alpha-Tocopherol protects against pentylenetetrazol- and methylmalonate-induced convulsions.
Increased excitatory amino acid transmission and decreased GABAergic inhibitory responses seem to be important mechanisms in the genesis of convulsions, where reactive oxygen species (ROS) have recently been suggested to play a critical role. Therefore, administration of antioxidants may be potentially beneficial for the treatment of convulsive states. In the current study we investigated the effect of the systemic Vitamin E administration, an antioxidant, on the convulsions and oxidative damage induced by two convulsant agents with different mechanisms of action: methylmalonic acid (MMA), which induces convulsions through energy depletion and secondary activation of glutamatergic mechanisms and ROS production and pentylenetetrazol (PTZ), which is a chemical convulsant that causes convulsions by blocking the GABAA receptor-coupled chloride ionophore. Adult male Wistar rats (270-300 g) were injected with vehicle (5% Tween 80 in 0.9% NaCl; 1 ml/kg, i.p.) or alpha-tocopherol (25, 75 or 225 mg/kg, i.p.), once a day for 7 days. On the seventh day of antioxidant treatment, the animals were injected with the antioxidant (or vehicle) and, 30 min later, they were intrastriatally injected with NaCl (9 micromol/2 microl) or with MMA (6 micromol/2 microl) or PTZ (3.26 mmicromol/2 microl). The animals were observed for the appearance of convulsive behavior and the striatal content of thiobarbituric acid-reactive substances (TBARS) and total protein carbonylation were determined. Intrastriatal injection of increasing amounts of PTZ and of MMA caused the appearance of convulsive behavior. PTZ- and MMA-induced convulsions, TBARS production and total protein carbonylation were attenuated by alpha-tocopherol in a dose-dependent manner.
Ribeiro
Marinei Cristina Pereira
MC
Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil.
de Avila
Daiana Silva
DS
Schneider
Carmen Yolanda Matiauda
CY
Hermes
Fernando Stahl
FS
Furian
Ana Flávia
AF
Oliveira
Mauro Schneider
MS
Rubin
Maribel Antonello
MA
Lehmann
Martina
M
Krieglstein
Josef
J
Mello
Carlos Fernando
CF
D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007839:Functional Laterality; D008297:Male; D008764:Methylmalonic Acid; D010433:Pentylenetetrazole; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D024502:alpha-Tocopherol / Q000627:therapeutic use*
D000975:Antioxidants; D017392:Thiobarbituric Acid Reactive Substances; D008764:Methylmalonic Acid; D024502:alpha-Tocopherol; D010433:Pentylenetetrazole