RESUMO
Trypanosomatids possess an unremitting requirement for distinctive endogenous sterols for their life cycle and cannot use the copious availability of cholesterol existing in their mammalian hosts. Exhaustion of endogenous sterols such as ergosterol or of its next biosynthetic product 24-ethylcholesta-5,7,22-trien- 3ß-ol brings forth an inhibition of proliferation on Trypanosoma cruzi, the etiologic agent of American trypanosomiasis or Chagas disease. These metabolites are crucial; consequently, the enzymes implicated in catalyzing their formation constitute interesting molecular targets for drug design. Selective inhibition of an enzyme associated to the ergosterol biosynthesis will produce T. cruzi cell arrest. Trypanosomatids, fungi, and yeasts have need of these endogenous sterols for cell viability and growth. In fact, some effective ergosterol biosynthesis inhibitors bearing suitable pharmacokinetic properties in mammals have become putative antiparasitic agents by inducing almost complete parasitological cure in both acute and chronic experimental Chagas disease. WC-9 (compound 7; 4-phenoxyphenoxyethyl thiocyanate) holds our attention bearing in mind that this compound exhibits ED50values at the low nanomolar range against the clinically more relevant replicative form of T. cruzi (amastigotes). The cellular activity of WC-9 is due to an exhaustion of endogenous sterols demonstrating a blockade of the biosynthetic pathway at a pre-squalene level.
Assuntos
Antiparasitários/farmacologia , Doença de Chagas/tratamento farmacológico , Desenho de Fármacos , Éteres Fenílicos/farmacologia , Tiocianatos/farmacologia , Toxoplasmose/tratamento farmacológico , Animais , Antiparasitários/química , Antiparasitários/uso terapêutico , Humanos , Éteres Fenílicos/química , Éteres Fenílicos/uso terapêutico , Tiocianatos/química , Tiocianatos/uso terapêutico , Toxoplasma/efeitos dos fármacos , Tripanossomicidas/química , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacosRESUMO
Diabetes has reached epidemic levels in the whole world, and the use of bioactive compounds that may have the capacity to prevent and treat diabetes is of great interest. Sulforaphane (SFN) is a compound which is found in cruciferous vegetables and that acts as both a potent antioxidant and regulator of gene expression. The aim of this study was to evaluate the effect of SFN in diabetes induced by streptozotocin (STZ). Male Wistar rats were gavaged with water or 0.1, 0.25, or 0.5 mg/kg of SFN before an injection of STZ (80 mg/kg). Animals treated with SFN showed fasting glycemia, insulin sensitivity, and hepatic glycogen concentrations, similar to the control group (nondiabetic), and different from the diabetic group. Diabetic animals also presented elevated levels of serum triacylglycerols (TAG), urea, and creatinine, and all SFN doses were able to reverse these alterations. However, the same doses of SFN accentuated alterations in total cholesterol, alanine, and aspartate aminotransferase levels, and had no effect on hepatic TAG, HDL cholesterol, and uptake of 2-deoxy glucose in adipose tissue and soleum muscle. Based on the effects inferred by the present data, SFN presented some positive effects against diabetes induction, although the impairment of hepatic function and cholesterol levels were aggravated after treatment with the compound.
Assuntos
Antioxidantes/uso terapêutico , Diabetes Mellitus Tipo 1/prevenção & controle , Suplementos Nutricionais , Glucose/metabolismo , Hipoglicemiantes/uso terapêutico , Resistência à Insulina , Tiocianatos/uso terapêutico , Animais , Antioxidantes/administração & dosagem , Antioxidantes/efeitos adversos , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/fisiopatologia , Nefropatias Diabéticas/prevenção & controle , Suplementos Nutricionais/efeitos adversos , Insuficiência Hepática/complicações , Insuficiência Hepática/etiologia , Hipercolesterolemia/complicações , Hipercolesterolemia/etiologia , Hiperglicemia/prevenção & controle , Hipertrigliceridemia/complicações , Hipertrigliceridemia/prevenção & controle , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Gordura Intra-Abdominal/metabolismo , Isotiocianatos , Fígado/metabolismo , Fígado/fisiopatologia , Glicogênio Hepático/metabolismo , Masculino , Músculo Esquelético/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Estreptozocina , Sulfóxidos , Tiocianatos/administração & dosagem , Tiocianatos/efeitos adversosRESUMO
With the aim to evaluate the efficacy of four vermicides, praziquantel, mebendazole, nitroscanate and triclorfon in the control of Bothriocephalus acheilognathi in carps, one hundred and sixty, two year-old carps (Ctenopharyngodon idellus) with an average weight of 120 g and a mean parasitic burden of 115.5 parasites/fish were used. Five groups of 30 fish each were randomly formed. Each group was then subdivided in three groups, each of 10 individuals/pond. The three subgroups of group A received 30, 50 and 70 mg/Kg of praziquantel, respectively. Groups B and C received 2.2, 4.4, and 6.8 mg/Kg of mebendazole suspension and mebendazole solution respectively; groups D and E received 10, 30, 50 mg/Kg; and 2.0, 4.0, 6.0 mg/Kg of nitroscanate and trichlorfon respectively. Group F of 10 fish remained as non-treated control. Praziquantel showed 100% of efficacy for all doses, therefore it was excluded from the statistical analysis. The subgroups B, C, D and E compared with the non-treated control were statistically significant (P < 0.01); showing in all treatments an additive effect, the higher the dose the better efficacy, except trichlorfon which showed a different tendency, having no explanation on that matter.