Flubendazole interferes with a wide spectrum of cell homeostatic mechanisms in Echinococcus granulosus protoscoleces

ANDREA C. CUMINO, MARÍA CELINA ELISSONDO, GUILLERMO M. DENEGRI

PARASITOLOGY INTERNATIONAL

Elsevier

Año: 2009 vol. 58 p. 270 - 277

1383-5769

The chemotherapeutic treatment of human echinococcosis is not completely solved. The broad-spectrum antihelminthic agents benzimidazole (BZD), mebendazole and albendazole are the only drugs licensed for treatment of hydatid cysts. These drugs bind directly to b-tubulin causing the disruption of microtubule-based processes in helminths. However, the molecular bases of their multiple biological activities are poorly understood. Recently, the effect of halogenated derivative flubendazole (FLBZ), against E. granulosus larvae has been conclusively demonstrated. The comparative effectiveness of FLBZ, among other BZDs, was shown by means of vitality tests and time for appearance of morphological damage of lavae. In the present study, we examined biochemical and molecular changes on protoscoleces treated with FLBZ. We show that FLBZ induces: 1) an increase in cytosolic free calcium, 2) a decrease of tubulin transcripts, 3) a reduction of mMDH expression and 4) a significant decrease of glycogen levels. These results are consistent with the existence of multiple targets for FLBZ, at least Ca2+ signaling and energy metabolism, and contribute to the understanding of the pharmaceutical properties of FLBZ for human echinococcosis treatment.