title: Effects of deferoxamine, feroxamine and iron on experimental mucormycosis (zygomycosis).
abstract: Mucormycosis was induced in healthy guinea pigs by the i.v. injection of spores from Rhizopus microsporus var. rhizopodiformis or from Rhizopus oryzae, leading to a reproducible mortality. Pretreatment with one dose of 50 mg of deferoxamine (DFO) shortened animal survival from 4.2 +/- 0.4 to 3.3 +/- 0.5 days for Rh. rhizopodiformis and from 8.8 +/- 0.4 to 7.3 +/- 1.9 days for Rh. oryzae (P less than 0.05). Survival was shortened even more after 4 doses of DFO (P = 0.0013 for Rh. rhizopodiformis and P = 0.002 for Rh. oryzae). After Rh. oryzae infection, animal survival decreased similarly after DFO, feroxamine or DFO combined with Fe3+ citrate (P less than 0.001). Fe3+ citrate also decreased survival (P = 0.0011), although significantly less than DFO either alone or combined with Fe3+. In vitro growth of both fungal strains was enhanced by addition of either DFO or Fe3+ at 0.001 to 1 mmol in the medium. DFO abolished the prolonged survival induced by amphotericin B in vivo and in vitro. Indeed, four doses of DFO abolished the improved survival due to amphotericin B (P = 0.0019 for Rh. rhizopodiformis and P = 0.002 for Rh. oryzae); DFO combined with Fe3+ at greater than or equal to 0.1 mmol decreased the antifungal activity of amphotericin B in vitro. These results point to a major role of DFO in the pathogenesis of mucormycosis in dialysis patients and suggest that DFO behaves as a siderophore for Rhizopus strains, stimulating their growth.
authors.affiliation: Department of Bacteriology and Mycology, Janssen Research Foundation, Beerse, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Van Cutsem
authors.forename: J R
authors.initials: JR
authors.lastname: Boelaert
mesh_terms: D000666:Amphotericin B / Q000627:therapeutic use; D000818:Animals; D003676:Deferoxamine / Q000494:pharmacology*; D005290:Ferric Compounds / Q000494:pharmacology*; D006168:Guinea Pigs; D007501:Iron / Q000494:pharmacology*; D007502:Iron Chelating Agents / Q000494:pharmacology*; D008297:Male; D009091:Mucormycosis / Q000188:drug therapy / Q000209:etiology*; D012233:Rhizopus / Q000187:drug effects / Q000254:growth & development; D013268:Stimulation, Chemical
chemical_list: D005290:Ferric Compounds; D007502:Iron Chelating Agents; C002577:ferrioxamine B; C025314:ferric citrate; D000666:Amphotericin B; D007501:Iron; D003676:Deferoxamine