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The Effects of Alpha-Tocopherol on Hippocampal Oxidative Stress Prior to in Pilocarpine-Induced Seizures

Abstract

Reactive oxygen species have been implicated in seizure-induced neurodegeneration, and there is a correlation between free radical level and scavenger enzymatic activity in the epilepsy. It has been suggested that pilocarpine-induced seizures is mediated by an increase in oxidative stress. Current research has found that antioxidant may provide, in a certain degree, neuroprotection against the neurotoxicity of seizures at the cellular level. Alpha-tocopherol has numerous nonenzymatic actions and is a powerful liposoluble antioxidant. The objective of the present study was to evaluate the neuroprotective effects of alpha-tocopherol (TP) in rats, against oxidative stress caused by pilocarpine-induced seizures. 30 min prior to behavioral observation, Wistar rats were treated with, 0.9% saline (i.p., control group), TP (200 mg/kg, i.p., TP group), pilocarpine (400 mg/kg, i.p., P400 group), or the combination of TP (200 mg/kg, i.p.) and pilocarpine (400 mg/kg, i.p.). After the treatments all groups were observed for 6 h. The enzymatic activities, lipid peroxidation and nitrite concentrations were measured using speccitrophotometric methods and these data were assayed. In P400 group mice there was a significant increase in lipid peroxidation and nitrite levels. However, no alteration was observed in superoxide dismutase (SOD) and catalase activities. In the TP and pilocarpine co-administered mice, antioxidant treatment significantly reduced the lipid peroxidation level and nitrite content, as well as increased the SOD and catalase activities in rat hippocampus after seizures. Our findings strongly support the hypothesis that oxidative stress occurs in hippocampus during pilocarpine-induced seizures, indicate that brain damage induced by the oxidative process plays a crucial role in seizures pathogenic consequences, and imply that strong protective effect could be achieved using alpha-tocopherol.

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Acknowledgments

This work was supported in part by grants from the Brazilian National Research Council (CNPq), Brazil. R. M. F is fellow from CNPq. We would like to thank Stenio Gardel Maia for her technical assistance.

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Correspondence to R. M. Freitas.

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Tomé, A.R., Feng, D. & Freitas, R.M. The Effects of Alpha-Tocopherol on Hippocampal Oxidative Stress Prior to in Pilocarpine-Induced Seizures. Neurochem Res 35, 580–587 (2010). https://doi.org/10.1007/s11064-009-0102-x

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  • DOI: https://doi.org/10.1007/s11064-009-0102-x

Keywords

  • Hippocampus
  • Alpha-tocopherol
  • Oxidative stress
  • Pilocarpine
  • Seizures