SUPEROXIDE RELEASE BY HUMAN POLYMORPHONUCLEAR LEUKOCYTES IN THE PRESENCE OF DEFEROXAMINE

Background and Objective. Anecdotal reports in patients with acute and chronic iron overload have recently indicated that the efficacy and s afety of an alternative chelation program including intravenous and/or continuous delivery of deferoxamine (DFO) may be in contrast with the risk of developing lung injury. Production of oxygen radicals has bee n postulated to be an important mechanism by which polymorphonuclear l eukocytes (PMNs) could cause tissue injury in patients undergoing this alternative treatment method. Methods. PMNs obtained from healthy don ors were incubated at 37 degrees C for 30 min with DFO (across the dru g concentration 0.125 to 10 mg/mL). Superoxide (O-2(-)) production was measured by superoxide inhibitable cytochrome c reduction as well as by an NBT densitometric kinetic test. In the same run the effect of li pid peroxidation was demonstrated by means of a malonyl-dialdehyde (MD A) assay. Results. Preincubation of PMNs with any study concentration of DFO significantly enhanced O-2(-) release as well as MDA production upon PMA stimulation. Maximal intracellular and extracellular O-2(-) release as well as MDA production occurred at certain drug concentrati ons. Interpretation and Conclusions. Our in vitro findings suggest tha t O-2(-) release may be an additional detrimental contribution to tiss ue injury in some patients who develop pulmonary toxic effects while o n intravenous and/or continuous DFO administration. (C) 1997, Ferrata Storti Foundation.