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Effects of Levetiracetam in Lipid Peroxidation Level, Nitrite–Nitrate Formation and Antioxidant Enzymatic Activity in Mice Brain After Pilocarpine-Induced Seizures

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Oxidative stress has been implicated in a large number of human degenerative diseases, including epilepsy. Levetiracetam (LEV) is a new antiepileptic agent with broad-spectrum effects on seizures and animal models of epilepsy. Recently, it was demonstrated that the mechanism of LEV differs from that of conventional antiepileptic drugs. Objectifying to investigate if LEV mechanism of action involves antioxidant properties, lipid peroxidation levels, nitrite–nitrate formation, catalase activity, and glutathione (GSH) content were measured in adult mice brain. The neurochemical analyses were carried out in hippocampus of animals pretreated with LEV (200 mg/kg, i.p.) 60 min before pilocarpine-induced seizures (400 mg/kg, s.c.). The administration of alone pilocarpine, 400 mg/kg, s.c. (P400) produced a significant increase of lipid peroxidation level in hippocampus. LEV pretreatment was able to counteract this increase, preserving the lipid peroxidation level in normal value. P400 administration also produced increase in the nitrite–nitrate formation and catalase activity in hippocampus, beyond a decrease in GSH levels. LEV administration before P400 prevented the P400-induced alteration in nitrite–nitrate levels and preserved normal values of catalase activity in hippocampus. Moreover, LEV administration prevented the P400-induced loss of GSH in this cerebral area. The present data suggest that the protective effects of LEV against pilocarpine-induced seizures can be mediated, at least in part, by reduction of lipid peroxidation and hippocampal oxidative stress.

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ACKNOWLEDGMENTS

The authors are thankful for the kind donation of levetiracetam from UCB Pharmaceutical Sector. The useful comments of Dr. Alain Matagne and UCB reviewers are also gratefully acknowledged. This work was supported by research grants from the Brazilian National Research Council (CNPq). A.A.O., R.M.F., and L.M.V.A are Fellows from CNPq.

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  1. Laboratory of Neuropharmacology, Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Rua Cel. Nunes de Melo 1127, Fortaleza, 60431-970, CE, Brazil

    A. A. Oliveira, J. P. C. Almeida, R. M. Freitas, V. S. Nascimento, L. M. V. Aguiar, H. V. N. Júnior, F. N. Fonseca, G. S. B. Viana, F. C. F. Sousa & M. M. F. Fonteles

  2. Department of Pharmacy, School of Pharmacy, Dentistry, and Nursing, Federal University of Ceará, Fortaleza, Brazil

    M. M. F. Fonteles

  3. Rua Padre Frota 189, Monte Castelo, Fortaleza, 60325-160, Ceará,, Brazil

    A. A. Oliveira

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  1. A. A. Oliveira
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  2. J. P. C. Almeida
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Oliveira, A.A., Almeida, J.P.C., Freitas, R.M. et al. Effects of Levetiracetam in Lipid Peroxidation Level, Nitrite–Nitrate Formation and Antioxidant Enzymatic Activity in Mice Brain After Pilocarpine-Induced Seizures. Cell Mol Neurobiol 27, 395–406 (2007). https://doi.org/10.1007/s10571-006-9132-y

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