Depolarization of the tegument precedes morphological alterations in Echinococcus granulosus protoscoleces incubated with ivermectin

The nematocidal activity of ivermectin (IVM) largely arises from its activi ty as a potent agonist of muscular and neuronal glutamate-gated chloride ch annels. A cestocidal effect has also been suggested following in vitro trea tments, but the molecular basis of this activity is not clear. We studied t he effect of IVM on the metacestode stage of the tapeworm Echinococcus gran ulosus by assessing the viability, ultrastructure, and tegumental membrane potential as a function of drug concentration and incubation time. Concentr ations of 0.1 and 1.0 mug/ml of IVM had no effect on any of these three par ameters for up to 6 days of treatment. A concentration of 10 mug/ml, howeve r, elicited a sequence of alterations that started with a similar to 20-mV depolarization of the tegumental membrane, and was followed by rostellar di sorganization, rigid paralysis and, eventually, loss of viability. It is li kely that the IVM-induced depolarization of the tegument acts as the signal that initiates the cascade of degenerative processes that leads to the par asite's death. This would place the tegument as the primary target of actio n of IVM on cestodes. As an appropriate chemotherapy for the hydatid diseas e is still lacking, the cestocidal effect of IVM reported here is worth con sidering.