Quinolinic acid induces oxidative stress in rat brain synaptosomes.
The oxidative action of quinolinic acid (QUIN), and the protective effects of glutathione (GSH), and 2-amino-5-phosphonovaleric acid (APV), were tested in rat brain synaptosomes, Reactive oxygen species (ROS) formation was quantified after the exposure of synaptosomes to increasing concentrations of QUIN (25-500 microM). The potency of QUIN to induce lipid peroxidation (LP) was tested as a regional index of thiobarbituric acid-reactive substances (TBARS) production, and the antioxidant actions of both GSH (50 microM) and APV (250 microM) on QUIN-induced LP were evaluated in synaptosomes prepared from different brain regions. QUIN induced concentration-dependent increases in ROS formation and TBARS in all regions analyzed, but increased production of fluorescent peroxidized lipids only in the striatum and the hippocampus, whereas both GSH and APV decreased this index. These results suggest that the excitotoxic action of QUIN involves regional selectivity in the oxidative status of brain synaptosomes, and may be prevented by substances exhibiting antagonism at the NMDA receptor.
Department of Neurochemistry, National Institute of Neurology and Neurosurgery Manuel Velasco Suárez SSA, Insurgentes Sur, Mexico DF, Mexico.
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Santamaría
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Galván-Arzate
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Lisý
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Ali
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Duhart
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Osorio-Rico
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Ríos
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St'astný
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism; D018728:Entorhinal Cortex / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D017378:Quinolinic Acid / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D017382:Reactive Oxygen Species; D015763:2-Amino-5-phosphonovalerate; D017378:Quinolinic Acid