Anthelminthic activity of glibenclamide against experimental cystic echinococcosis

JULIA A. LOOS; VALERIA DÁVILA; ANDREA C. CUMINO

Chicago

Conferencia; 3rd World Conference on Parasitology and Pathogenesis; 2017

Statement of the Problem: Cystic echinococcosis is a worldwide parasitic zoonosis caused by the larval stage of Echinococcusgranulosus. Current chemotherapy against this disease is based on benzimidazoles (BZMs). However, BZM treatment results ina low cure rate and causes side effects. Therefore, new treatment options are needed. The antidiabetic drug glibenclamide (Glb) is asecond-generation sulfonylurea receptor inhibitor that has been shown to be active against protozoan parasites. The purpose of thisstudy is to investigate the in vitro and in vivo pharmacological effects of Glb against the larval stage of E. granulosus. Methodology& Theoretical Orientation: Viable protoscoleces and metacestodes were cultured in vitro with different concentrations of Glb and/orABZSO and mortality was calculated daily. Subsequently, E. granulosus-infected mice were orally treated with Glb and/or ABZ dailyfor 60 days. The hydatid cysts collected from the animals were weighed and analyzed by SEM. Findings: The in vitro Glb activity onboth protoscoleces and metacestodes was dependent on the concentration. In addition, the combination of Glb and ABZSO had agreater effect on metacestodes than each drug alone. Likewise, a reduction of the cyst weight was also found after administration ofGlb to infected mice. However, Glb + ABZ combined treatment not shown to be more effective than Glb monotherapy. Our resultsalso demonstrated mitochondrial membrane depolarization and increase of Ca+2 intracellular levels in Glb-treated protoscoleces.Moreover, the intracystic drug accumulation, the competition of Glb for 1-NPN binding site in protoscoleces, and the bioinformaticanalysis using the available E. granulosus genome, suggest the presence of genes encoding receptor and transporters of sulfonylureasin the parasite. Conclusion & Significance: Glb shows anthelmintic effect on E. granulosus larval stage. Further studies are needed tofully investigate the mechanism involved in the therapeutic response of the parasite to this sulfonylurea.