Diphenyl diselenide-induced seizures in rat pups: possible interaction with glutamatergic system.
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.
Prigol
Marina
M
Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil.
Wilhelm
Ethel A
EA
Stangherlin
Eluza C
EC
Barancelli
Daniela A
DA
Nogueira
Cristina W
CW
Zeni
Gilson
G
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001555:Benzene Derivatives / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D015227:Lipid Peroxidation; D016566:Organoselenium Compounds / Q000494:pharmacology*; D000623:Porphobilinogen Synthase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000975:Antioxidants; D001555:Benzene Derivatives; D016566:Organoselenium Compounds; D017392:Thiobarbituric Acid Reactive Substances; C061132:diphenyldiselenide; D018698:Glutamic Acid; D000623:Porphobilinogen Synthase; D000254:Sodium-Potassium-Exchanging ATPase