Efeitos da desferrioxamina sobre aspectos parasitológicos, bioquímicos e imunológicos durante o curso da infecção aguda pelo Trypanosoma cruzi em camundongos

AUTOR(ES)
FONTE

IBICT - Instituto Brasileiro de Informação em Ciência e Tecnologia

DATA DE PUBLICAÇÃO

04/03/2011

RESUMO

Desferrioxamine (DFA) 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 DFA in the treatment of viral, bacterial and protozoan infections. DFA 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 DFA on mouse T. cruzi infection outcomes and the supposed direct impact of DFA on parasites. Infected animals treated with DFA (5 mg/animal/day) for 35 days, beginning 14 days prior to infection, presented lower parasitemia and lower cumulative mortality rate. Also in the rapid test in vivo, DFA was able to reduce parasitemia. No significant effect was observed on iron metabolism markers, erythrograms, leukograms. The treatment regimen of DFA, in the presence of infection or not, did not alter the percentage of NK+, CD19+, CD4+ or CD8+ spleen cells, but in the presence of infection, stimulated the production of TNF-a by NK cells and IL-10 by NK cells and CD4+, featuring a mixed effect which combines inflammatory and anti-inflamatory properties. In relation to its direct impact on parasites, DFA inhibited the growth of amastigotes and trypomastigotes in fibroblast culture and decreased in parasite mobility. The DFA did not affect the viability assessed by trypan blue and induced discrete apoptosis in trypomastigotes. In conclusion, the therapeutic effect of DFA in the experimental T. cruzi infection involves parasitological mechanisms preferably trypanostatic and systemic mechanisms, by inducing a cytokine environment favorable to host and it is independent of the installation of iron deficiency and thus free of signicant hematological effects

ASSUNTO(S)

desferroxamina/farmacologia decs desferroxamina/uso terapêutico decs infecção decs doença de chagas decs trypanosoma cruzi/efeito de drogas decs camundongos decs avaliação de medicamentos decs dissertações acadêmicas decs dissertação da faculdade de medicina da ufmg.

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