Avaliação do potencial de auronas na terapia da esquistossomose in vitro e em modelo murino

Abstract

Schistosomiasis is a disease caused by the helminth Schistosoma mansoni that affects about 240 million people in the world. Pharmacological therapy for this disease is still very restricted, and a search for new drugs is important. The aim of this work was to evaluate the pharmacological potential of three synthetic aurones in schistosomiasis models (in vitro and in vivo). In in vitro assays, worms were exposed to drugs (25 μM) as well as probes to investigate membrane permeability (FITC-Dextrans) and autophagosome formation (monodansylcadaverine). Compared at groups-controls, there was an increase in marking in all groups treated with the drugs, suggesting that all three aurones somehow intensify the formation of pore and autophagosomes in the adult worms. Additionally, the effect of inhibition of the aurones on potato apyrase, an isoform of NTPDase structurally related to the isoforms present in the parasites. In these assays, LS26 partially inhibited ATPase activity (at 15, 12 and 47%, in the 0.1mM, 0.001mM and 0.0001mM bands) and ADPasic activity (at 21.5%, at 0.001mM concentration), which indicates the relevance of further investigation of its potential as an inhibitor of NTPDases of S. mansoni. In the in vivo assays, LS26 and LS29 reduced the parasitic load in the treated animals (56.20% for those treated with LS26 50 mg/kg in two doses; and 57.61% for those treated with LS29 50 mg/kg, in tow doses, compared to the untreated control group). Furthermore, LS26 and LS29 caused an increase in the partial displacement of worms from the mesenteric veins to the hepatic vessels and they also interfered in the kinetics of egg development. In the evaluation of the level of lipid peroxidation in the liver, no significant difference was found between animals who were treated and untreated with LS26 and LS29. Finally, we reinforced that additional pharmacokinetic and pharmacodynamic studies should be done for a better understanding of the mechanisms of action of LS26 and LS29 for use in a formulation for the treatment of schistosomiasis