Combination therapy with benznidazole and doxycycline shows no additive effect to monotherapy with benznidazole in mice infected with the VL-10 strain of the Trypanosoma cruzi.

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dc.contributor.authorCarneiro, Ana Cláudia Alvarenga
dc.contributor.authorCosta, Guilherme de Paula
dc.contributor.authorFerreira, Cyntia Silva
dc.contributor.authorRamos, Isalira Peroba Rezende
dc.contributor.authorSarandy, Mariáurea Matias
dc.contributor.authorLeite, Ana Luísa Junqueira
dc.contributor.authorMenezes, Ana Paula de Jesus
dc.contributor.authorSilva, Breno de Mello
dc.contributor.authorNogueira, Katiane de Oliveira Pinto Coelho
dc.date.accessioned2020-03-13T11:43:16Z
dc.date.available2020-03-13T11:43:16Z
dc.date.issued2020
dc.description.abstractBackground: Chagas heart disease is the most important clinical manifestation of Trypanosoma cruzi infection. Pharmacological therapies have been proposed aiming to reduce inflammatory response and cardiac damage in infected hosts. In this study, we investigated the use of doxycycline (Dox), in a sub-antimicrobial dose, in monotherapy and in combination with benznidazole (Bz) during the acute phase of infection with the VL-10 strain of T. cruzi, evaluating the therapeutic effect during the acute and chronic phases of the infection. Methods and results: C57BL/6 mice were treated for 20 days with Dox (30 mg/kg), Bz (100 mg/kg), or both drugs in combination starting 9 days after infection. Parasitemia was measured during the acute phase and the animals were monitored for 12 months, after which echocardiography analysis was performed. Blood samples were obtained from euthanized mice for CCL2, CCL5, IL-10 analysis, and cardiac fragments were collected for histopathological evaluation. Dox treatment did not ameliorate parasitological/inflammatory parameters but reduced the cardiac collagen neoformation (CN) in 35%. In contrast, Bz administration reduced parasitemia, plasma levels of CCL2 and CCL5, and cardiac infiltration during acute infection, and reduced the level of IL-10 and CN (95%) at 12 months. Dox was unable to improve ejection fraction, while Bz treatment ameliorated the ejection fraction. No additive effect was observed in combination therapy. Conclusion: Dox monotherapy is not effective in the acute or chronic phases of experimental cardiomyopathy induced by the VL-10 strain of T. cruzi. Furthermore, combination therapy with Dox does not potentiate the effects of Bz monotherapy.pt_BR
dc.identifier.citationCARNEIRO, A. C. A. et al. Combination therapy with benznidazole and doxycycline shows no additive effect to monotherapy with benznidazole in mice infected with the VL-10 strain of the Trypanosoma cruzi. International Journal of Cardiology, v. 299, p. 243-248, jan. 2020. Disponível em: <https://www.sciencedirect.com/science/article/pii/S0167527319307442?via%3Dihub>. Acesso em: 10 fev. 2020.pt_BR
dc.identifier.doihttps://doi.org/10.1016/j.ijcard.2019.07.047pt_BR
dc.identifier.issn0167-5273
dc.identifier.urihttp://www.repositorio.ufop.br/handle/123456789/11995
dc.identifier.uri2https://www.sciencedirect.com/science/article/pii/S0167527319307442?via%3Dihubpt_BR
dc.language.isoen_USpt_BR
dc.rightsrestritopt_BR
dc.subjectInflammationpt_BR
dc.subjectDoxycyclinept_BR
dc.subjectEchocardiographypt_BR
dc.titleCombination therapy with benznidazole and doxycycline shows no additive effect to monotherapy with benznidazole in mice infected with the VL-10 strain of the Trypanosoma cruzi.pt_BR
dc.typeArtigo publicado em periodicopt_BR
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