Superoxide release by human polymorphonuclear leukocytes in the presence of deferoxamine

Abstract

BACKGROUND AND OBJECTIVE: Anecdotal reports in patients with acute and chronic iron overload have recently indicated that the efficacy and safety 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 been postulated to be an important mechanism by which polymorphonuclear leukocytes (PMNs) could cause tissue injury in patients undergoing this alternative treatment method. METHODS: PMNs obtained from healthy donors were incubated at 37 degrees C for 30 min with DFO (across the drug concentration 0.125 to 10 mg/mL). Superoxide (O2) 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 lipid peroxidation was demonstrated by means of a malonyl-dialdehyde (MDA) assay. RESULTS: Preincubation of PMNs with any study concentration of DFO significantly enhanced O2 release as well as MDA production upon PMA stimulation. Maximal intracellular and extracellular O2-release as well as MDA production occurred at certain drug concentrations. INTERPRETATION AND CONCLUSIONS: Our in vitro findings suggest that O2-release may be an additional detrimental contribution to tissue injury in some patients who develop pulmonary toxic effects while on intravenous and/or continuous DFO administration.