Combined treatment of heterocyclic analogues and benznidazole upon Trypanosoma cruzi in vivo

Denise da Gama Jaén Batista, Marcos Meuser Batista, Gabriel Melo de Oliveira, Constança Carvalho Britto, Ana Carolina Mondaine Rodrigues, Chad E. Stephens, David W. Boykin, Maria de Nazaré Correia Soeiro

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Chagas disease caused by Trypanosoma cruzi is an important cause of mortality and morbidity in Latin America but no vaccines or safe chemotherapeutic agents are available. Combined therapy is envisioned as an ideal approach since it may enhance efficacy by acting upon different cellular targets, may reduce toxicity and minimize the risk of drug resistance. Therefore, we investigated the activity of benznidazole (Bz) in combination with the diamidine prodrug DB289 and in combination with the arylimidamide DB766 upon T. cruzi infection in vivo. The oral treatment of T.cruzi-infected mice with DB289 and Benznidazole (Bz) alone reduced the number of circulating parasites compared with untreated mice by about 70% and 90%, respectively. However, the combination of these two compounds decreased the parasitemia by 99% and protected against animal mortality by 100%, but without providing a parasitological cure. When Bz (p.o) was combined with DB766 (via ip route), at least a 99.5% decrease in parasitemia levels was observed. DB766+Bz also provided 100% protection against mice mortality while Bz alone provided about 87% protection. This combined therapy also reduced the tissular lesions induced by T. cruzi infection: Bz alone reduced GPT and CK plasma levels by about 12% and 78% compared to untreated mice group, the combination of Bz with DB766 resulted in a reduction of GPT and CK plasma levels of 56% and 91%. Cure assessment through hemocultive and PCR approaches showed that Bz did not provide a parasitological cure, however, DB766 alone or associated with Bz cured ≥13% of surviving animals.

Original languageEnglish (US)
Article numbere22155
JournalPloS one
Volume6
Issue number7
DOIs
StatePublished - Aug 1 2011

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Trypanosoma cruzi
parasitemia
mice
therapeutics
Chagas disease
Latin America
drug resistance
Parasitemia
lesions (animal)
infection
morbidity
mouth
animals
Mortality
Animals
vaccines
toxicity
parasites
Pentamidine
Plasmas

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

da Gama Jaén Batista, D., Batista, M. M., de Oliveira, G. M., Britto, C. C., Rodrigues, A. C. M., Stephens, C. E., ... de Nazaré Correia Soeiro, M. (2011). Combined treatment of heterocyclic analogues and benznidazole upon Trypanosoma cruzi in vivo. PloS one, 6(7), [e22155]. https://doi.org/10.1371/journal.pone.0022155

Combined treatment of heterocyclic analogues and benznidazole upon Trypanosoma cruzi in vivo. / da Gama Jaén Batista, Denise; Batista, Marcos Meuser; de Oliveira, Gabriel Melo; Britto, Constança Carvalho; Rodrigues, Ana Carolina Mondaine; Stephens, Chad E.; Boykin, David W.; de Nazaré Correia Soeiro, Maria.

In: PloS one, Vol. 6, No. 7, e22155, 01.08.2011.

Research output: Contribution to journalArticle

da Gama Jaén Batista, D, Batista, MM, de Oliveira, GM, Britto, CC, Rodrigues, ACM, Stephens, CE, Boykin, DW & de Nazaré Correia Soeiro, M 2011, 'Combined treatment of heterocyclic analogues and benznidazole upon Trypanosoma cruzi in vivo', PloS one, vol. 6, no. 7, e22155. https://doi.org/10.1371/journal.pone.0022155
da Gama Jaén Batista D, Batista MM, de Oliveira GM, Britto CC, Rodrigues ACM, Stephens CE et al. Combined treatment of heterocyclic analogues and benznidazole upon Trypanosoma cruzi in vivo. PloS one. 2011 Aug 1;6(7). e22155. https://doi.org/10.1371/journal.pone.0022155
da Gama Jaén Batista, Denise ; Batista, Marcos Meuser ; de Oliveira, Gabriel Melo ; Britto, Constança Carvalho ; Rodrigues, Ana Carolina Mondaine ; Stephens, Chad E. ; Boykin, David W. ; de Nazaré Correia Soeiro, Maria. / Combined treatment of heterocyclic analogues and benznidazole upon Trypanosoma cruzi in vivo. In: PloS one. 2011 ; Vol. 6, No. 7.
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