The aims of the present study were to investigate the possible involvement of glutamatergic system in
seizures induced by
diphenyl diselenide in rat pups (postnatal day, 12-14) and to evaluate the role of oxidative stress in
seizures induced by
diphenyl diselenide/
glutamate.
Glutamate (4 g/kg of
body weight) administered in association with
diphenyl diselenide (500 mg/kg of
body weight) increased the latency for the appearance of the first seizure episode, reduced lipid peroxidation levels and
catalase, Na+,K+-
ATPase and delta-ALA-D activities. At the lowest dose (5 mg/kg of
body weight),
diphenyl diselenide reduced the appearance of seizure episodes induced by
glutamate but did not alter the latency for the onset of the first episode.
Glutamate uptake was inhibited in
glutamate,
diphenyl diselenide (the highest dose) and in the association of
diphenyl diselenide (both doses) and
glutamate groups. Pre-treatment with a
N-methyl-D-aspartate (
NMDA) receptor antagonist,
MK-801 (5S,10R-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-
imine maleate), significantly prolonged the latency for the onset for the first convulsive episode. A non-
NMDA receptor antagonist,
DNQX (6,7-dinitroquinoxaline-2,3-dione), did not protect
seizures induced by
diphenyl diselenide. The results of the present study demonstrated that: (a) when
diphenyl diselenide and
glutamate were administered concomitantly in pups,
glutamate was the main responsible for the neurotoxic effects; (b) oxidative stress was not involved in
glutamate-induced
seizures; (c)
NMDA glutamatergic receptors, were at least in part, involved in
diphenyl diselenide- induced
seizures; and (d)
diphenyl diselenide, at the lowest dose, protected
seizures induced by
glutamate.