Deferoxamine reduces tissue injury and lethality in LPS-treated mice

We studied the effect of deferoxamine (DFX), an iron chelator, which can also act as a free radical scavenger, in an experimental murine model of sepsis. In vivo studies demonstrated that: pretreatment of mice with DFX reduces tumor necrosis factor alpha (TNF-alpha) serum levels and increases the rate of survival of mice inoculated with lethal doses of lipopolysaccharide (LPS) or Escherichia coli O111:B4. By using the iron chelated form of DFX (ferrioxamine) the same results were obtained, suggesting that in this model, DFX could act as a free radical scavenger. On the other hand, DFX prevents mortality induced either by LPS or murine recombinant TNF-alpha in D(+)-galactosamine (Ga1N)-sensitized mice. These protective actions of DFX correlate with an attenuated tissue damage observed in lungs, livers and kidneys of LPS-treated animals and Ga1N-sensitized mice inoculated with TNF-alpha. (C) 2000 International Society for Immunopharmacology, Published by Elsevier Science Ltd. All rights reserved.