Resposta parasitol?gicas e inflamat?ria de diferentes doses da Nitazoxanida na infec??o aguda em camundongos C57BL/6 infectados pela cepa Y do Trypanosoma cruzi.

Programa de P?s-Gradua??o em Ci?ncias Biol?gicas. N?cleo de Pesquisas em Ci?ncias Biol?gicas, Pr?-Reitoria de Pesquisa de P?s Gradua??o, Universidade Federal de Ouro Preto.Descoberta h? mais de 100 anos, a infec??o pelo Trypanossoma cruzi ainda demanda de uma estrat?gia terap?utica eficaz. O f?rmaco Benznidazol atua sobre o controle parasit?rio e regula??o da resposta imune em fase aguda, mas apresenta resultados insatisfat?rios em fase cr?nica com alta toxicidade e efeitos diversos, o que acarreta no abandono terap?utico. Por essa raz?o, novas estrat?gias farmacol?gicas t?m sido propostas visando a elimina??o dos parasitos e a regula??o da resposta inflamat?ria, elementos chaves para a patog?nese card?aca associada a este protozo?rio. Dentre as novas estrat?gias, destaca-se o f?rmaco Nitazoxanida (NTZ) com atividade anti-viral, anti-helm?ntica e anti-protozo?rio. Neste estudo, diferentes doses de NTZ (100, 200, 400, 600, 800, 1000 e 1200 mg / kg) foram administradas, via gavagem, durante 10 dias (12 em 12 horas) em camundongos C57BL/6 (n=9) infectados com 4.000 formas tripomastigotas do T. cruzi (cepa Y), al?m dos grupos: infectados n?o tratados e n?o infectados n?o tratados. A parasitemia foi realizada diariamente e, ap?s a eutan?sia (11? dia de infec??o), amostras de macerado card?aco e de plasma foram destinadas a an?lise de mediadores inflamat?rios (TNF, IL-10, IL-17 e CCL2) e bioqu?mica (TGO e TGP). Foi observado aumento no pico de parasitemia em todos os animais infectados e tratados com NTZ. N?o houve altera??o na massa card?aca ap?s o tratamento com NTZ, por?m observou-se 40% de mortalidade nos animais tratados com a dose de 1.200 mg/kg deste f?rmaco. A produ??o de TNF, CCL2 e IL-10 reduziu nos grupos tratados com NTZ em rela??o ao grupo n?o infectado e sem tratamento. Relativo ? produ??o de IL-17, houve redu??o nos animais tratados com NTZ em rela??o ao grupo infectado, por?m n?o tratado. N?o houve altera??o de TGP associada ? infec??o e ao tratamento, por?m detectou-se n?veis elevados de TGO com as doses de 800, 1000 e 1200 mg/kg de NTZ. Conclu?mos que doses menores de NTZ apresentaram regula??o parcial dos mediadores inflamat?rios (TNF, IL-10, IL-17 e CCL2) na fase aguda em camundongos infectados pelo T. cruzi com aumento no n?mero de parasitos circulantes.After more than 100 years of its discovery, until today, the Trypanosoma cruzi infection still demands an effective therapeutic strategy. The therapy with the Benznidazole shows effectiveness on T. cruzi control in the acute phase, however, it displays unsatisfactory results in chronic phase exhibiting high toxicity which leads to the therapy abandonment. New pharmacological approaches have been proposed aiming parasite eradication and, in parallel, the regulation of the inflammatory response since it is a key element of the cardiac pathogenesis related to this protozoan. Here, we highlight the anti-helmintic Nitazoxanide (NTZ) in a different dose (100, 200, 400, 600, 800, 1000 and 1200 mg / kg) administered by gavage for 10 days (12 to12 hours) in C57BL/ 6 mice (n = 9) infected with 4,000 trypomastigote forms of T. cruzi (Y strain). The parasitemia was performed daily and after euthanasia (11th day post infection), the plasma and heart homogenate were used for the liver enzymes TGO and TGP assays and for ELISA (TNF, IL-10, IL-17 and CCL2). An increase circulating parasites were observed in all infected NTZ-treated animals, but no changes were observed with the relative heart mass. However, 40% mortality was observed in the animals receiving 1200 mg/kg dose of this drug. The production of inflammatory mediators (TNF, CCL2 and IL-10) reduced in the NTZ-treated-groups, when compared to the uninfected/untreated animals. Regarding the production of IL-17, its reduction was observed with the NTZ-treated animals in comparison to the infected control. No change was observed with the TGP associated with the infection and treatments, but higher TGO levels were detected at the doses of 800, 1000 and 1200 mg/kg of NTZ. We conclude that the lower doses of NTZ showed partial regulation of the inflammatory mediators (TNF, IL-10, IL-17 and CCL2) in the acute phase of T. cruzi-infected C57BL/6 mice with an increase in the number of circulating parasites

The β-blocker carvedilol and the benznidazole modulate the cardiac immune response in the acute infection induced by Colombian strain of the Trypanosoma cruzi

BACKGROUND The infection led by Trypanosoma cruzi persists in mammalian tissues causing an inflammatory imbalance. Carvedilol (Cv), a non-selective beta blocker drug indicated to treat heart failure and antihypertensive has shown to promote antioxidant and immunomodulatory properties which might improve the inflammation induced by T. cruzi. OBJECTIVES Evaluate the role of Cv on the inflammatory response of C57BL/6 mice acutely infected with the Colombian strain of T. cruzi. METHODS Animals were infected with the Colombian strain of T. cruzi and treated with Cv (25 mg/kg/day), benznidazole (Bz) (100 mg/kg/day) or their combination. On the 28th day of infection and 23 days of treatment, the euthanasia occurred, and the heart preserved for histopathological, oxidative stress (SOD, catalase, TBARs, carbonylated proteins) and plasma (CCL2, CCL5, TNF, IL-10) analyses. Parasitaemia and survival were assessed along the infection. FINDINGS Cv decreased TBARs, but increased the mortality rate, the parasitaemia and the levels of CCL2, CCL5, catalase and the inflammatory infiltrate in the cardiac tissue. Bz led the reduction of the inflammatory infiltrate and circulating levels of oxidative stress and inflammatory mediators in the infected mice. MAIN CONCLUSIONS Our data suggest that Cv, in this experimental model using the Colombian strain of T. cruzi, caused damage to the host