MILD IRON OVERLOAD EFFECT ON RAT-LIVER NUCLEI

A single injection of iron-dextran significantly increased iron conten t in plasma, whole liver, cellular cytosol and liver nuclei. In vitro nuclear rate of Fe3+-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 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. alpha-Tocopherol and beta-carotene co-elutant were decreased by 40% and 83%, respectively after 6 h of tr eatment. Nuclear glutathione content was not affected. The rate of gen eration of superoxide anion (O-2(-)), hydrogen peroxide (H2O2) and hyd roxyl radical-like species by isolated rat liver nuclei, were decrease d 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 sign ificant loss in lipid-soluble antioxidants (alpha-tocopherol and beta- carotene) and the decrease in enzyme-dependent oxygen radical generati on, suggest that the increase in catalytic active iron induced by iron overload could affect the cellular nuclei functionality.