Avaliação do efeito tripanocida do eupomatenóide-5 por meio de abordagens de biologia celular e bioquímica : um possível mecanismo de ação






Chagas disease is considered a neglected disease that affects millions of people, but does not have an appropriate and effective treatment. The etiologic agent is the protozoan Trypanosoma cruzi that presents a complex life cycle alternating between a vertebrate host and an invertebrate. In the search for more effective and less toxic drugs, the research for active compounds to pharmaceutical formulations is necessary and a priority. Recently, the use of medicinal plants with this aim has grown around the world, including Brazil. Among the various plants used as medicines by the population, Piper regnellii var. pallescens (pariparoba) can be mentioned. There are several popular therapeutic effects of P. regnellii extracts found in the literature, as unblocker, diuretic, emollient, and wound healing. Recent studies have shown the antiproliferative activity of four neolignans extracts purified from leaves of P. regnellii var. pallescens against T. cruzi. Among the neolignans, eupomatenoid-5 caused important morphological and ultrastructural alterations and was more active and less toxic than Benznidazole, a drug used to treat Chagas disease. The aim of this study was to evaluate the effect of eupomatenoid-5 in trypomastigote forms and to investigate the possible mechanism of action on T. cruzi. The compound was active against trypomastigotes, where ultrastructural analysis showed effect on the membrane and vacuoles formation, confirming their potential trypanocidal. Epimastigotes treated with 23.8 μM of eupomatenoid-5 showed growth inhibition of 41.8% and when challenged with nontoxic concentrations (20 μM) and toxic (100 μM) H2O2 an inhibition of 50.6 and 92.4% was observed, respectively, with 120 h of incubation. Furthermore, treatment with eupomatenoid-5 caused lipoperoxidation in both trypomastigote and epimastigote forms compared to control. Cytometric analysis with rhodamine 123 showed that the eupomatenoid-5 led to depolarization of the mitochondrial membrane potencial of epimastigotes. The compound also increased the activity of the enzyme glucose-6-phosphate dehydrogenase (G6PD) followed by the consumption of H2O2 in epimastigote treated with 34.0, 85.0, and 170,0 μM for 24 h. Our results indicate that the trypanocidal action of eupomatenoid-5 may be associated with impairment of the antioxidant system of the parasite, leading to increased reactive oxygen species and consequently to parasite death.


medical microbiology tripanossoma cruzi chagas doença de protozoários patogênicos piperacea - uso terapêutico microbiologia médica chagas disease

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