RESUMO
The effect of 16α-bromoepiandrosterone (EpiBr), a dehydroepiandrosterone (DHEA) analogue, was tested on the cysticerci of Taenia solium, both in vitro and in vivo. In vitro treatment of T. solium cultures with EpiBr reduced scolex evagination, growth, motility, and viability in dose- and time-dependent fashions. Administration of EpiBr prior to infection with T. solium cysticerci in hamsters reduced the number and size of developed taenias in the intestine, compared with controls. These effects were associated to an increase in splenocyte proliferation in infected hamsters. These results leave open the possibility of assessing the potential of this hormonal analogue as a possible antiparasite drug, particularly in cysticercosis and taeniosis.
Assuntos
Androsterona/análogos & derivados , Antiparasitários/farmacologia , Cisticercose/tratamento farmacológico , Taenia solium/efeitos dos fármacos , Androsterona/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Cricetinae , Desidroepiandrosterona/análogos & derivados , Desidroepiandrosterona/química , Entamoeba histolytica/efeitos dos fármacos , Intestinos/parasitologia , Masculino , Mesocricetus , Músculos/parasitologia , Baço/citologia , Baço/parasitologia , SuínosRESUMO
The effect of the dehydroepiandrosterone analog 16alpha-bromoepiandrosterone (EpiBr) was tested on the tapeworm Taenia crassiceps and the protist Entamoeba histolytica, both in vivo and in vitro. Administration of EpiBr prior to infection with cysticerci in mice reduced the parasite load by 50% compared with controls. EpiBr treatment induced 20% reduction on the development of amoebic liver abscesses in hamsters. In vitro treatment of T. crassiceps and E. histolytica cultures with EpiBr, reduced reproduction, motility and viability in a dose- and time-dependent fashion. These results leave open the possibility of assessing the potential of this hormonal analog as a possible anti-parasite drug, including cysticercosis and amoebiasis.
Assuntos
Amebíase/parasitologia , Androsterona/análogos & derivados , Anti-Helmínticos/farmacologia , Antiprotozoários/farmacologia , Cisticercose/parasitologia , Entamoeba histolytica/efeitos dos fármacos , Taenia/efeitos dos fármacos , Amebíase/tratamento farmacológico , Androsterona/administração & dosagem , Androsterona/farmacologia , Animais , Anti-Helmínticos/administração & dosagem , Antiprotozoários/administração & dosagem , Sobrevivência Celular/efeitos dos fármacos , Cricetinae , Cisticercose/tratamento farmacológico , Feminino , Histocitoquímica , Abscesso Hepático/tratamento farmacológico , Abscesso Hepático/parasitologia , Abscesso Hepático/patologia , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Análise de SobrevidaRESUMO
BALB/c mice with pulmonary tuberculosis develop a T helper cell type 1 response that peaks at 3 weeks, temporarily controlling bacterial growth. Then bacterial proliferation recommences, accompanied by increasing interleukin (IL)-4 levels and decreasing interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and inducible nitric oxide synthase (iNOS) levels. These changes mimic those in the human disease. In a previous study, administration of dehydroepiandrosterone (DHEA) beginning on day 60 after infection reversed these changes and protected the mice. However, DHEA is suboptimal for human use, partly because it is readily metabolized into sex steroids. 16alpha-Bromoepiandrosterone (EpiBr; 16alpha -bromo-5alpha -androstan-3beta-ol-17-one) is a synthetic adrenal steroid derivative that does not enter sex steroid pathways. In the present study, when tuberculous BALB/c mice were treated with EpiBr 3 times/week beginning on day 60, inhibition of bacterial proliferation and increased expression of TNF-alpha, IFN-gamma, and iNOS were observed, although decreased expression of IL-4 was also observed. Moreover, when given as an adjunct to conventional chemotherapy, EpiBr enhanced bacterial clearance. Trials for the use of EpiBr in the treatment of human tuberculosis are now justified.