Effects of dehydroepiandrosterone-sulfate (DHEA-S) and benznidazole treatments during acute infection of two different Trypanosoma cruzi strains

Author(s)

Santos, Carla Domingues ^[1] ; Loria, Roger M. ^[2] ; Rodrigues Oliveira, Luiz Gustavo ^[1] ; Kuehn, Christian Collins ^[1] ; Alonso Toldo, Miriam Paula ^[1] ; Albuquerque, Sergio ^[1] ; do Prado Junior, Jose Clovis ^[1]

Affiliation

^[1] Univ Sao Paulo, Parasitol Lab, Dept Anal Clin Toxicol & Bromatol, Fac Ciencias Farmaceut Ribeirao Preto, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Virginia Commonwealth Univ, Dept Microbiol & Immunol Pathol & Emergency Med, Richmond, VA 23298 - USA

• Document type: Journal article
• Source: Immunobiology; v. 215, n. 12, p. 980-986, DEC 2010.
• Web of Science Citations: 7

Abstract

A significant role for hormones in regulating the balance of Th1- and Th2-associated cytokines with a role in modulating diseases has been accumulating. Previously, we reported that dehydroepiandrosterone (DHEA), the most abundant steroid hormone synthesized by the adrenal cortex, markedly reduced the blood and tissue parasites in experimentally Trypanosoma cruzi-infected rats. Based on these findings, the main purpose of this study was to investigate the effect of dehydroepiandrosterone-sulfate ester (DHEA-S) therapy alone or in combination with benznidazole (BNZ) (recommended in Brazil for the treatment of T. cruzi infection) will be effective during the acute phase of two different lineages of T. cruzi strains: type I (Y strain) and type II (Bolivia strain) of T. cruzi. Administration of either DHEA-S or BNZ alone or in combination significantly reduced the Y strain parasite load as compared with untreated. Furthermore treatment with DHEA-S resulted in Bolivia strain clearance. This protective effect of DHEA-S was associated with the host's immune response, as evidence by enhanced levels of interferon-gamma and interleukin-2. DHEA-S treatment also increased peritoneal macrophages levels and nitrite production. DHEA-S treatment was effective in reducing the mortality rate as compared to BNZ alone or to combiner DHEA-S+BNZ treatment of T. cruzi Bolivia strain infected animals. These findings suggest that hormonal therapy may have a protective effect in the treatment of T. cruzi infection. (C) 2009 Elsevier GmbH. All rights reserved. (AU)

• FAPESP's process: 07/08388-7 - Dehydroepiandrosterone: the treatment effects with its metabolites (DHEA-sulfate, androstenediol e androstenetriol) and benzonidazol associations during the acute phase of experimental infection by different strains of Trypanosoma cruzi
• Grantee: Carla Domingues dos Santos Sponchiado
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 08/04763-0 - Dehydroepiandrosterone: the treatment effects with its metabolites (DHEA-sulfate, androstenediol e androstenetriol) and benzonidazol association during the acute phase of experimental infection by different strains of Trypanosoma cruzi
• Grantee: José Clóvis do Prado Júnior
• Support Opportunities: Regular Research Grants