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Could angiotensin-modulating drugs be relevant for the treatment of Trypanosoma cruzi infection? A systematic review of preclinical and clinical evidence

Published online by Cambridge University Press:  20 February 2019

Thaiany G. Souza-Silva
Affiliation:
Department of Structural Biology, Institute of Biomedical Sciences, Federal University of Alfenas, Alfenas, 37130-001, Minas Gerais, Brazil
Lívia F. Diniz
Affiliation:
Department of Pathology and Parasitology, Institute of Biomedical Sciences, Federal University of Alfenas, Alfenas, 37130-001, Minas Gerais, Brazil
Ana Lia Mazzeti
Affiliation:
Department of Pathology and Parasitology, Institute of Biomedical Sciences, Federal University of Alfenas, Alfenas, 37130-001, Minas Gerais, Brazil
Andrea A. S. Mendonça
Affiliation:
Department of Structural Biology, Institute of Biomedical Sciences, Federal University of Alfenas, Alfenas, 37130-001, Minas Gerais, Brazil
Reggiani V. Gonçalves
Affiliation:
Department of Animal Biology, Federal University of Viçosa, Viçosa, 36570-000, Minas Gerais, Brazil
Rômulo D. Novaes*
Affiliation:
Department of Structural Biology, Institute of Biomedical Sciences, Federal University of Alfenas, Alfenas, 37130-001, Minas Gerais, Brazil
*
Author for correspondence: Rômulo D. Novaes, E-mail: romuonovaes@yahoo.com.br; romulo.novaes@unifal-mg.edu.br

Abstract

Although leucocytes are targets of renin-angiotensin system (RAS) effector molecules and RAS-modulating drugs exert immunomodulatory effects, their impact on Trypanosoma cruzi infection remains poorly understood. By using the framework of a systematic review, we integrated the preclinical and clinical evidence to investigate the relevance of angiotensin-inhibiting drugs on T. cruzi infections. From a comprehensive and structured search in biomedical databases, only original studies were analysed. In preclinical and clinical studies, captopril, enalapril and losartan were RAS-modulating drugs used. The main in vitro findings indicated that these drugs increased parasite uptake per host cells, IL-12 expression by infected dendritic cells and IFN-γ by T lymphocytes, in addition to attenuating IL-10 and IL-17 production by CD8 + T cells. In animal models, reduced parasitaemia, tissue parasitism, leucocytes infiltration and mortality were often observed in T. cruzi-infected animals receiving RAS-modulating drugs. In patients with Chagas’ disease, these drugs exerted a controversial impact on cytokine and hormone levels, and a limited effect on cardiovascular function. Considering a detailed evaluation of reporting and methodological quality, the current preclinical and clinical evidence is at high risk of bias, and we hope that our critical analysis will be useful in mitigating the risk of bias in further studies.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2019 

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