Mild iron overload effect on rat liver nuclei

A single injection of iron-dextran significantly increased iron content in plasma, whole liver, cellular cytosol and liver nuclei. In vitro nuclear rate of Fe(3+)-EDTA reduction was not affected by the treatment. Membrane-bound enzymatic activities in the nuclei were measured after iron overload. Both NADPH- and NADH-dependent cytochrome c reductases were slightly decreased after iron overload, but cytochrome P450 was undetectable after 6 h of iron supplementation. The contents of lipid- and water-soluble antioxidants were measured in isolated nuclei from control and iron-overloaded rats. alpha-Tocopherol and beta-carotene co-elutant were decreased by 40% and 83%, respectively after 6 h of treatment. Nuclear glutathione content was not affected. The rate of generation of superoxide anion (O2-), hydrogen peroxide (H2O2) and hydroxyl radical-like species by isolated rat liver nuclei, were decreased by 50%, 40% and 60%, respectively after 6 h of iron supplementation. An identical qualitative response to iron overload was observed with NADPH and NADH. The inactivation of nuclear cytochrome P450, the significant loss in lipid-soluble antioxidants (alpha-tocopherol and beta-carotene) and the decrease in enzyme-dependent oxygen radical generation, suggest that the increase in catalytic active iron induced by iron overload could affect the cellular nuclei functionality.