Study on the effect of an ion channel inhibitor "Fluralaner" on protoscolices and metacestode layers in vitro.

Hydatid disease has a great impact on public health, causing high morbidity and mortality. Main lines of treatment include surgery, which mostly requires the installation of a scolicidal agent into hydatid cysts to prevent dissemination. Alternatively, medical treatment involves the use of benzimidazole drugs; however, the results are not satisfactory, and new drug compounds are urgently needed. Fluralaner is a potent inhibitor of GABA-gated chloride channels and L-glutamate-gated chloride channels (GluCls) providing immediate and persistent flea, tick and mite control in dogs after a single oral dose. Researches previously identified different genes encoding ion channels in , making ion channel inhibitors a promising target for treating hydatid disease. Thus, the present study aimed to evaluate the effect of fluralaner on protoscolices and metacestode layers. Parasite materials (Protoscolices, Metacestodes layers) were exposed to different concentrations of the drug ranging from "12.5-100 ug/ml" and examined for viability after 1, 6 and 24 h. Morphological and ultrastructural alterations were recorded by both light and electron microscopies. Immunohistochemical staining confirmed caspase-3 activation as an indicator of apoptosis- induced therapy. The treated protoscolices and metacestode layers showed loss of the viability, the formation of vacuoles and lipid droplets, separation of the germinal layer, and damage in the laminated layer; apoptosis was prominent after treatment. These findings revealed that fluralaner has a potent scolicidal activity and suggested its therapeutic potential against hydatid disease. Further evaluations for animals and human use in the treatment and prevention of hydatid disease are needed.