In vitro effect of 5-fluorouracil and paclitaxel on the metacestode Echinococcus granulosus

P.E. PENSEL; C. ALBANI; G. ULLIO GAMBOA; J.P. BENOIT; M.C. ELISSONDO

ACTA TROPICA

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2014 vol. 140 p. 1 - 9

0001-706X

Human cystic echinococcosis is a zoonosis caused by the metacestode stage of the tapeworm Echinococcusgranulosus. Although benzimidazole compounds such as albendazole and mebendazole have been thecornerstone of chemotherapy for the disease, there is often no complete recovery after treatment. Hence,in searching for novel treatment options, we examined the in vitro efficacies of 5-fluorouracil (5-FU) andpaclitaxel (PTX) against E. granulosus germinal cells, protoscoleces and cysts. 5-FU or PTX inhibited thegrowth of E. granulosus cells in a time dependent manner. Although both treatments had a protoscolicidaleffect, 5-FU had a considerably stronger effect than PTX. 5-FU produced a dose- and time-dependenteffect, provoking the complete loss of viability after 24 days of incubation. Moreover, cysts did not developfollowing the inoculation of treated protoscoleces into mice. The loss of viability was slower in PTX treatedprotoscoleces, reaching to approximately 60% after 30 days. The results of the in vitro treatment with 5-FU and PTX were similar in secondary murine cysts. The employment of SEM and TEM allowed us toexamine, at an ultrastructural level, the effects induced by 5-FU and PTX on E. granulosus germinal cells,protoscoleces and murine cysts. In conclusion, the data obtained clearly demonstrated that 5-FU and PTXat clinically achievable concentrations inhibit the survival of larval cells, protoscoleces and metacestodes.In vivo studies to test the antiparasitic activities of 5-FU and PTX are currently being undertaken on themurine model of cystic echinococcosis.