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

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...

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Bibliographic Details
Published in:Immunobiology (1979) 2010-12, Vol.215 (12), p.980-986
Main Authors: Domingues Santos, Carla, Loria, Roger M, Rodrigues Oliveira, Luiz Gustavo, Collins Kuehn, Christian, Alonso Toldo, Míriam Paula, Albuquerque, Sérgio, do Prado Júnior, José Clóvis
Format: Article
Language:English
Subjects:
Acute Disease
Advanced Basic Science
Allergy and Immunology
Animals
Benznidazole
Chagas Disease - blood
Chagas Disease - drug therapy
Chagas Disease - mortality
Cytokines
Dehydroepiandrosterone Sulfate - pharmacology
Dehydroepiandrosterone Sulfate - therapeutic use
Dehydroepiandrosterone-sulfate
Drug Therapy, Combination
Interferon-gamma - metabolism
Interleukin-2 - metabolism
Macrophages, Peritoneal - drug effects
Macrophages, Peritoneal - metabolism
Male
Nitrite Trypanosoma cruzi
Nitrites - metabolism
Nitroimidazoles - pharmacology
Nitroimidazoles - therapeutic use
Parasitemia - blood
Parasitemia - prevention & control
Rats
Rats, Wistar
Species Specificity
Survival Rate
Time Factors
Treatment Outcome
Trypanocidal Agents - pharmacology
Trypanocidal Agents - therapeutic use
Trypanosoma cruzi
Trypanosoma cruzi - classification
Trypanosoma cruzi - drug effects
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Summary: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.
ISSN:0171-2985
1878-3279
DOI:10.1016/j.imbio.2009.11.002