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: Marina Prigol, César Augusto Brüning, Cristina W Nogueira, Gilson Zeni
• Journal: Chemico-biological interactions (Chem Biol Interact) Vol. 193 Issue 1 Pg. 65-70 (Aug 15 2011) ISSN: 1872-7786 [Electronic] Ireland
• PMID: 21620807 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011. Published by Elsevier Ireland Ltd.

Chemical References

• Benzene Derivatives
• Organoselenium Compounds
• Receptors, N-Methyl-D-Aspartate
• Thiobarbituric Acid Reactive Substances
• diphenyldiselenide
• Buthionine Sulfoximine
• 2-Amino-5-phosphonovalerate
• Catalase
• Glutathione Peroxidase
• Porphobilinogen Synthase
• Sodium-Potassium-Exchanging ATPase
• Glutathione
• Kynurenic Acid
• 2-amino-7-phosphonoheptanoic acid

Topics

• 2-Amino-5-phosphonovalerate (analogs & derivatives, pharmacology)
• Animals
• Animals, Newborn
• Benzene Derivatives (toxicity)
• Buthionine Sulfoximine (pharmacology)
• Catalase (metabolism)
• Female
• Glutathione (pharmacology, physiology)
• Glutathione Peroxidase (metabolism)
• Kynurenic Acid (pharmacology)
• Male
• Organoselenium Compounds (toxicity)
• Oxidative Stress
• Porphobilinogen Synthase (metabolism)
• Rats
• Rats, Wistar
• Receptors, N-Methyl-D-Aspartate (agonists, antagonists & inhibitors, metabolism)
• Seizures (chemically induced)
• Sodium-Potassium-Exchanging ATPase (metabolism)
• Thiobarbituric Acid Reactive Substances (metabolism)