title: Copper blocks quinolinic acid neurotoxicity in rats: contribution of antioxidant systems.
abstract: Reactive oxygen species and oxidative stress are involved in quinolinic acid (QUIN)-induced neurotoxicity. QUIN, a N-methyl-D-aspartate receptor (NMDAr) agonist and prooxidant molecule, produces NMDAr overactivation, excitotoxic events, and direct reactive oxygen species formation. Copper is an essential metal exhibiting both modulatory effects on neuronal excitatory activity and antioxidant properties. To investigate whether this metal is able to counteract the neurotoxic and oxidative actions of QUIN, we administered copper (as CuSO(4)) intraperitoneally to rats (2.5, 5.0, 7.5, and 10.0 mg/kg) 30 min before the striatal infusion of 1 microliter of QUIN (240 nmol). A 5.0 mg/kg CuSO(4) dose significantly increased the copper content in the striatum, reduced the neurotoxicity measured both as circling behavior and striatal gamma-aminobutyric acid (GABA) depletion, and blocked the oxidative injury evaluated as striatal lipid peroxidation (LP). In addition, copper reduced the QUIN-induced decreased striatal activity of Cu,Zn-dependent superoxide dismutase, and increased the ferroxidase activity of ceruloplasmin in cerebrospinal fluid from QUIN-treated rats. However, copper also produced significant increases of plasma lactate dehydrogenase activity and mortality at the highest doses employed (7.5 and 10.0 mg/kg). These results show that at low doses, copper exerts a protective effect on in vivo QUIN neurotoxicity.
authors.affiliation: Laboratorio de Aminoácidos Excitadores/Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, México, D.F., Mexico.
authors.forename: Abel
authors.initials: A
authors.lastname: Santamaría
authors.forename: Abigail
authors.initials: A
authors.lastname: Flores-Escartín
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Martínez
authors.forename: Laura
authors.initials: L
authors.lastname: Osorio
authors.forename: Sonia
authors.initials: S
authors.lastname: Galván-Arzate
authors.forename: José
authors.initials: J
authors.lastname: Pedraza-Chaverrí
authors.forename: José Pedraza
authors.initials: JP
authors.lastname: Chaverrí
authors.forename: Perla D
authors.initials: PD
authors.lastname: Maldonado
authors.forename: Omar N
authors.initials: ON
authors.lastname: Medina-Campos
authors.forename: María E
authors.initials: ME
authors.lastname: Jiménez-Capdeville
authors.forename: Joaquín
authors.initials: J
authors.lastname: Manjarrez
authors.forename: Camilo
authors.initials: C
authors.lastname: Ríos
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D015153:Blotting, Western; D001835:Body Weight; D002570:Ceruloplasmin / Q000378:metabolism; D003300:Copper / Q000378:metabolism*; D019327:Copper Sulfate / Q000378:metabolism; D005609:Free Radicals; D007477:Ions; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D018384:Oxidative Stress; D017378:Quinolinic Acid / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005609:Free Radicals; D007477:Ions; D017382:Reactive Oxygen Species; D016194:Receptors, N-Methyl-D-Aspartate; D005680:gamma-Aminobutyric Acid; D003300:Copper; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D002570:Ceruloplasmin; D017378:Quinolinic Acid; D019327:Copper Sulfate