title: Trypanosoma cruzi: desferrioxamine decreases mortality and parasitemia in infected mice through a trypanostatic effect.
abstract: Desferrioxamine (DFO) is a potent iron chelator that is also known to modulate inflammation and act as an efficient antioxidant under normal conditions and under oxidative stress. Many in vitro and in vivo studies have shown the efficacy of DFO in the treatment of viral, bacterial and protozoan infections. DFO is known to reduce the intensity of Trypanosoma cruzi infections in mice even during a course of therapy that is not effective in maintaining anaemia or low iron levels. To further clarify these findings, we investigated the action of DFO on mouse T. cruzi infection outcomes and the direct impact of DFO on parasites. Infected animals treated with DFO (5 mg/animal/day) for 35 days, beginning 14 days prior to infection, presented lower parasitemia and lower cumulative mortality rate. No significant effect was observed on iron metabolism markers, erythrograms, leukograms or lymphocyte subsets. In the rapid method for testing in vivo T. cruzi susceptibility, DFO also induced lower parasitemia. In regard to its direct impact on parasites, DFO slightly inhibited the growth of amastigotes and trypomastigotes in fibroblast culture. Trypan blue staining showed no effects of DFO on parasite viability, and only minor apoptosis in trypomastigotes was observed. Nevertheless, a clear decrease in parasite mobility was detected. In conclusion, the beneficial actions of DFO on mice T. cruzi infection seem to be independent of host iron metabolism and free of significant haematological side effects. Through direct action on the parasite, DFO has more effective trypanostatic than trypanocidal properties.
authors.affiliation: Laboratório de Biomarcadores de Diagnóstico e Monitoração, Centro de Pesquisas René Rachou, Fundação Osvaldo Cruz, Belo Horizonte, MG, Brazil.
authors.forename: Jerusa Marilda
authors.initials: JM
authors.lastname: Arantes
authors.forename: Amanda Fortes
authors.initials: AF
authors.lastname: Francisco
authors.forename: Paula Melo
authors.initials: PM
authors.lastname: de Abreu Vieira
authors.forename: Maisa
authors.initials: M
authors.lastname: Silva
authors.forename: Márcio Sobreira Silva
authors.initials: MS
authors.lastname: Araújo
authors.forename: Andréa Teixeira
authors.initials: AT
authors.lastname: de Carvalho
authors.forename: Maria Lúcia
authors.initials: ML
authors.lastname: Pedrosa
authors.forename: Cláudia Martins
authors.initials: CM
authors.lastname: Carneiro
authors.forename: Washington Luiz
authors.initials: WL
authors.lastname: Tafuri
authors.forename: Olindo Assis
authors.initials: OA
authors.lastname: Martins-Filho
authors.forename: Silvana Maria
authors.initials: SM
authors.lastname: Elói-Santos
mesh_terms: D000818:Animals; D001773:Blood Cells / Q000187:drug effects; D014355:Chagas Disease / Q000188:drug therapy* / Q000401:mortality; D003676:Deferoxamine / Q000494:pharmacology / Q000627:therapeutic use*; D005293:Ferritins / Q000097:blood; D007501:Iron / Q000097:blood; D008297:Male; D051379:Mice; D018512:Parasitemia / Q000188:drug therapy* / Q000401:mortality; D017262:Siderophores / Q000494:pharmacology / Q000627:therapeutic use; D014344:Trypanocidal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D017262:Siderophores; D014344:Trypanocidal Agents; D005293:Ferritins; D007501:Iron; D003676:Deferoxamine