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Disorders of copper metabolism are associated with neurological dysfunction including Wilsons disease (WD).WD is a autosomal recessive disorder caused by mutations in the ATP7B gene resulting in the inability of the hepatocytes to remove excess copper.Gradual copper accumulation causes damage to liver, brain and other organs manifesting in liver disease, neurological and psychiatric symptoms.Alzheimers disease, Parkinsons disease and Menkes disease are all refered to some degree of copper/iron metabolism changes.The precise mechanisms by which excess copper causes neurological damage remain to be elucidated.In this study, we aims to investigate the influences of excessive amounts of Cu2+ on the oxidative damage response and survival of primary astrocytes from newborn rats.Primary cultured rat astrocytes were divided into three groups: 30 μmol/L CuCl2, 100 μmol/L CuCl2 and control.At 12, 24, 48, 96 and 120 hours of CuCl2 intervention, cell viability, intracellular reduced glutathione level and glutathion reductase activity, and nitric oxide secretion were determined.It was found that 30 μmol/L CuCl2 increased cell proliferation.The survival rate of astrocytes in the 100 μmol/L CuCl2 group was significantly decreased than in the 30 μmol/L CuCl2 group.At 24 hours of CuCl2 intervention, intracellular reduced glutathione level and glutathion reductase activity were significantly decreased in the 100 μmol/L CuCl2 group than in the control group.At 120 hours of CuCl2 intervention, nitric oxide secretion in the 100 μmol/L CuCl2 group was significantly greater than in the control group.Under pathological conditions, excessive amounts of Cu2+ greatly damaged the growth and proliferation of astrocytes, reduced the anti-oxidative capacity of astrocytes by reducing intracellular glutathione level and glutathion reductase activity, worsened oxidative stress, and activated inflammation pathway by increasing nitric oxide secretion.By the way, all these findings might provide potential molecular therapeutic targets for the neurodegenerative diseases related Cu2+ Metabolic Disorders, e.g., Wilsons disease, Parkinsons disease and Alzheimers disease.