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

• Published in: Brain research Vol. 1334; pp. 58 - 64
• Main Authors: Safar, Marwa M, Abdallah, Dalaal M, Arafa, Nadia M, Abdel-Aziz, Mohamed T
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 02.06.2010; Elsevier
• Subjects: Amino acids; Animals; Anticonvulsants - pharmacology; Anticonvulsants - therapeutic use; Anticonvulsants. Antiepileptics. Antiparkinson agents; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Convulsions; Disease Models, Animal; Drug Synergism; gamma-Aminobutyric Acid - metabolism; Glutathione - metabolism; Lipid Peroxidation - drug effects; Magnesium; Magnesium - administration & dosage; Magnesium - blood; Magnesium - pharmacology; Male; Medical sciences; Neurology; Neuropharmacology; Nitric Oxide - metabolism; Oxidative stress; Pentylenetetrazol; Pentylenetetrazole; Pharmacology. Drug treatments; Rats; Rats, Wistar; Reaction Time - drug effects; Seizures - blood; Seizures - chemically induced; Seizures - drug therapy; Seizures - pathology; Statistics, Nonparametric; Valproate; Valproic Acid - pharmacology; Valproic Acid - therapeutic use; NO; Oxidative stress; pentylenetetrazol; antiepileptic drug; glutathione; N-methyl- d-aspartate; VPA; Amino acids; MDA; PTZ; NMDA; malondialdehyde; GSH; AED; nitric oxide; Mg 2; thiobarbituric acid reactive substances; magnesium; TBARS; valproate; total antioxidant capacity; γ-aminobutyric acid; TAC; GABA; Convulsions; Pentylenetetrazol; Valproate; Magnesium; Nervous system diseases; Pentetrazol; Rat; Rodentia; Anticonvulsant; Valproic acid; Vertebrata; Mammalia; Treatment; Convulsion; Aminoacid; Animal; Neurological disorder
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2010.03.076

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.