Magnesium supplementation enhances the anticonvulsant potential of valproate in pentylenetetrazol-treated rats

Document Type

Article

Publication Date

6-2-2010

Abstract

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 (Mg2+), 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 (60 mg/kg, i.p.). The other three groups were pretreated with Mg2+ (40 mg/kg, p.o., 4 weeks), single subprotective dose of VPA (100 mg/kg, i.p.), or Mg2+ 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 Mg2+ 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. Mg2+ 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 Mg2+ could enhance the antiepileptic efficacy of a subprotective dose of VPA, possibly by improving redox balance and modulation of some brain amino acids. © 2010 Elsevier B.V. All rights reserved.

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