Trypanosoma cruzi: desferrioxamine decreases mortality and parasitemia in infected mice through a trypanostatic effect |
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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 |
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Affiliation: | aLaboratório de Biomarcadores de Diagnóstico e Monitoração, Centro de Pesquisas René Rachou, Fundação Osvaldo Cruz, Belo Horizonte, MG, Brazil;bLaboratorio de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas (NUPEB), Instituto de Ciências Exatas e Biológicas (ICEBII), Universidade Federal de Ouro Preto (UFOP), MG, Brazil;cLaboratório 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;dDepartamento de Análises Clínicas, Escola de Farmácia, UFOP, MG, Brazil;eDepartamento de Propedêutica Complementar, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil;fPós-Graduação em Patologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil |
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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. |
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Keywords: | 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 |
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