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 (GalN)-sensitized mice. These protective actions of DFX correlate with an attenuated tissue damage observed in lungs, livers and kidneys of LPS-treated animals and GalN-sensitized mice inoculated with TNF-alpha.
Vulcano
M
M
División Immunologia, Instituti de Investigaciones Hematológicas Academia Nacional de Medicina, Pacheco de Melo, Buenos Aires, Argentina.
Meiss
R P
RP
Isturiz
M A
MA
D000818:Animals; D003676:Deferoxamine / Q000494:pharmacology*; D005688:Galactosamine / Q000633:toxicity; D007375:Interleukin-1 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D005688:Galactosamine; D003676:Deferoxamine