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

被引:15
作者
Arantes, Jerusa Marilda [2 ]
Francisco, Amanda Fortes [3 ]
de Abreu Vieira, Paula Melo [3 ]
Silva, Maisa [4 ]
Silva Araujo, Mardi Sobreira [2 ]
de Carvalho, Andrea Teixeira [2 ]
Pedrosa, Maria Lucia [4 ]
Carneiro, Claudia Martins [3 ,5 ]
Tafuri, Washington Luiz [3 ]
Martins-Filho, Olindo Assis [2 ]
Eloi-Santos, Silvana Maria [1 ,2 ]
机构
[1] Univ Fed Minas Gerais, Fac Med, Dept Propedeut Complementar, BR-30130100 Belo Horizonte, MG, Brazil
[2] Fundacao Osvaldo Cruz, Ctr Pesquisas Rene Rachou, Lab Biomarcadores Diagnost & Monitoracao, Belo Horizonte, MG, Brazil
[3] Univ Fed Ouro Preto UFOP, Inst Ciencias Exatas & Biol ICEBII, Nucleo Pesquisas Ciencias Biol NUPEB, Lab Imunopatol, Ouro Preto, MG, Brazil
[4] Univ Fed Ouro Preto UFOP, Inst Ciencias Exatas & Biol ICEBII, Nucleo Pesquisas Ciencias Biol NUPEB, Lab Bioquim & Biol Mol, Ouro Preto, MG, Brazil
[5] Univ Fed Ouro Preto, Escola Farm, Dept Anal Clin, Ouro Preto, MG, Brazil
关键词
Trypanosoma cruzi (T. cruzi); Desferrioxamine (DFO); Etiological treatment; Experimental infection; Trypanostatic effect; IRON CHELATOR DESFERRIOXAMINE; BLOOD-STREAM FORMS; IN-VITRO; INHIBITION; INVASION; PERSPECTIVES; STRAINS; FUSION; GROWTH; DRUGS;
D O I
10.1016/j.exppara.2011.05.011
中图分类号
R38 [医学寄生虫学]; Q [生物科学];
学科分类号
07 ; 0710 ; 09 ; 100103 ;
摘要
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. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码:401 / 408
页数:8
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