title: The role of the glutathione system in seizures induced by diphenyl diselenide in rat pups.
abstract: The present study investigated the role of the glutathione system in seizures induced by diphenyl diselenide (PhSe)(2) (50 mg/kg) in rat pups (post natal day, 12-14). Reduced glutathione (GSH) (300 nmol/site; i.c.v.), administered 20 min before (PhSe)(2), abolished the appearance of seizures, protected against the inhibition of catalase and δ-aminolevulinic dehydratase (δ-ALA-D) activities and increased glutathione peroxidase (GPx) activity induced by (PhSe)(2). Administration of l-buthionine sulfoximine (BSO, a GSH-depleting compound) (3.2 μmol/site; i.c.v.) 24h before (PhSe)(2) increased the percentage (42-100%) of rat pups which had seizure episodes, reduced the onset for the first convulsive episode. In addition, BSO increased thiobarbituric acid reactive species (TBARS) levels and decreased GSH content, catalase, δ-ALA-D and Na(+), K(+)-ATPase activities. Treatment with sub effective doses of GSH (10 nmol/site) and d-2-amino-7-phosphonoheptanoic acid (AP-7, an antagonist of the glutamate site at the NMDA receptor; 5mg/kg, i.p.) abolished the appearance of seizures induced by (PhSe)(2) in rat pups. Sub effective doses of GSH and kynurenic acid (an antagonist of strychnine-insensitive glycine site at the NMDA receptor; 40 mg/kg, i.p.) were also able in abolishing the appearance of seizures induced by (PhSe)(2). In conclusion, administration of GSH protected against seizure episodes induced by (PhSe)(2) in rat pups by reducing oxidative stress and, at least in part, by acting as an antagonist of glutamate and glycine modulatory sites in the NMDA receptor.
authors.affiliation: Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil. marinaprigol@yahoo.com.br
authors.forename: Marina
authors.initials: M
authors.lastname: Prigol
authors.forename: César Augusto
authors.initials: CA
authors.lastname: Brüning
authors.forename: Cristina W
authors.initials: CW
authors.lastname: Nogueira
authors.forename: Gilson
authors.initials: G
authors.lastname: Zeni
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001555:Benzene Derivatives / Q000633:toxicity; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000494:pharmacology / Q000502:physiology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D007736:Kynurenic Acid / Q000494:pharmacology; D008297:Male; D016566:Organoselenium Compounds / Q000633:toxicity; D018384:Oxidative Stress; D000623:Porphobilinogen Synthase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D001555:Benzene Derivatives; D016566:Organoselenium Compounds; D016194:Receptors, N-Methyl-D-Aspartate; D017392:Thiobarbituric Acid Reactive Substances; C061132:diphenyldiselenide; D019328:Buthionine Sulfoximine; D015763:2-Amino-5-phosphonovalerate; D002374:Catalase; D005979:Glutathione Peroxidase; D000623:Porphobilinogen Synthase; D000254:Sodium-Potassium-Exchanging ATPase; D005978:Glutathione; D007736:Kynurenic Acid; C031231:2-amino-7-phosphonoheptanoic acid