In vivo hydroxyl radical formation after quinolinic acid infusion into rat corpus striatum.
We studied the effect of an acute infusion of quinolinic acid (QUIN) on in vivo hydroxyl radical (.OH) formation in the striatum of awake rats. Using the microdialysis technique, the generation of.OH was assessed through electrochemical detection of the salicylate hydroxylation product 2,3-dihydroxybenzoic acid (2,3-DHBA). The .OH extracellular levels increased up to 30 times over basal levels after QUIN infusion (240 nmol/microl), returning to the baseline 2 h later. This response was attenuated, but not abolished, by pretreatment with the NMDA receptor antagonist MK-801 (10 mg/kg, i.p.) 60 min before QUIN infusion. The mitochondrial toxin 3-nitropropionic acid (3-NPA, 500 nmol/microl) had stronger effects than QUIN on .OH generation, as well as on other markers of oxidative stress explored as potential consequences of .OH increased levels. These results support the hypothesis that early .OH generation contributes to the pattern of toxicity elicited by QUIN. The partial protection by MK-801 suggests that QUIN neurotoxicity is not completely explained through NMDA receptor overactivation, but it may also involve intrinsic QUIN oxidative properties.
Santamaría
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A
Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, SSA. Av. Insurgentes Sur 3877, México D.F. 14269, Mexico.
Jiménez-Capdeville
M E
ME
Camacho
A
A
Rodríguez-Martínez
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E
Flores
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A
Galván-Arzate
S
S
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D062385:Hydroxybenzoates / Q000032:analysis / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D017551:Microdialysis; D008845:Microinjections; D018696:Neuroprotective Agents / Q000494:pharmacology; D009574:Nitro Compounds; D018384:Oxidative Stress; D010477:Perfusion; D011422:Propionates / Q000008:administration & dosage; D017378:Quinolinic Acid / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D020156:Salicylic Acid / Q000008:administration & dosage / Q000378:metabolism; D014851:Wakefulness
D018691:Excitatory Amino Acid Antagonists; D062385:Hydroxybenzoates; D018696:Neuroprotective Agents; D009574:Nitro Compounds; D011422:Propionates; D017665:Hydroxyl Radical; D016291:Dizocilpine Maleate; C009135:2,3-dihydroxybenzoic acid; D005979:Glutathione Peroxidase; D017378:Quinolinic Acid; D005978:Glutathione; D020156:Salicylic Acid; C015392:3-nitropropionic acid