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Ascorbate modulates pentylenetetrazol-induced convulsions biphasically.
M Schneider Oliveira1, A Flávia Furian, L F Freire Royes
1Department of Physiology, Center of Health Sciences, Federal University of Santa Maria, 97105-900 Santa Maria, RS, Brazil.
Neuroscience
|October 7, 2004
Summary
High-dose ascorbate (vitamin C) shows anticonvulsant and neuroprotective effects against pentylenetetrazol-induced seizures in rats. However, its anticonvulsant activity is not linked to its antioxidant properties, suggesting a complex role in neuroprotection.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Ascorbate (vitamin C) is a brain antioxidant with potential neuroprotective effects.
- Excitotoxic neurological disorders, like epilepsy, involve convulsive behavior and oxidative stress.
- Pentylenetetrazol (PTZ) is a standard agent for studying epilepsy and screening anticonvulsants.
Purpose of the Study:
- To investigate the neuroprotective and anticonvulsant effects of ascorbate against PTZ-induced seizures in rats.
- To determine if ascorbate's anticonvulsant activity correlates with its antioxidant effects on protein carbonylation and Na(+),K(+)-ATPase activity.
Main Methods:
- Rats received intrastriatal injections of PTZ (1.8 micromol/striatum) to induce seizures.
- Varying doses of ascorbate (30, 100, 300 mg/kg, i.p.) were administered.
- Evaluated were convulsive behavior, protein carbonylation, and Na(+),K(+)-ATPase activity in the striatum.
Main Results:
- PTZ induced dose-dependent convulsions and increased protein carbonylation and inhibited Na(+),K(+)-ATPase activity.
- High-dose ascorbate (300 mg/kg) significantly reduced PTZ-induced convulsions, protein carbonylation, and Na(+),K(+)-ATPase inhibition.
- Intermediate doses (100 mg/kg) prolonged convulsions without affecting oxidative stress markers, while low doses (30 mg/kg) reduced protein carbonylation but not convulsions.
Conclusions:
- Ascorbate exhibits a dual role in PTZ-induced seizures, acting as a neuroprotective agent against oxidative damage.
- The anticonvulsant effect of ascorbate is independent of its antioxidant action.
- Ascorbate demonstrates a biphasic effect on seizure duration, highlighting its complex neuropharmacological profile.