Presentation # 175 - Iron from parenteral preparations alters non-transferrin iron uptake and the RNA-binding activity of iron-regulatory protein in rat hepatocytes and human hepatoma cells

Standard parenteral iron preparations such as ferric sucrose and ferric gluconate are considered to be degraded in the reticuloendothelial cells. The iron is subsequently incorporated into transferrin. It was also reported that these iron preparations donate iron directly to plasma transferrin. Hepatocytes seemed unaffected. We show that this picture is incorrect. To obtain quantitative data, it was necessary to use a drastic digestion method to correctly determine the iron content of the preparations as well as of the cells. None of the preparations can donate iron to transferrin, but ferric sucrose as well as ferric gluconate donate iron to hepatocytes practically as efficiently as ferric ammonium citrate, whereas ferric dextran is completely inert. The accumulated iron cannot be released by treatment with desferrioxamine, nor with apotransferrin, in contrast to iron from ferric ammonium citrate. However, the iron with from either source lead to stimulation of non-transferrin bound iron uptake above concentrations of approximately 50μM iron. The binding activity of the iron regulatory protein to iron-responsive elements of RNA in previously iron-depleted cells is also inactivated. Polymeric iron preparations can be accumulated in hepatocytes and they are metabolically active, but not chelatable. Different pools of intracellular iron seem to cause iron stress in the cells represented by increased uptake rates for non-transferrin bound iron.