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Sub-Chronic Copper Pretreatment Reduces Oxidative Damage in an Experimental Huntington’s Disease Model

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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.

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Authors and Affiliations

  1. 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

    Juan Carlos Martínez-Lazcano, Sergio Montes, Iván Pérez-Neri, Marie Catherine Boll, Camilo Ríos & Francisca Pérez-Severiano

  2. Departamento de Neurofisiología, Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suárez”, Mexico City, Mexico

    Juan Carlos Martínez-Lazcano

  3. Departamento de Farmacología, Instituto Nacional de Cardiología “Ignacio Chávez”, Mexico City, Mexico

    María Alicia Sánchez-Mendoza

  4. Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas (ENCB), Instituto Politécnico Nacional (IPN), Mexico City, Mexico

    Lorena Rodríguez-Páez

  5. Laboratorio de Genómica Funcional del Cáncer, Instituto Nacional de Medicina Genómica, Mexico City, Mexico

    Hortensia Denise Campos-Arroyo

Authors
  1. Juan Carlos Martínez-Lazcano
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  2. Sergio Montes
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  5. Iván Pérez-Neri
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  6. Marie Catherine Boll
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  7. Hortensia Denise Campos-Arroyo
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  8. Camilo Ríos
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  9. Francisca Pérez-Severiano
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Corresponding author

Correspondence to Francisca Pérez-Severiano.

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Martínez-Lazcano, J.C., Montes, S., Sánchez-Mendoza, M.A. et al. Sub-Chronic Copper Pretreatment Reduces Oxidative Damage in an Experimental Huntington’s Disease Model. Biol Trace Elem Res 162, 211–218 (2014). https://doi.org/10.1007/s12011-014-0127-0

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  • DOI: https://doi.org/10.1007/s12011-014-0127-0

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