Additional antiepileptic mechanisms of levetiracetam in lithium-pilocarpine treated rats.

Several studies have addressed the antiepileptic mechanisms of levetiracetam (LEV); however, its effect on catecholamines and the inflammatory mediators that play a role in epilepsy remain elusive. In the current work, lithium (Li) pretreated animals were administered LEV (500 mg/kg i.p) 30 min before the induction of convulsions by pilocarpine (PIL). Li-PIL-induced seizures were accompanied by increased levels of hippocampal prostaglandin (PG) E2, myeloperoxidase (MPO), tumor necrosis factor-α, and interleukin-10. Moreover, it markedly elevated hippocampal lipid peroxides and nitric oxide levels, while it inhibited the glutathione content. Li-PIL also reduced hippocampal noradrenaline, as well as dopamine contents. Pretreatment with LEV protected against Li-PIL-induced seizures, where it suppressed the severity and delayed the onset of seizures in Li-PIL treated rats. Moreover, LEV reduced PGE2 and MPO, yet it did not affect the level of both cytokines in the hippocampus. LEV also normalized hippocampal noradrenaline, dopamine, glutathione, lipid peroxides, and nitric oxide contents. In conclusion, alongside its antioxidant property, LEV anticonvulsive effect involves catecholamines restoration, as well as inhibition of PGE2, MPO, and nitric oxide

Effect of levetiracetam (LEV, 500 mg/kg i.p.) on hippocampal noradrenaline (NA; A) and dopamine (DA; B) in lithium-pilocarpine (Li-PIL)-induced convulsion in rats.

<p>Values are means ± S.E.M. of 6 rats as compared to control (*) and Li-PIL (^@) groups. Comparisons were carried out using one-way ANOVA followed by Student–Newman–Keuls Multiple Comparisons Test, <i>P</i><0.05.</p

Effect of levetiracetam (LEV, 500 mg/kg i.p.) on hippocampal prostaglandin (PG)E₂ (A), tumor necrosis factor (TNF)-α (B), interleukin (IL)-10 activity (C), and myeloperoxidase (MPO) (D) in lithium-pilocarpine (Li-PIL)-induced convulsion in rats.

<p>Values are means ± S.E.M. of 6 rats. As compared to control (*) and Li-PIL (^@) groups. Comparisons were carried out using one-way ANOVA followed by Student–Newman–Keuls Multiple Comparisons Test, <i>P</i><0.05.</p

Effect of levetiracetam (LEV, 500 mg/kg i.p.) on hippocampal glutathione (GSH; A), thiobarbituric acid reactive substances (TBARS; B), and nitric oxide (NO; C) in lithium-pilocarpine (Li-PIL)-induced convulsion in rats.

<p>Values are means ± S.E.M. of 6 rats. As compared to control (*) and Li-PIL (^@) groups. Comparisons were carried out using one-way ANOVA followed by Student–Newman–Keuls Multiple Comparisons Test, <i>P</i><0.05.</p