humans and Experimental Models
Table 2
Effect of AEDs on the activity of antioxidant enzymes or oxidative stress markers in epileptic patients.
Cengiz et al., in 2000, evaluated the effect of VPA and carbamazepine on the levels of GSH, GPx, SOD, and lipid peroxidation in the erythrocytes of 30 children diagnosed with epilepsy and compared with 25 healthy children. The authors found that during a one-year treatment with VPA (in 16 children) or carbamazepine (in 14 children), the GPx levels were significantly increased, but the GSH levels were significantly decreased. With combined drugs, they were no significant differences in the SOD activity and lipid peroxidation levels.
Yksel et al., in 2001 and 2000, found a significant increase in the levels of lipid peroxidation and decreased GPx activity in the serum of 14 children treated with VPA for two years compared with that found in 27 healthy children. The SOD serum levels increased significantly during the first year. In 13 children diagnosed with epilepsy and then treated with carbamazepine for two years, lipid peroxidation increased significantly in the serum, compared with the control group. During the second year of treatment with carbamazepine, the serum SOD levels were significantly higher, compared with the control group and with the same group before treatment.
Verrotti et al., in 2002, found that 36 children with epilepsy and no treatment exhibited no significant differences in the serum levels of Se, GPx, and Cu/Zn-SOD, compared with the control group (14 children). One year after beginning therapy with VPA (in 22 patients) or carbamazepine (in 14 patients), the values of these parameters were unchanged.
Solowiej and Sobaniec, in 2003, found that 25 children treated with VPA, 16 children treated with carbamazepine, and 27 children treated with polytherapy (carbamazepine + VPA) exhibited a significant decrease in the serum SOD activity, compared with 61 healthy children. The serum GPx activity was significantly increased in all patient groups except in those receiving combination therapy, compared with the control group. The lipid peroxidation levels in the serum were significantly increased in all patients.
Hamed et al., in 2004, found that 14 adult patients without treatment exhibited no significant decrease in GPx activity but exhibited a significant reduction in the total antioxidant capacity in the serum. Fifty-five patients with epilepsy treated using VPA exhibited a significant increase in their serum GPx levels and total antioxidant capacity.
Bolayir et al., in 2004, found that the GPx activity, SOD activity, and lipid peroxidation levels in erythrocytes were significantly different after one year of therapy with oxcarbazepine. This study was performed in 13 adult patients, and the results were compared with the results obtained from 15 healthy adults and from the same patients before monotherapy.
Sobaniec et al., in 2006, evaluated the effect of therapy with AEDs and how these drugs changed the SOD, GPx, and GR activity and the lipid peroxidation levels in the erythrocytes of 90 pediatric patients and 61 healthy children. The activity of the antioxidant enzymes was significantly higher. The lipid peroxidation levels were significantly lower in children treated only with carbamazepine. In children treated with VPA, the activity of all antioxidant enzymes was lower. Higher levels of lipid peroxidation were concurrently demonstrated. In patients treated with combination therapy, the SOD activity was lower, whereas the activity of GPx and GR was higher. In addition, lower lipid peroxidation levels were displayed.
Peker et al., in 2009, investigated the effect of VPA on the serum levels of NO, lipid peroxidation, and certain antioxidant enzymes (SOD and CAT) in 21 children treated with VPA for one year and in 26 healthy children. We observed a significant increase of 10% in the levels of NO in children treated with VPA, compared with healthy children. There were no significant differences in the levels of lipid peroxidation and antioxidant enzymes.
Gneş et al., in 2009, analyzed the erythrocyte antioxidant status of 31 children with febrile seizures and 30 febrile children without seizures. The levels of lipid peroxidation were significantly higher, and the GPx and SOD levels were significantly lower in the group of children with febrile seizures compared with the group that did not present with seizures.
Varoglu et al., in 2010, determined in 32 patients treated with VPA, 17 treated with carbamazepine, 8 with levetiracetam, and 11 with polytherapy that the levels of low-density lipoprotein (LDL) and 8-OHG were significantly higher in all patients, compared with the control group. Comparing the monotherapy versus the polytherapy, only the valproate + levetiracetam combination yielded a significant increase in 8-OHG.
Arhan et al., in 2011, found a significant decrease in the serum levels of NO and lipid peroxidation in 16 children diagnosed with idiopathic epilepsy and treated for three months with OXC.
Y.J. Zhang et al., in 2011, reported a significant decrease in the antioxidant activity of SOD and CAT. They also found a significant increase in the MPO activity and lipid peroxidation levels. This study was performed in 26 epileptic children treated for six and 12 months with VPA, compared with 30 healthy children.
