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Diphenyl diselenide and diphenyl ditelluride increase the latency for 4-aminopyridine-induced chemical seizure and prevent death in mice

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Brito V. B., Rocha J. B. T., Folmer V., Erthal F.

issue 1

125-134

In this work was investigated the effect of pre-treatment with (PhSe)2 and (PhTe)2 on chemical seizure and 4-aminopyridine-induced lethality in mice. Additionally, lipid peroxidation levels of whole brain after treatment with 4-aminopyridine and effect of pre-treatment with (PhSe)2 and (PhTe)2 on these levels were investigated. Mice were pre-treated with (PhSe)2 or (PhTe)2 (50, 100, or 150 µmol/kg) 30 min before 4-aminopyridine (12 mg/kg) administration. The treatment with 4-aminopyridine caused a significant incidence of seizures (clonic, tonic) and death. Pre-treatment with (PhSe)2 and (PhTe)2 significantly increased the latency for clonic and tonic seizures, and prevented 4-aminopyridine-induced death. Significantly, the pre-treatment with (PhSe)2 or (PhTe)2 increased the latency for clonic seizures in a dose-dependent manner. Additionally, a significant increase was observed in the brain lipid peroxidation level after treatment with 4-aminopyridine, which was significantly inhibited by pre-treatment with 150 µmol/kg (PhSe)2 or (PhTe)2. These results demonstrate that (PhSe)2 and (PhTe)2 counteract the harmful effects of 4-aminopyridine. It is possible that this effect results from modulation of the redox state of N-methyl-d-aspartate receptors and/or of Ca2+ channel activity with subsequent alteration in neurotransmitter release. Importantly, this study provides evidence for anticonvulsant and antioxidant properties of (PhSe)2 and (PhTe)2, which indicates a neuroprotective activity of these compounds.

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1 Acta Biochimica Polonica

1 2009

1 Brito V. B.

1 Erthal F.

1 Folmer V.

1 Rocha J. B. T.

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Diphenyl diselenide and diphenyl ditelluride increase the latency for 4-aminopyridine-induced chemical seizure and prevent death in mice