title: Evaluation of glutathione metabolism in NMDA preconditioning against quinolinic acid-induced seizures in mice cerebral cortex and hippocampus.
abstract: Brain preconditioning refers to a wide range of treatments that induce a neuronal tolerance state where neuronal tissue become more resistant to a subsequent lethal insult. The mechanisms underlying the preconditioning-induced brain tolerance are not fully understood, but up-regulation of antioxidant enzymes activity has been suggested to play an important role. In order to test this hypothesis, evaluation of glutathione (GSH) scavenger system was carried out in mice showing the neuroprotective effect of NMDA preconditioning against quinolinic acid (QA)-induced seizures. NMDA is known to prevent seizures in 53% of the animals and completely prevent neural damage against QA. Mice were preconditioned by a non-convulsant NMDA dose (75 mg/kg, 10 ml/kg i.p.) 24 h before QA infusion (4 microl, 9.2 mM i.c.v.). GSH content and enzymatic activities of glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST) and glucose-6-phosphate dehydrogenase (G6PDH) were evaluated in the cerebral cortex and hippocampus 24 h after QA infusion. NMDA preconditioning and QA infusion did not alter GSH content, GR and G6PDH activities, however, an increase in GST activity was observed in the cerebral cortex from mice. Moreover, NMDA pretreatment was able to prevent the QA-induced decrease in hippocampal GPx activity, but it was not effective against the decreased cortical GPx activity. These results indicate that, although NMDA preconditioning and QA toxicity modulate the activity of some GSH related enzymes, GSH metabolism is not directly linked to the neuroprotective effect induced by NMDA preconditioning.
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, 88040-900, Florianópolis, SC, Brazil.
authors.forename: Samuel
authors.initials: S
authors.lastname: Vandresen-Filho
authors.forename: Bruno
authors.initials: B
authors.lastname: de Araújo Herculano
authors.forename: Jeferson Luis
authors.initials: JL
authors.lastname: Franco
authors.forename: Carina Rodrigues
authors.initials: CR
authors.lastname: Boeck
authors.forename: Alcir Luiz
authors.initials: AL
authors.lastname: Dafre
authors.forename: Carla Inês
authors.initials: CI
authors.lastname: Tasca
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects*; D004195:Disease Models, Animal; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology*; D017378:Quinolinic Acid; D012640:Seizures / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control
chemical_list: D018690:Excitatory Amino Acid Agonists; D016202:N-Methylaspartate; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase; D017378:Quinolinic Acid; D005978:Glutathione