Anthelminthic activity of glibenclamide on secondary cystic echinococcosis in mice

LOOS, JULIA A.; CHURIO, MARÍA SANDRA; CUMINO, ANDREA C.

PLOS NEGLECTED TROPICAL DISEASES

PUBLIC LIBRARY SCIENCE

Año: 2017 vol. 11

1935-2735

Cystic echinococcosis (CE) is a worldwide parasitic zoonosis caused by the larval stage ofEchinococcus granulosus. Current chemotherapy against this disease is based on theadministration of benzimidazoles (BZMs). However, BZM treatment has a low cure rate andcauses several side effects. Therefore, new treatment options are needed. The antidiabeticdrug glibenclamide (Glb) is a second-generation sulfonylurea receptor inhibitor that has beenshown to be active against protozoan parasites. Hence, we assessed the in vitro and in vivopharmacological effects of Glb against the larval stage of E. granulosus. The in vitro activitywas concentration dependent on both protoscoleces and metacestodes. Moreover, Glb combinedwith the minimum effective concentration of albendazole sulfoxide (ABZSO) was demonstratedto have a greater effect on metacestodes in comparison with each drug alone.Likewise, there was a reduction in the cyst weight after oral administration of Glb to infectedmice (5 mg/kg of body weight administered daily for a period of 8 weeks). However, in contrastto in vitro assays, no differences in effectiveness were found between Glb + albendazole(ABZ) combined treatment and Glb monotherapy. Our results also revealed mitochondrialmembrane depolarization and an increase in intracellular Ca2+ levels in Glb-treated protoscoleces.In addition, the intracystic drug accumulation and our bioinformatic analysis using theavailable E. granulosus genome suggest the presence of genes encoding sulfonylurea transportersin the parasite. Our data clearly demonstrated an anti-echinococcal effect of Glb onE. granulosus larval stage. Further studies are needed in order to thoroughly investigate themechanism involved in the therapeutic response of the parasite to this sulfonylurea.