TAILIEUCHUNG - Báo cáo khoa học: Transient increase of the labile iron pool in HepG2 cells by intravenous iron preparations Brigitte Sturm, Hans Goldenberg and Barbara Scheiber-Mojdehkar

Intravenous iron, used for the treatment of anemia in chronic renal failure andother diseases, represents a possible source of free iron in tissue cells, particularly in the liver. In this study we examined the effect of different sources of intravenous iron (IVI) on the labile iron pool (LIP) which represents the nonferritin-bound, redox-active iron that is implicated in oxidative stress and cell injury. Furthermore, we examined the role of the LIP for the synthesis of ferritin. We used HepG2 cells as a well known model for hepatoma cells and monitored the LIP with the metal-sensitive fluor-escent probe, calcein-AM, the fluorescence of which is quenched on binding to iron. . | Eur. J. Biochem. 270 3731-3738 2003 FEBS 2003 doi Transient increase of the labile iron pool in HepG2 cells by intravenous iron preparations Brigitte Sturm Hans Goldenberg and Barbara Scheiber-Mojdehkar Department of Medical Chemistry University of Vienna Austria Intravenous iron used for the treatment of anemia in chronic renal failure and other diseases represents a possible source of free iron in tissue cells particularly in the liver. In this study we examined the effect of different sources of intravenous iron IVI on the labile iron pool LIP which represents the nonferritin-bound redox-active iron that is implicated in oxidative stress and cell injury. Furthermore we examined the role of the LIP for the synthesis of ferritin. We used HepG2 cells as a well known model for hepatoma cells and monitored the LIP with the metal-sensitive fluorescent probe calcein-AM the fluorescence of which is quenched on binding to iron. We showed that steady state LIP levels in HepG2 cells were increased transiently up to three-fold compared to control cells as an adaptive response to long-term IVI exposure. In relation to the amount of iron in the LIP the ferritin levels increased and the iron content of ferritin decreased. As any fluctuation in the LIP even when it is only transient . after exposure to intravenous iron in this study may result either in impairment of synthesis of iron containing proteins or in cell injury by pro-oxidants. Such findings in nonreticuloendothelial cells may have important implications in the generation of the adverse effects of chronic iron exposure reported in dialysis patients. Keywords intravenous iron labile iron pool ferritin liver protein synthesis. Parenteral iron preparations are used widely for the treatment of iron deficiency anemia in patients under chronic hemodialysis. The iron supplementation is necessary to support erythropoiesis initiated by exogenous erythropoietin 1-3 . As intestinal absorption

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