Effect of chronic copper loading on the activity of rat liver antioxidative enzymes

The activity of antioxidative enzymes SOD, catalase, glutathione peroxidase and the related glutathione reductase, glucose-6-phosphate dehydrogenase and NADPH-isocitrate dehydrogenase was examined in liver cytosol and large granule fraction (mitochondria) from control and copper-loaded rats. An increase of SOD activity (more than 100%) and a decrease of both catalase (by 60%) and glutathione peroxidase activity (by 30%) in large granule fraction were observed after copper loading. The cytosolic glutathione peroxidase activity was also markedly decreased: glutathione peroxidase I (EC 1.11.1.9)--by 35% and glutathione peroxidase II (EC 2.5.1.18)--by 75%. Cytosolic catalase activity and the glutathione reductase, glucose-6-phosphate dehydrogenase and NADPH-isocitrate dehydrogenase activities in cytosol and in mitochondria of copper-loaded rats were unchanged. It is concluded that under chronic copper loading the primary mechanisms of copper toxicity are accompanied by disturbances of the antioxidative enzyme function.