Effects of dehydroepiandrosterone-sulfate (DHEA-S) and benznidazole treatments during acute infection of two different Trypanosoma cruzi strains.
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.
Santos
Carla Domingues
CD
Laboratório de Parasitologia, Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto FCFRP-USP, Universidade de São Paulo, Avenida do Café s/no, 14040-903 Ribeirão Preto, SP, Brasil. carladom@fcfrp.usp.br
Loria
Roger M
RM
Oliveira
Luiz Gustavo Rodrigues
LG
Kuehn
Christian Collins
CC
Toldo
Míriam Paula Alonso
MP
Albuquerque
Sérgio
S
do Prado
José Clóvis
JC
D000208:Acute Disease; D000818:Animals; D014355:Chagas Disease / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D019314:Dehydroepiandrosterone Sulfate / Q000494:pharmacology* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009573:Nitrites / Q000378:metabolism; D009593:Nitroimidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D018512:Parasitemia / Q000097:blood / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D014344:Trypanocidal Agents / Q000494:pharmacology / Q000627:therapeutic use; D014349:Trypanosoma cruzi / Q000145:classification / Q000187:drug effects*
D007376:Interleukin-2; D009573:Nitrites; D009593:Nitroimidazoles; D014344:Trypanocidal Agents; D019314:Dehydroepiandrosterone Sulfate; D007371:Interferon-gamma; C009999:benzonidazole