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https://www.arca.fiocruz.br/handle/icict/2646
PUTRESCINE ANALOGUE CYTOTOXICITY AGAINST TRYPANOSOMA CRUZI
Putrescine
1,4-Diamino-2-butanone
Oxidative stress
Mitochondria
Electron microscopy
Affilliation
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz, Salvador, Bahia, Brasil
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho, Rio de Janeiro, Brasil
Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica. Rio de Janeiro, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz, Salvador, Bahia, Brasil
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho, Rio de Janeiro, Brasil
Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica. Rio de Janeiro, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz, Salvador, Bahia, Brasil
Abstract
Trypanosoma cruzi is the etiological agent of American trypanosomiasis. Most of the available data on trypanosomatid parasites were obtained from African trypanosomes. Parasitic protozoa polyamine metabolism and transport pathways comprise valuable targets for chemotherapy. T. cruzi cannot synthesize putrescine, but its uptake from the extracellular milieu can promote parasite survival. Nevertheless, little is known about the cell biology of this diamine in T. cruzi. Here we notice that the putrescine analogue 1,4-diamino-2-butanone (DAB) inhibited T. cruzi epimastigotes' in vitro proliferation and produced remarkable mitochondrial destruction and cell architecture disorganization, as assessed by transmission electron microscopy. Mitochondrial damage was confirmed by MTT reduction. We decided to analyze the oxidative stress undergone by DAB-treated parasites. Thiobarbituric-acid-reactive substances were measured to assess lipid peroxidation. Analogue effects were dose-dependent; 5 mM DAB only slightly enhanced peroxidation, whereas 10 mM DAB significantly (P < 0.05) diminished it. These data indicate that putrescine uptake by this diamine auxotrophic parasite may be important for epimastigote axenic growth and cellular organization.
Keywords
Trypanosoma cruzi .Putrescine
1,4-Diamino-2-butanone
Oxidative stress
Mitochondria
Electron microscopy
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