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Ascorbate modulates pentylenetetrazol-induced convulsions biphasically.

Abstract：

:Ascorbate is an antioxidant vitamin that is found in high concentrations in the brain which seems to have neuroprotective properties in some experimental models of excitotoxic neurological disorders, including convulsive behavior and reactive species-related damage. In this study we tested whether ascorbate (30, 100 or 300 mg/kg, i.p.) protects against the convulsions, protein carbonylation and inhibition of Na(+),K(+)-ATPase activity induced by pentylenetetrazol (PTZ; 1.8 micromol/striatum), a classical convulsant agent that has been fairly used for the study of epilepsy and screening of new compounds with antiepileptic activity. The intrastriatal injection of PTZ caused convulsive behavior in a dose-dependent manner and an increase in the total protein carbonyl content of the injected striatum. However, duration of PTZ-induced convulsive episodes did not correlate with protein carbonyl content of the injected striatum. Ascorbate, at high doses (300 mg/kg), protected against PTZ-induced convulsions, protein carbonylation and inhibition of Na(+),K(+)-ATPase activity in the rat striatum, further suggesting a anticonvulsant and neuroprotective role for this vitamin. Conversely, intermediate doses of ascorbate (100 mg/kg) potentiated the duration of the convulsive episodes, but had no additive effects on protein carbonylation or Na(+),K(+)-ATPase activity inhibition induced by PTZ. Low doses of ascorbate (30 mg/kg) prevented PTZ-induced increase of total striatal carbonyl protein content, but did not alter PTZ-induced convulsions and Na(+),K(+)-ATPase activity inhibition. Collectively, these data indicate that the anticonvulsant activity of ascorbate is not related to its antioxidant action and support a dual role for this compound as a neuroprotective agent, since while it protects against PTZ-induced cellular oxidative damage, it has a biphasic effect on PTZ-induced convulsions.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Schneider Oliveira M,Flávia Furian A,Freire Royes LF,Rechia Fighera M,de Carvalho Myskiw J,Gindri Fiorenza N,Mello CF

doi

10.1016/j.neuroscience.2004.07.012

keywords:

subject

Has Abstract

pub_date

2004-01-01 00:00:00

pages

721-8

issue

eissn

0306-4522

issn

1873-7544

pii

S0306-4522(04)00607-4

journal_volume

128

pub_type

杂志文章

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Ascorbate modulates pentylenetetrazol-induced convulsions biphasically.