CONICET | Buscador de Institutos y Recursos Humanos

Objectives: Copper (Cu) is widely used in industry for the manufacture of a vast range of goodsincluding Cu-intrauterine devices (IUDs), electronic products, agrochemicals, and many others. It isalso one of the trace elements essential to human health in the right measure and is used as aparenteral supplement in patients unable to ingest food. Elevated Cu levels have been found in theplasma of women using Cu-IUDs and in farmers working with Cu-based pesticides. However,possible alterations due to Cu overload in the brain have been poorly studied. Therefore, the aim ofthis study was to investigate the effects of Cu administration on rat brain in Cu-sufficient and Cudeficientanimals fed on semi-synthetic diets with different doses of Cu (7 or 35 ppm).Methods: We aimed to investigate the effects of Cu administration using two routes of administration:oral and intraperitoneal (IP). Male Wistar rats were feeding (one month) a complete (7ppm) or a deficient (traces) Cu diets subdivided into three categories oral-, intraperitoneal- (orboth) supplemented with copper carbonate (7 to 35 ppm). Cu content in plasma, brain zones(cortex and hippocampus), antioxidant enzyme activities, and protease systems involved in programmedcell death were determined.Results: The results show that Cu levels and the concentration of Cu in plasma and brain were dosedependentand administration route-dependent and demonstrated a prooxidative effect in plasmaand brain homogenates. Oxidative stress biomarkers and antioxidative enzyme activity bothincreased under Cu overload, these effects being more noticeable when Cu was administered IP.Concomitantly, brain lipids from cortex and hippocampus were strongly modified, reflecting Cuinducedprooxidative damage. A significant increase in the activities of calpain (milli- and micro-)and caspase-3 activity also was observed as a function of dose and administration route.Conclusion: The findings of this study could be important in evaluating the role of Cu in brainmetabolism and neuronal survival.