Redox dyshomeostasis in the experimental chronic hepatic overloads with iron and copper

Abstract

Male rats of 80–90 g were overloaded with either Fe(II) or Cu(II) for 42 days by high concentrations of FeCl2 or CuSO4 in the drinking water. The animals were fed with a commercial rodent diet of 2780 kcal/100 g. Both metal treatments led to a liver redox imbalance and dyshomeostasis with oxidative stress and damage and the concomitant enhancement of oxidative processes as indicated by in vivo surface liver chemiluminescence, the sensitive and organ non-invasive assay for oxidative free radical reactions, and by ex vivo determined processes of phospholipid peroxidation and protein oxidation. In parallel, marked decreases in the antioxidant defense were observed. Liver reduced glutathione (GSH) content and the reduced/oxidized glutathione ratio (GSH/GSSG) were early indicators of oxidative metabolic disturbance upon the metal overloads. Thus, GSH plays a central role in the defense reactions involved in the chronic toxicity of Fe and Cu. Chronic overloads of Fe or Cu in rats afford an experimental animal model of hemochromatosis and of Wilson's disease, respectively. These two animal models could be useful in the study and development of the beneficial effects of pharmacological interventions in the two human diseases.