title: Sub-chronic copper pretreatment reduces oxidative damage in an experimental Huntington's disease model.
abstract: Quinolinic acid (QUIN) striatal injection in rat reproduces the main neurochemical features of Huntington's disease (HD), including oxidative damage. In this study, we evaluated the effect of a copper (Cu) supplement in drinking water (90 ppm Cu, 28 days) on the QUIN-induced HD model in the rat. Copper exposure caused no signs of liver toxicity; however, it produced significant Cu accumulation in striatum. It is noteworthy that QUIN also caused increased striatal Cu content; when the supplement was administered to animals with QUIN-injury, an even higher metal striatal accumulation was observed. Cu pre-treatment preserved striatal gamma-aminobutyric acid (GABA) content, which was reduced by QUIN intrastriatal injection. Similarly, apomorphine-induced circling behavior was reduced in Cu-pretreated QUIN-damaged rats. Metal supplement in drinking water prevented both lipid peroxidation and reactive oxygen species (ROS) formation caused by QUIN in striatum. In Cu-treated groups, superoxide dismutase-1 (SOD1) activity showed a significant increase, while SOD2 activity was slightly enhanced. Although the pathophysiological role for higher Cu levels in patients with HD and in experimental models of the disease is not fully understood, results in the present study suggest that Cu oral intake stimulates anti-oxidant defenses, an effect that may be a potential factor for reducing the progression of HD.
authors.affiliation: Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez", Insurgentes Sur #3877, Col. La Fama, Del. Tlalpan, 14269, D.F., Mexico City, Mexico.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Martínez-Lazcano
authors.forename: Sergio
authors.initials: S
authors.lastname: Montes
authors.forename: María Alicia
authors.initials: MA
authors.lastname: Sánchez-Mendoza
authors.forename: Lorena
authors.initials: L
authors.lastname: Rodríguez-Páez
authors.forename: Iván
authors.initials: I
authors.lastname: Pérez-Neri
authors.forename: Marie Catherine
authors.initials: MC
authors.lastname: Boll
authors.forename: Hortensia Denise
authors.initials: HD
authors.lastname: Campos-Arroyo
authors.forename: Camilo
authors.initials: C
authors.lastname: Ríos
authors.forename: Francisca
authors.initials: F
authors.lastname: Pérez-Severiano
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000633:toxicity; D003300:Copper / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006816:Huntington Disease / Q000139:chemically induced / Q000188:drug therapy* / 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; D013482:Superoxide Dismutase / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D005680:gamma-Aminobutyric Acid; D003300:Copper; D013482:Superoxide Dismutase; D017378:Quinolinic Acid; D001058:Apomorphine