In vitro and in vivo effects of flubendazole on Echinococcus granulosus metacestodes

Abstract

The aim of the present work was to determine the efficacy of flubendazole (FLBZ) against Echinococcus granulosus metacestodes by using in vitro and in vivo models. Groups of 50 microcysts developed in vitro, and groups of 10 peritoneal cysts were obtained from Balb C mice with experimental secondary infections of 8 months. The cysts were placed in Leighton tubes containing 10 ml of culture medium. FLBZ was added to the medium resulting in final concentrations of 5 and 1 microg/ml for mycrocysts treatment and 10, 5, and 1 microg/ml for murine cysts treatment. In vivo treatment was performed on 20 mice that developed an experimental secondary hydatid disease over a period of 11 months. FLBZ was given (1.5 mg/kg) by the oral route once a day for 50 days. A loss of turgidity was detected in all in vitro drug treated cysts irrespective of the drug concentration or parasite origin. Inspection of treated cysts by scanning electron microscopy (SEM) revealed that the germinal layer lost it characteristic multicelular structure. These results were confirmed on the ultrastructural level by transmission electron microscopy (TEM), treated metacestodes had undergone considerable degenerative changes after the in vitro treatment. The results obtained after the in vivo treatment with FLBZ showed no significant difference between the control and treated groups related to the weight of cyst masses. However, the ultrastructural study at TEM of cysts that developed in mice from the treated group revealed alterations in the germinal layer with the presence of numerous vacuoles. With regard to the ultrastructural study at SEM, only cellular debris of the germinal layer could be seen. In conclusion, the data obtained clearly demonstrate that in vitro and in vivo treatment with FLBZ is effective against E. granulosus metacestodes.

Flubendazole and ivermectin in vitro combination therapy produces a marked effect on Echinococcus granulosus protoscoleces and metacestodes

“…MBZ, ABZ, its metabolite albendazole sulfoxide (ABZSO), and flubendazole (FLBZ) were shown to be active against protoscoleces and metacestodes of E. granulosus under in vitro and in vivo conditions (Chinnery and Morris 1986;Morris et al 1987;Pérez Serrano et al 1994, 1997Casado et al 1996;Elissondo et al 2006Elissondo et al , 2007Ceballos et al 2006). On the other hand, PZQ exhibits a high efficacy against protoscoleces and metacestodes in animal experiments (Urrea-Paris et al 1999, 2000 and it was suggested that PZQ exerts a substantial effect against metacestodes and protoscoleces when applied in combination with ABZ (Urrea-Paris et al 1999).…”

Albendazole treatment in cystic echinococcosis: pharmacokinetics and clinical efficacy of two different aqueous formulations

“…Samples of hyadatid cysts (germinal and laminated layers) were obtained from mice of each experimental group and processed as described by Elissondo et al (2007). Briefly, samples were fixed with 3% glutaraldehyde in sodium cacodylate buffer for 72 h at 4°C.…”

Chemoprophylactic Activity of Flubendazole in Cystic Echinococcosis

“…However, FLBZ has shown to induce marked in vitro damage on both protoscoleces and cysts of E. granulosus [13,15] . Moreover, a clear reduction in cyst weight was observed after the administration of FLBZ prepared as a cyclodextrin-based solution in mice with cysts developed during 3 or 9 months, compared to those collected from the untreated mice [12] .…”

“…(4) FLBZ formulation as cyclodextrin-based solutions increases its systemic bioavailability up to 25-fold in mice [16] . (5) High in vitro activity against E. granulosus protoscoleces and microcysts [12] . (6) FLBZ induces a marked weight reduction in E. granulosus cysts developed in mice [16] .…”