Magnesium supplementation enhances the anticonvulsant potential of valproate in pentylenetetrazol-treated rats
| Autor: | Nadia M. S. Arafa, Mohamed T. Abdel-Aziz, Marwa M. Safar, Dalaal M. Abdallah |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Taurine medicine.medical_treatment Pharmacology Nitric Oxide medicine.disease_cause Statistics Nonparametric chemistry.chemical_compound Epilepsy Seizures Reaction Time medicine Animals Magnesium Rats Wistar Pentylenetetrazol Molecular Biology gamma-Aminobutyric Acid Chemistry Valproic Acid General Neuroscience Glutamate receptor Brain Drug Synergism Glutathione medicine.disease Rats Disease Models Animal Anticonvulsant Pentylenetetrazole NMDA receptor Anticonvulsants lipids (amino acids peptides and proteins) Lipid Peroxidation Neurology (clinical) Oxidative stress Developmental Biology medicine.drug |
| Zdroj: | Brain Research. 1334:58-64 |
| ISSN: | 0006-8993 |
| DOI: | 10.1016/j.brainres.2010.03.076 |
| Popis: | N-methyl-d-aspartate (NMDA) receptor antagonists appear to enhance the anticonvulsant activity of antiepileptic drugs in several models of epilepsy. Therefore, the current study evaluates the modulatory effect of magnesium (Mg(2+)), a non-competitive NMDA receptor antagonist, on a subprotective dose of valproate (VPA) against pentylenetetrazol (PTZ)-induced convulsions. Male Wister rats received either saline or PTZ (60mg/kg, i.p.). The other three groups were pretreated with Mg(2+) (40mg/kg, p.o., 4weeks), single subprotective dose of VPA (100mg/kg, i.p.), or Mg(2+) with VPA, before PTZ injection. PTZ provoked clonic convulsions, reduced GABA content, deranged brain redox status, and elevated nitric oxide (NO). Neither the subprotective dose of VPA nor Mg(2+) alone guarded against clonic seizures invoked by PTZ, an effect that was achieved only by their combination and supported by a significant delay in seizure latency. Moreover, VPA leveled off glycine and aspartate, exerted no effect on glutamate, and unexpectedly reduced GABA and taurine levels. Mg(2+) alone or in combination showed the same pattern on the aforementioned amino acids, except for taurine. All regimens restored glutathione (GSH) and total antioxidant capacity (TAC); however, only VPA normalized NO level. This study demonstrates that Mg(2+) could enhance the antiepileptic efficacy of a subprotective dose of VPA, possibly by improving redox balance and modulation of some brain amino acids. |
| Databáze: | OpenAIRE |
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