Ebselen blocks the quinolinic acid-induced production of thiobarbituric acid reactive species but does not prevent the behavioral alterations produced by intra-striatal quinolinic acid administration in the rat.
Ebselen (EBS) is a seleno-organic compound with glutathione peroxidase-like activity which is neuroprotective in acute stroke ischemia. In this study, we investigated the effect of EBS on quinolinic acid (QA)-induced neurotoxicity. EBS inhibited QA-induced production of thiobarbituric acid reactive species (TBARS) by striatal homogenates in vitro with an IC(50) of 1.85 microM. Intra-striatal injection of QA (360 nmol) increased striatal content of TBARS and induced convulsions and contralateral rotational behavior. Intra-striatal pre-injection of EBS (10 nmol) 15 min before QA abolished QA-induced TBARS production but did not alter QA-induced behavioral effects. The present findings suggest that EBS acts on post-receptor events, neutralizing free radicals produced by overstimulation of N-methyl-D-aspartate receptors.
Rossato
Janine I
JI
Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, 97105-900, RS, Santa Maria, Brazil.
Zeni
Gilson
G
Mello
Carlos F
CF
Rubin
Maribel A
MA
Rocha
João B T
JB
D000818:Animals; D001393:Azoles / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004347:Drug Interactions / Q000502:physiology; D006120:Grooming / Q000187:drug effects / Q000502:physiology; D054833:Isoindoles; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016566:Organoselenium Compounds / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D017378:Quinolinic Acid / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D001393:Azoles; D054833:Isoindoles; D018696:Neuroprotective Agents; D016566:Organoselenium Compounds; D017382:Reactive Oxygen Species; D016194:Receptors, N-Methyl-D-Aspartate; D017392:Thiobarbituric Acid Reactive Substances; C042986:ebselen; D017378:Quinolinic Acid