In vitro study on the effects of iron sucrose, ferric gluconate and iron dextran on redox-active iron and oxidative stress.
Concerns exist that administration of intravenous (i.v.) iron preparations is associated with oxidative stress. Therefore iron sucrose (CAS 8047-67-4), ferric gluconate (CAS 34098-81-1) and iron dextran (CAS 9004-66-4) were assessed for redox-active iron by a dichlorofluorescein assay and for intracellular reactive oxygen species (ROS) generation and cytotoxicity in HepG2 cells. Examining each i.v. iron preparation at its maximum concentration achieved following clinically frequently used doses in a 70 kg individual in in vitro experiments, redox-active iron was highest with ferric gluconate, followed by iron dextran and iron sucrose. Interestingly, when the i.v. iron preparations were diluted in human serum instead of buffer, redox-active iron was highest with iron dextran, followed by iron sucrose, and practically disappeared with ferric gluconate. ROS production in HepG2 cells was increased by all i.v. iron preparations. However, in the neutral red cytotoxicity assay all i.v. iron preparations were non-toxic. In conclusion, ferric gluconate showed the highest increase in intracellular ROS-production in HepG2 cells and the highest amount of redox-active iron in buffer in the in vitro assays. In contrast to the other i.v. iron preparations, redox-active iron from ferric gluconate was rendered completely redox-inactive by serum, indicating that redox-active iron in the various preparations has different chemical properties.
Sturm
Brigitte
B
Department of Medical Chemistry, Medical University of Vienna, Austria.
Steinkellner
Hannes
H
Ternes
Nina
N
Goldenberg
Hans
H
Scheiber-Mojdehkar
Barbara
B
D002470:Cell Survival / Q000187:drug effects; D003911:Dextrans / Q000494:pharmacology*; D005290:Ferric Compounds / Q000494:pharmacology*; D000077605:Ferric Oxide, Saccharated; D016166:Free Radical Scavengers / Q000494:pharmacology; D005937:Glucaric Acid; D056945:Hep G2 Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007501:Iron / Q000097:blood*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism
D003911:Dextrans; D005290:Ferric Compounds; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D007501:Iron; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid; C035552:ferric gluconate