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Abstract:

Human cystic echinococcosis is a zoonosis caused by the larval stage of the tapeworm Echinococcus granulosus sensu lato (s. l.). Although benzimidazole compounds such as albendazole (ABZ) and mebendazole have been the cornerstone of chemotherapy for the disease, there is often no complete recovery after treatment. Hence, new strategies are required to improve treatment of human cystic echinococcosis. The goals of the current study were as follows: (i) to evaluate the in vitro efficacy of the 5-fluorouracil (5-FU) and ABZ combination against E. granulosus s. l. protoscoleces and cysts, (ii) to compare the clinical efficacy of 5-FU alone or in combination with ABZ in infected mice. The combination of 5-FU + ABZ had a stronger in vitro effect against larval stage than that did both drugs alone. Even at the lowest concentration of 5-FU + ABZ combination (1 μg/ml), the reduction of the viability of protoscoleces and cysts was greater than that observed with drugs alone at 10 μg/ml. The results were confirmed at the ultrastructural level by scanning electron microscopy. These data helped to justify the in vivo investigations assessing the therapeutic potential of the combination of 5-FU and ABZ suspension in CF-1 mice infected with E. granulosus sensu stricto (s. s.) metacestodes. Treatment with 5-FU (10 mg/kg) or 5-FU (10 mg/kg) + ABZ suspension (5 mg/kg) reduced the weight of cysts recovered from mice compared with control groups. Interestingly, the effect of 5-FU given weekly for 5 consecutive weeks was comparable to that observed with ABZ suspension under a daily schedule during 30 days. Co-administration of 5-FU with ABZ did not enhance the in vivo efficacy of drugs alone calculated in relation to cysts weights. However, the combination provoked greater ultrastructural alterations compared to the monotherapy. In conclusion, we demonstrated the efficacy of 5-FU either alone or co-administrated with ABZ against murine experimental cystic echinococcosis. Since 5-FU treatments did not cause toxic effect in mice, further in vivo studies will be performed by adjusting the dosage and the frequency of treatments. © 2017 Elsevier B.V.

Registro:

Documento: Artículo
Título:Experimental cystic echinococcosis therapy: In vitro and in vivo combined 5-fluorouracil/albendazole treatment
Autor:Pensel, P.E.; Elissondo, N.; Gambino, G.; Gamboa, G.U.; Benoit, J.P.; Elissondo, M.C.
Filiación:Laboratorio de Zoonosis Parasitarias, Instituto de Investigaciones en Producción, Sanidad y Ambiente (IIPROSAM), Fac. Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata, Argentina
Laboratorio de Análisis Clínicos Santisteban, 7000 Tandil, Buenos Aires, Argentina
Departamento de Farmacia, Fac. Ciencias Químicas, Universidad Nacional de Córdoba, UNITEFA, Argentina
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina
INSERM U1066, MINT–Micro et Nanomédecines biomimétiques, IBS-CHU Angers, Angers cedex 9, Angers, France
Palabras clave:5-fluorouracil; Albendazole; Cystic echinococcosis; Echinococcus granulosus sensu stricto; albendazole; fluorouracil; albendazole; fluorouracil; animal experiment; animal model; Article; concentration response; controlled study; drug efficacy; echinococcosis; Echinococcus granulosus; experimental infection; female; in vitro study; in vivo study; larval stage; metacestode; monotherapy; mouse; nonhuman; parasite viability; scanning electron microscopy; suspension; treatment response; ultrastructure; animal; combination drug therapy; dose response; echinococcosis; Albendazole; Animals; Dose-Response Relationship, Drug; Drug Therapy, Combination; Echinococcosis; Echinococcus granulosus; Female; Fluorouracil; Mice
Año:2017
Volumen:245
Página de inicio:62
Página de fin:70
DOI: http://dx.doi.org/10.1016/j.vetpar.2017.08.011
Título revista:Veterinary Parasitology
Título revista abreviado:Vet. Parasitol.
ISSN:03044017
CODEN:VPARD
CAS:albendazole, 54965-21-8; fluorouracil, 51-21-8; Albendazole; Fluorouracil
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03044017_v245_n_p62_Pensel

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Citas:

---------- APA ----------
Pensel, P.E., Elissondo, N., Gambino, G., Gamboa, G.U., Benoit, J.P. & Elissondo, M.C. (2017) . Experimental cystic echinococcosis therapy: In vitro and in vivo combined 5-fluorouracil/albendazole treatment. Veterinary Parasitology, 245, 62-70.
http://dx.doi.org/10.1016/j.vetpar.2017.08.011
---------- CHICAGO ----------
Pensel, P.E., Elissondo, N., Gambino, G., Gamboa, G.U., Benoit, J.P., Elissondo, M.C. "Experimental cystic echinococcosis therapy: In vitro and in vivo combined 5-fluorouracil/albendazole treatment" . Veterinary Parasitology 245 (2017) : 62-70.
http://dx.doi.org/10.1016/j.vetpar.2017.08.011
---------- MLA ----------
Pensel, P.E., Elissondo, N., Gambino, G., Gamboa, G.U., Benoit, J.P., Elissondo, M.C. "Experimental cystic echinococcosis therapy: In vitro and in vivo combined 5-fluorouracil/albendazole treatment" . Veterinary Parasitology, vol. 245, 2017, pp. 62-70.
http://dx.doi.org/10.1016/j.vetpar.2017.08.011
---------- VANCOUVER ----------
Pensel, P.E., Elissondo, N., Gambino, G., Gamboa, G.U., Benoit, J.P., Elissondo, M.C. Experimental cystic echinococcosis therapy: In vitro and in vivo combined 5-fluorouracil/albendazole treatment. Vet. Parasitol. 2017;245:62-70.
http://dx.doi.org/10.1016/j.vetpar.2017.08.011