FLUBENDAZOLE INDUCE PROTOSCOLICIDAL EFFECT BY A CALCIUM-DEPENDENT MECHANISM ON ECHINOCOCCUS SP.

CUMINO, ANDREA; **ELISSONDO, MARÍA.; *SALERNO, GRACIELA, AND ** DENEGRI, GUILLERMO.

Rosario, Argentina (12-15 Noviembre)

Congreso; XLII Annual Meeting SAIB; 2006

Argentine Society for Biochemestry and Molecular Biology Research

The chemotherapeutic treatment of human echinococcosis remains unsolved. Benzimidazole (BZD) as mebendazole (MBZ) and albendazole (ABZ) are broad-spectrum antihelminthic agents and 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 although little is known about the molecular bases of their multiple biological activities. Recently has been demonstrated a clear in vitro effect of flubendazole (FLBZ), against E. granulosus larvae (Elissondo et al., 2006), whereas vitality tests were consistent with a faster appearance of morphological damage than larvae cultured with others BZD. Hence, we examined the biochemical and molecular changes in vitro of this halogen-derivate BZD on protoscoleces. We observed that only FLBZ caused a rapid increase in intracellular Ca2+ concentration determined by labeling with Fluo-3 AM and imaged by a confocal laser microscope after treatment with ruthenium red and EGTA for distinguishing subcellular signal localization. On the other hand, these results were correlated with significant glycogen depletion and mitochondrial gene expression. Therefore FLBZ, as others halogeno-benzimidazoles (Andrzejewska et al., 2004), may interfere with a wide spectrum of cell regulatory mechanisms.