Trypanosoma cruzi: Desferrioxamine decreases mortality and parasitemia in infected mice through a trypanostatic effect Jerusa Marilda Arantes a,f , Amanda Fortes Francisco b , Paula Melo de Abreu Vieira b , Maisa Silva c , Márcio Sobreira Silva Araújo a , Andréa Teixeira de Carvalho a , Maria Lúcia Pedrosa c , Cláudia Martins Carneiro b,d , Washington Luiz Tafuri b , Olindo Assis Martins-Filho a , Silvana Maria Elói-Santos a,e,f,⇑ a Laboratório de Biomarcadores de Diagnóstico e Monitoração, Centro de Pesquisas René Rachou, Fundação Osvaldo Cruz, Belo Horizonte, MG, Brazil b Laboratorio de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas (NUPEB), Instituto de Ciências Exatas e Biológicas (ICEBII), Universidade Federal de Ouro Preto (UFOP), MG, Brazil c Laboratório de Bioquímica e Biologia Molecular, Núcleo de Pesquisas em Ciências Biológicas (NUPEB), Instituto de Ciências Exatas e Biológicas (ICEBII), Universidade Federal de Ouro Preto (UFOP), MG, Brazil d Departamento de Análises Clínicas, Escola de Farmácia, UFOP, MG, Brazil e Departamento de Propedêutica Complementar, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil f Pós-Graduação em Patologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil article info Article history: Received 5 October 2010 Received in revised form 7 April 2011 Accepted 12 May 2011 Available online 18 May 2011 Keywords: Trypanosoma cruzi (T. cruzi) Desferrioxamine (DFO) Etiological treatment Experimental infection 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 try- pomastigotes 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. Ó 2011 Elsevier Inc. All rights reserved. 1. Introduction Desferrioxamine (DFO) is a hexadentate iron chelator that com- plexes with iron in a 1:1 M ratio to yield the stable complex fer- rioxamine (stability constant 1031). It is also known to modulate inflammation and to be an efficient antioxidant under normal con- ditions and under oxidative stress, functioning via free radical scavenging and lipid chain breaking (Minotti and Aust, 1987; Rachidi et al., 1994). The utilisation of chelators has been proposed as a strategy to disrupt the progression of a multitude of diseases, including 0014-4894/$ - see front matter Ó 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.exppara.2011.05.011 Abbreviations: d.p.i., day post-infection; i.p., intraperitoneally; PI, propidium iodide; I/T, infected/treated with DFO; I/NT, infected/non-treated with DFO; NI/T, non-infected/treated with DFO; NI/NT, non-infected/non-treated with DFO; TIBC, serum iron binding capacity; BZ, benznidazole. ⇑ Corresponding author at: Departamento de Propedêutica Complementar, Faculdade de Medicina/Universidade Federal de Minas Gerais, Avenida Professor Alfredo Balena, 190, Bairro Santa Efigênia, Belo Horizonte 30130-100, Brazil. Fax: +55 31 3409 9782. E-mail address: eloisil@medicina.ufmg.br (S.M. Elói-Santos). Experimental Parasitology 128 (2011) 401–408 Contents lists available at ScienceDirect Experimental Parasitology journal homepage: www.elsevier.com/locate/yexpr