Mild iron overload effect on rat liver nuclei

Abstract

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 NADPH-dependent cytochrome c reductases were slightly decreased after iron overload, but cytochrome P 450 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. α-Tocopherol and ß-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 (O 2 −, hydrogen peroxide (H 2O 2) 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 P 450, the significant loss in lipid-soluble antioxidants (α-tocopherol and ß-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.