TY - JOUR
T1 - Sub-Chronic Copper Pretreatment Reduces Oxidative Damage in an Experimental Huntington’s Disease Model
AU - Martínez-Lazcano, Juan Carlos
AU - Montes, Sergio
AU - Sánchez-Mendoza, María Alicia
AU - Rodríguez-Páez, Lorena
AU - Pérez-Neri, Iván
AU - Boll, Marie Catherine
AU - Campos-Arroyo, Hortensia Denise
AU - Ríos, Camilo
AU - Pérez-Severiano, Francisca
N1 - Publisher Copyright:
© 2014, Springer Science+Business Media New York.
PY - 2014/11/27
Y1 - 2014/11/27
N2 - 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.
AB - 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.
KW - Copper sulfate
KW - Huntington’s disease
KW - NMDA receptor
KW - Oxidative damage
KW - Quinolinic acid
KW - Superoxide dismutase
UR - http://www.scopus.com/inward/record.url?scp=84912062787&partnerID=8YFLogxK
U2 - 10.1007/s12011-014-0127-0
DO - 10.1007/s12011-014-0127-0
M3 - Artículo
C2 - 25319005
SN - 0163-4984
VL - 162
SP - 211
EP - 218
JO - Biological Trace Element Research
JF - Biological Trace Element Research
IS - 1-3
ER -