Trypanosoma cruzi: Desferrioxamine decreases mortality and parasitemia in infected mice through a trypanostatic effect

• Published in: Experimental parasitology 2011-08, Vol.128 (4), p.401-408
• Main Authors: Arantes, Jerusa Marilda, Francisco, Amanda Fortes, de Abreu Vieira, Paula Melo, Silva, Maisa, Araújo, Márcio Sobreira Silva, de Carvalho, Andréa Teixeira, Pedrosa, Maria Lúcia, Carneiro, Cláudia Martins, Tafuri, Washington Luiz, Martins-Filho, Olindo Assis, Elói-Santos, Silvana Maria
• Format: Article
• Language: English
• Subjects: adverse effects; amastigotes; anemia; Animals; antioxidants; apoptosis; Biological and medical sciences; Blood Cells - drug effects; Chagas Disease - drug therapy; Chagas Disease - mortality; chelating agents; deferoxamine; Deferoxamine - pharmacology; Deferoxamine - therapeutic use; Desferrioxamine (DFO); Etiological treatment; Experimental infection; Ferritins - blood; fibroblasts; Fundamental and applied biological sciences. Psychology; growth retardation; in vivo studies; inflammation; Iron - blood; Life cycle. Host-agent relationship. Pathogenesis; Male; metabolism; Mice; mortality; oxidative stress; parasitemia; Parasitemia - drug therapy; Parasitemia - mortality; parasites; parasitology; Protozoa; protozoal infections; rapid methods; Siderophores - pharmacology; Siderophores - therapeutic use; therapeutics; Trypanocidal Agents - pharmacology; Trypanocidal Agents - therapeutic use; Trypanosoma cruzi; Trypanosoma cruzi (T. cruzi); Trypanosoma cruzi - drug effects; Trypanostatic effect; trypomastigotes; viability
• ISSN: 0014-4894; 1090-2449
• DOI: 10.1016/j.exppara.2011.05.011

[Display omitted] ► DFO (5mg/day, 35days) reduces parasitemia and early mortality in Y strain T. cruzi infected mouse. ► DFO (5mg/day, 35days) does not affect host iron metabolism and mouse blood cell counts. ► DFO decreases parasite mobility in vitro. ► DFO decreases parasite growth in fibroblast culture in vitro. ► DFO does not alter viability and does not induce significant apoptosis in vitro. 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 (5mg/animal/day) for 35days, beginning 14days 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.