Nitric Oxide Synthase Inhibition Prevents Acute Quinolinate-Induced Striatal Neurotoxicity |
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Authors: | Pérez-Severiano Francisca Escalante Bruno Ríos Camilo |
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Affiliation: | (1) Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía, Manuel Velasco Suárez, SSA, México;(2) Departamento de Farmacología y Toxicología, Centro de Investigación y de Estudios Avanzados del IPN, México |
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Abstract: | Quinolinic acid (QUIN) is an endogenous excitotoxin acting on N-methyl-D-aspartate (NMDA) receptors, that leads to neurotoxic damage resembling the alterations observed in Huntington's disease. Two major end-points of QUIN induced neurotoxicity are both circling behavior (CB) and lipid peroxidation (LP). Recently, nitric oxide (NO) has been implicated as a mediator of cell injury in some neurological disorders, thus, NO as a free radical might be involved in QUIN-induced neurotoxicity and oxidative stress. In the present study we evaluated the possible role of NO on QUIN-induced neurotoxicity, by measuring nitric oxide synthase activity (NOS), before and after QUIN-induced damage and by evaluating the effect of NOS inhibition on acute QUIN-induced CB and LP. Rats were striatally microinjected with QUIN (240 nmol/1l). QUIN administration increased NOS activity by 327% as compared to control values and this enhancement was inhibited by i.v. pretreatment with a NOS inhibitor the NG-nitro-L-arginine methyl ester (L-NAME) (10 mg/kg). QUIN-induced CB was also attenuated by pretreatment of rats with 1, 5, 10 and 15 mg/kg of L-NAME by –37, –55, –62 and –74% vs QUIN respectively. Similarly, L-NAME also reduced by 32% the QUIN-induced LP. These findings suggest that enhanced NOS activity may participate in QUIN-induced neurotoxicity and oxidative stress. |
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Keywords: | Quinolinic acid nitric oxide lipid peroxidation neurotoxicity striatum |
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