Interfer?ncia da terapia com o betabloqueador Carvedilol na resposta inflamat?ria card?aca aguda em camundongos C57BL/6 infectados pela cepa colombiana 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.A resposta inflamat?ria gerada pela infec??o pelo Trypanosoma cruzi promove altera??es morfofisiol?gicas nas c?lulas card?acas de hospedeiros mam?feros. Esta inflama??o progressiva contribui para a gera??o de um quadro patol?gico de car?ter fibrog?nico culminando em poss?veis altera??es estruturais/ funcionais ao cora??o. F?rmacos com propriedades cardiovasculares e prescritos no manejo cl?nico de indiv?duos chag?sicos t?m sido investigados por suas a??es imunomodulat?rias. Nesta proposta, foram avaliadas as a??es do betabloqueador Carvedilol (CV) e do benznidazol (BZ), em camundongos machos da linhagem C57BL/6, infectados com 50 formas tripomastigotas da cepa Colombiana do Trypanosoma cruzi, e agrupados de acordo com as seguintes interven??es: (I) 15 animais infectados que n?o receberam tratamento (II) 15 animais tratados com 100mg/Kg/dia de BZ (III) 15 animais tratados com o CV 25mg/kg/dia (IV) 15 animais tratados com a combina??o dos f?rmacos BZ 100mg/kg/dia e CV 25mg/kg/dia. Al?m disso, foram utilizados 10 animais como controle n?o infectado. A a??o do betabloqueador (CV) 25 mg/kg e/ ou BZ 100 mg/kg, foi avaliada ap?s 28 dias de infec??o, e 23 dias de tratamento, per?odo an?logo ? fase aguda. A eutan?sia ocorreu no 280 dia, sendo o cora??o conservado para an?lise histopatol?gica, e avalia??o de Estresse oxidativo (SOD, catalase, TBARs, prote?nas carboniladas), e o sangue/plasma destinado aos ensaios imunoenzim?ticos (CCL2, CCL5, TNF-alfa, IL-10), al?m de avaliar a parasitemia e sobrevida ao longo da infec??o. Desta maneira, observou-se, que a terapia com o CV elevou a mortalidade dos animais, a parasitemia, assim como o n?vel das quimiocinas CCL2 e CCL5 no tecido muscular card?aco, mas por outro lado reduziu os n?veis de TNF. Em contrapartida, o CV n?o alterou o perfil da citocina regulat?ria IL-10. O tratamento em monoterapia com o CV promoveu, ainda, o aumento do infiltrado inflamat?rio no tecido muscular card?aco mediante infec??o pelo T. cruzi, em rela??o aos animais infectados n?o tratados. Conclui-se que o CV n?o foi capaz de oferecer prote??o card?aca ao hospedeiro mam?fero durante a fase aguda da infec??o pelo T. cruzi por elevar os mediadores inflamat?rios e, consequentemente, o infiltrado inflamat?rio card?aco. Outros estudos em diferentes modelos experimentais tornam-se necess?rios para compreender as a??es pleiotr?pica do CV em roedores, uma vez que em seres humanos este f?rmaco apresenta propriedade protetora card?aca em indiv?duos cardiopatas cr?nicos.The inflammatory response generated by Trypanosoma cruzi infection promotes morphophysiological changes in the cardiac cells of mammalian hosts. This progressive inflammation contributes to the generation of a pathological picture of fibrogenic character culminating in possible structural / functional changes to the heart. Drugs with cardiovascular properties and prescribed in the clinical management of chagasic individuals have been investigated for their immunomodulatory actions. In this proposal, the actions of the beta blocker Carvedilol (CV) and benznidazole (BZ) were evaluated in infected male C57BL / 6 mice with 50 trypomastigote forms of the Trypanosoma cruzi Colombian strain, and grouped according to the following interventions: (I) 15 infected animals not receiving treatment (II) 15 animals treated with 100 mg / kg / day BZ (III) 15 treated animals With CV 25mg / kg / day (IV) 15 animals treated with the combination of drugs BZ 100mg / kg / day and CV 25mg / kg / day. In addition, 10 animals were used as uninfected control. The action of beta-blocker (CV) 25 mg / kg and / or Benznidazole (BZ) 100 mg/ kg, was evaluated after 28 days of infection, and 23 days of treatment, a period analogous to the acute phase. Euthanasia occurred at 28th day, and the heart was preserved for histopathological analysis and oxidative Estresse evaluation (SOD, catalase, TBARs, carbonylated proteins), and blood / plasma for immunoenzymatic assays (CCL2, CCL5, TNF-alpha, IL -10), in addition to evaluating parasitemia and survival throughout the infection. In this way, we observed that CV therapy increased the mortality of the animals, parasitemia, as well as the level of chemokines CCL2 and CCL5 in cardiac muscle tissue, but on the other hand it reduced TNF levels. In contrast, CV did not alter the IL-10 regulatory cytokine profile. The monotherapy treatment with CV also promoted the increase of inflammatory infiltrate in cardiac muscle tissue. T. cruzi infection in relation to untreated infected animals. It is concluded that CV was unable to provide cardiac protection to the mammalian host during the acute phase of T. cruzi infection by elevating inflammatory mediators and, consequently, cardiac inflammatory infiltrate. Other studies in different experimental models become necessary to understand the pleiotropic actions of CV in rodents, since in humans this drug presents cardiac protective property in chronic cardiopathy individuals