Morphological and Functional Effects of Cytoskeletal and Ion-Channel Agents on the Protoscolex of Echinococcus granulosus sensu lato

Abstract

Helminthiases remain a major global health burden, and limitations of current anthelmintic therapies highlight the need for new pharmacological targets. In this study, we examined the effects of ion channel and cytoskeletal modulators on bovine lung protoscoleces (PSCs) of Echinococcus granulosus sensu lato. Compounds acting on ion channels (praziquantel, amiloride, and amlodipine) and cytoskeletal components (albendazole and cytochalasin D) were evaluated using a semi-automated motility assay, methylene blue exclusion to assess viability, and scanning electron microscopy (SEM) to characterize structural damage. All compounds produced concentration-dependent reductions in motility. Amlodipine was the most potent inhibitor of motility, whereas praziquantel and cytochalasin D produced pronounced tegumental alterations. Amiloride was the least potent compound at both endpoints and produced the mildest ultrastructural lesions. In all cases, movement was abolished at concentrations well below those required to reduce viability. Once their shared dependence on concentration was accounted for, the association between the two endpoints disappeared, indicating that paralysis and loss of viability are largely distinct responses. Motility did not recover in any compound after 24 h of drug washout. SEM analysis revealed extensive tegumental collapse, surface erosion and microtrichial loss in PSCs exposed to cytoskeletal and calcium-modulating agents. These findings highlight cytoskeletal organization and calcium-dependent ion fluxes as key physiological vulnerabilities in E. granulosus.