Metformin exhibits preventive and therapeutic efficacy against experimental cystic echinococcosis.
Metformin (Met) is an anti-hyperglycemic and potential anti-cancer agent which may exert its anti-proliferative effects via the induction of energetic stress. In this study we investigated the in vitro and in vivo efficacy of Met against the larval stage of Echinococcus granulosus. Metformin showed significant dose- and time-dependent killing effects on in vitro cultured protoscoleces and metacestodes. Notably, the combination of Met together with the minimum effective concentration of ABZSO had a synergistic effect after days 3 and 12 on metacestodes and protoscoleces, respectively. Oral administration of Met (50 mg/kg/day) in E. granulosus-infected mice was highly effective in reducing the weight and number of parasite cysts, yet its combination with the lowest recommended dose of ABZ (5 mg/kg/day) was even more effective. Coincidentally, intracystic Met accumulation was higher in animals treated with both drugs compared to those administered Met alone. Furthermore, the safe plant-derived drug Met exhibited remarkable chemopreventive properties against secondary hydatidosis in mice. In conclusion, based on our experimental data, Met emerges as a promising anti-echinococcal drug as it has proven to efficiently inhibit the development and growth of the E. granulosus larval stage and its combination with ABZ may improve the current anti-parasitic therapy.
Laboratorio de Zoonosis Parasitarias, Departamento de Biología, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata (UNMdP), Funes 3350, Nivel Cero, Mar del Plata, Argentina.|Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Julia A
JA
Loos
Laboratorio de Zoonosis Parasitarias, Departamento de Biología, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata (UNMdP), Funes 3350, Nivel Cero, Mar del Plata, Argentina.|Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Valeria A
VA
Dávila
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.|Departamento de Química, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata (UNMdP), Funes 3350, Nivel 2, Mar del Plata, Argentina.
Christian R
CR
Rodrígues
Laboratorio de Zoonosis Parasitarias, Departamento de Biología, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata (UNMdP), Funes 3350, Nivel Cero, Mar del Plata, Argentina.|Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Romina
R
Petrigh
Servicio de Patología, Hospital Privado de Comunidad (HPC), Córdoba 4545, Nivel 3, Mar del Plata, Argentina.
Jorge A
JA
Zoppi
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.|Instituto de Fisiología Experimental (IFISE), Universidad Nacional de Rosario (UNR), Suipacha 570, Rosario, Argentina.
Fernando A
FA
Crocenzi
Laboratorio de Zoonosis Parasitarias, Departamento de Biología, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata (UNMdP), Funes 3350, Nivel Cero, Mar del Plata, Argentina.|Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.|Departamento de Química, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata (UNMdP), Funes 3350, Nivel 2, Mar del Plata, Argentina.
Andrea C
AC
Cumino
D000284:Administration, Oral; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage* / Q000494:pharmacology*; D018890:Chemoprevention / Q000379:methods; D004195:Disease Models, Animal; D004357:Drug Synergism; D004443:Echinococcosis / Q000188:drug therapy* / Q000517:prevention & control*; D048209:Echinococcus granulosus / Q000187:drug effects*; D007814:Larva / Q000187:drug effects; D008687:Metformin / Q000008:administration & dosage* / Q000494:pharmacology*; D051379:Mice; D016019:Survival Analysis; D016896:Treatment Outcome
D000871:Anthelmintics; D008687:Metformin