TY - JOUR
T1 - Depolarization of the tegument precedes morphological alterations in Echinococcus granulosus protoscoleces incubated with ivermectin
AU - Pérez-Serrano, Jorge
AU - Grosman, Claudio
AU - Urrea-París, Maria
AU - Denegri, Guillermo
AU - Casado, Nieves
AU - Rodríguez-Caabeiro, Filomena
N1 - Funding Information:
Fig. 4 Time course of the tegumental membrane potential of protoscoleces incubated in Medium 199 containing: d no IVM; . 0.1 lg/ml IVM; m 1 lg/ml IVM; j 10 lg/ml IVM. Each data point represents the mean (TSD) of 60 membrane-potential measurements recorded on 60 different protoscoleces corresponding to three different batches of parasites Acknowledgements This paper is dedicated to the loving memory of the late Dr. Ignacio L. Reisin, who introduced us to the field of parasite electrophysiology. We are grateful to Merck, Sharp & Dohme (Munich, Germany) for supplying samples of ivermectin, and to Mr. A. Priego and Mr. J.A. Pérez (Electron Microscopy Service, Universidad de Alcalá) for their technical assistance. This work was supported by DGICYT project PM96–0014.
PY - 2001
Y1 - 2001
N2 - The nematocidal activity of ivermectin (IVM) largely arises from its activity as a potent agonist of muscular and neuronal glutamate-gated chloride channels. A cestocidal effect has also been suggested following in vitro treatments, but the molecular basis of this activity is not clear. We studied the effect of IVM on the metacestode stage of the tapeworm Echinococcus granulosus by assessing the viability, ultrastructure, and tegumental membrane potential as a function of drug concentration and incubation time. Concentrations of 0.1 and 1.0 μg/ml of IVM had no effect on any of these three parameters for up to 6 days of treatment. A concentration of 10 μg/ml, however, elicited a sequence of alterations that started with a ∼20-mV depolarization of the tegumental membrane, and was followed by rostellar disorganization, rigid paralysis and, eventually, loss of viability. It is likely that the IVM-induced depolarization of the tegument acts as the signal that initiates the cascade of degenerative processes that leads to the parasite's death. This would place the tegument as the primary target of action of IVM on cestodes. As an appropriate chemotherapy for the hydatid disease is still lacking, the cestocidal effect of IVM reported here is worth considering.
AB - The nematocidal activity of ivermectin (IVM) largely arises from its activity as a potent agonist of muscular and neuronal glutamate-gated chloride channels. A cestocidal effect has also been suggested following in vitro treatments, but the molecular basis of this activity is not clear. We studied the effect of IVM on the metacestode stage of the tapeworm Echinococcus granulosus by assessing the viability, ultrastructure, and tegumental membrane potential as a function of drug concentration and incubation time. Concentrations of 0.1 and 1.0 μg/ml of IVM had no effect on any of these three parameters for up to 6 days of treatment. A concentration of 10 μg/ml, however, elicited a sequence of alterations that started with a ∼20-mV depolarization of the tegumental membrane, and was followed by rostellar disorganization, rigid paralysis and, eventually, loss of viability. It is likely that the IVM-induced depolarization of the tegument acts as the signal that initiates the cascade of degenerative processes that leads to the parasite's death. This would place the tegument as the primary target of action of IVM on cestodes. As an appropriate chemotherapy for the hydatid disease is still lacking, the cestocidal effect of IVM reported here is worth considering.
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U2 - 10.1007/s004360100435
DO - 10.1007/s004360100435
M3 - Article
C2 - 11688885
AN - SCOPUS:0034814095
SN - 0932-0113
VL - 87
SP - 804
EP - 807
JO - Parasitology Research
JF - Parasitology Research
IS - 10
ER -