Effect of Levetiracetam on Oxidant-Antioxidant Activity during Long-Term Temporal Lobe Epilepsy in Rats – PubMed Black Hawk Supplements

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Epilepsy is a disorder characterized by a predisposition to generate seizures. Levetiracetam (LEV) is an antiseizure drug that has demonstrated oxidant-antioxidant effects during the early stages of epilepsy in several animal models. However, the effect of LEV on oxidant-antioxidant activity during long-term epilepsy has not been studied. Therefore, the objective of the present study was to determine the effects of LEV on the concentrations of five antioxidant enzymes and on the levels of four…
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Effect of Levetiracetam on Oxidant-Antioxidant Activity during Long-Term Temporal Lobe Epilepsy in Rats - PubMed

Effect of Levetiracetam on Oxidant-Antioxidant Activity during Long-Term Temporal Lobe Epilepsy in Rats

Iván Ignacio-Mejía et al. Int J Mol Sci. .

Abstract

Epilepsy is a disorder characterized by a predisposition to generate seizures. Levetiracetam (LEV) is an antiseizure drug that has demonstrated oxidant-antioxidant effects during the early stages of epilepsy in several animal models. However, the effect of LEV on oxidant-antioxidant activity during long-term epilepsy has not been studied. Therefore, the objective of the present study was to determine the effects of LEV on the concentrations of five antioxidant enzymes and on the levels of four oxidant stress markers in the hippocampus of rats with temporal lobe epilepsy at 5.7 months after status epilepticus (SE). The results revealed that superoxide dismutase (SOD) activity was significantly greater in the epileptic group (EPI) than in the control (CTRL), CTRL + LEV and EPI + LEV groups. No significant differences were found among the groups’ oxidant markers. However, the ratios of SOD/hydrogen peroxide (H2O2), SOD/glutathione peroxidase (GPx) and SOD/GPx + catalase (CAT) were greater in the EPI group than in the CTRL and EPI + LEV groups. Additionally, there was a positive correlation between SOD activity and GPx activity in the EPI + LEV group. LEV-mediated modulation of the antioxidant system appears to be time dependent; at 5.7 months after SE, the role of LEV may be as a stabilizer of the redox state.

Keywords: antioxidant enzymes; levetiracetam; long-term epilepsy; oxidant markers; oxidative stress; temporal lobe epilepsy.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1

Antioxidant marker levels in the hippocampus of rats. (AE) show the values of SOD, CAT, GPx and GR activities and GSH levels, respectively. For all measurements, each quantification was performed in triplicate via data from the CTRL (n = 4), CTRL + LEV (n = 5), EPI (n = 5) and EPI + LEV (n = 6) groups; the values are presented as the means ± SEMs. Differences were analyzed via one-way ANOVA and Tukey’s post hoc test. The brackets indicate the groups that are significantly different. ** p < 0.01 indicates a significant difference.

Figure 2
Figure 2

Oxidant levels in the hippocampi of rats. (AD) show the oxidant levels of H2O2, carbonyl proteins, MDA and 8-OHdG, respectively. For all measurements, each quantification was performed in triplicate via data from the CTRL (n = 4), CTRL + LEV (n = 5), EPI (n = 5) and EPI + LEV (n = 6) groups; the values are presented as the means ± SEMs. Differences were analyzed via one-way ANOVA and Tukey’s post hoc test. No significant differences were found among the groups.

Figure 3
Figure 3

Ratio and correlation analysis of oxidant–antioxidant levels in the hippocampus. (AC) show the ratios of SOD/H2O2, SOD/GPx and SOD (GPx + CAT), respectively. The values are presented as the means ± SEMs. Differences were analyzed via one-way ANOVA and the post hoc Student–Newman–Keuls test. The brackets indicate the groups that are significantly different. * p < 0.05, ** p < 0.01 and *** p < 0.001 indicate significant differences from the CTRL (n = 4), CTRL + LEV (n = 5), EPI (n = 5) and EPI + LEV (n = 6) groups. (D) The correlation of GPx/SOD activity in the EPI + LEV group; Pearson’s correlation, p < 0.01.

Figure 4
Figure 4

Experimental design. At time 0, all the groups were pretreated with lithium chloride. On day 1, all the animals in the EPI and EPI + LEV groups were administered methylscopolamine bromide, and status epilepticus was induced with pilocarpine. At week 22, the rats were video-recorded for 9 days to observe spontaneous recurrent seizures. Additionally, during this week, osmotic minipumps were implanted in the EPI + LEV and CTRL + LEV groups to provide subchronic treatment with levetiracetam. At week 23, blood and brain samples were obtained. LEV, levetiracetam; CTRL, control; EPI, epileptic.

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Effect of Levetiracetam on Oxidant-Antioxidant Activity during Long-Term Temporal Lobe Epilepsy in Rats – PubMed