Affordable Access

deepdyve-link
Publisher Website

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.

Authors
  • Carneiro, Ana Cláudia Alvarenga1
  • Costa, G P1
  • Ferreira, Cyntia Silva2
  • Ramos, Isalira Peroba Rezende3
  • Sarandy, Mariáurea Matias4
  • Leite, Ana Luísa Junqueira1
  • Menezes, A P J1
  • Silva, B M2
  • Nogueira, K O P C5
  • Carvalho, A C C3
  • Gonçalves, Reggiani Vilela4
  • Talvani, André6
  • 1 Laboratório de Imunobiologia da Inflamação, Departamento Ciências Biológicas, Universidade Federal de Ouro Preto, Minas Gerais, Brazil. , (Brazil)
  • 2 Laboratório de Biologia e Tecnologia de Micro-organismos, Departamento Ciências Biológicas, Universidade Federal de Ouro Preto, Minas Gerais, Brazil. , (Brazil)
  • 3 Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil. , (Brazil)
  • 4 Laboratório de Patologia Experimental, Departamento de Biologia Animal, Universidade Federal de Viçosa Minas Gerais, Brazil. , (Brazil)
  • 5 Laboratório de Biomateriais e Patologia Experimental, Departamento Ciências Biológicas, Universidade Federal de Ouro Preto, Minas Gerais, Brazil. , (Brazil)
  • 6 Laboratório de Imunobiologia da Inflamação, Departamento Ciências Biológicas, Universidade Federal de Ouro Preto, Minas Gerais, Brazil. Electronic address: [email protected] , (Brazil)
Type
Published Article
Journal
International journal of cardiology
Publication Date
Jan 15, 2020
Volume
299
Pages
243–248
Identifiers
DOI: 10.1016/j.ijcard.2019.07.047
PMID: 31353153
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. 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. 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. Copyright © 2019 Elsevier B.V. All rights reserved.

Report this publication

Statistics

Seen <100 times