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Neurochemical Research

, Volume 23, Issue 10, pp 1297–1302 | Cite as

Nitric Oxide Synthase Inhibition Prevents Acute Quinolinate-Induced Striatal Neurotoxicity

  • Francisca Pérez-Severiano
  • Bruno Escalante
  • Camilo Ríos
Article

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/1μl). 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.

Quinolinic acid nitric oxide lipid peroxidation neurotoxicity striatum 

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Copyright information

© Plenum Publishing Corporation 1998

Authors and Affiliations

  • Francisca Pérez-Severiano
    • 1
  • Bruno Escalante
    • 2
  • Camilo Ríos
    • 1
  1. 1.Departamento de NeuroquímicaInstituto Nacional de Neurología y Neurocirugía, Manuel Velasco SuárezSSAMéxico
  2. 2.Departamento de Farmacología y ToxicologíaCentro de Investigación y de Estudios Avanzados del IPNMéxico

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