Papel da 5-Lipoxigenase no controle da carga parasitária e no estresse oxidaltivo de eritrócitos durante a fase aguda da infecção experimental com Trypanosoma cruzi

AUTOR(ES)

Celso Luiz Borges

DATA DE PUBLICAÇÃO

2007

RESUMO

Recently, it was demonstrated that nitric oxide (NO) produced during Trypanosoma cruzi infection participates of erythrocyte oxidative stress, but is not necessary for the development of anemia in the acute phase of infection in mice. In this work it was investigated the effect of inhibition of leukotrienes (LTs) by pharmacological or genetic blocking of the 5-lipoxygenase (5-LO) enzyme. We used C56BL/6, C57BL/6 iNOS KO, 129sv (WT) and 129 5-LO-/- T. cruzi-infected-treated or not with nordihydroguaiaretic acid (NDGA). We assessed assays to analyze anemia, the control of parasite burden, erythrocyte oxidative stress during an acute phase of T. cruzi infection. The oxidative stress in erythrocyte from mice infected-NDGA-treated or not and 5-LO-/-, was investigate by measuring oxyhaemoglobin, haemoglobin derivatives, oxygen uptake, induction time (Tind) and chemiluminescence (CL), initiated with tert-butyl hydroperoxide (t-BHT). Our data suggest that LTs does not participate in the development of the anemia during the acute phase of T. cruzi infection. We showed that the NDGA treated-infected mice lessened erythrocyte oxidative stress that grows in the sharp phase of the infection. We found that the increase of erythrocyte oxidative stress during an acute phase of T. cruzi infection. 5-LO-/- mice also presented smaller oxidative stress than control mice. The treatment with NDGA and lacking of 5-LO gene significantly increased blood and cardiac parasitism (day 12 after infection). NO production by activated macrophages was reduced so much in NDGA-treated mice as those where the 5-LO gene is absent. Our data indicate for the first time that LTs are essential in the control of load parasitic in the blood, cardiac tissue, systemic oxidative stress as well as in the regulation of the NO production by activated macrophages during the acute phase of the experimental T. cruzi infection.

ASSUNTO(S)

doença de Óxido nítrico eritrócitos experimental pathology chagas disease nitric oxide erythrocytes trypanosoma cruzi patologia experimental trypanosoma cruzi chagas

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