Open AccessMetformin exhibits preventive and therapeutic efficacy against experimental cystic echinococcosis
Author(s) -
Julia Loos,
Valeria A. Dávila,
Christian Rodríguez Rodrígues,
Romina Sandra Petrigh,
Jorge Zoppi,
Fernando A. Crocenzi,
Andrea C. Cumino
Publication year - 2017
Publication title -
plos neglected tropical diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.99
H-Index - 135
eISSN - 1935-2735
pISSN - 1935-2727
DOI - 10.1371/journal.pntd.0005370
Subject(s) - echinococcus granulosus , metformin , in vivo , in vitro , pharmacology , medicine , drug , echinococcosis , biology , pathology , microbiology and biotechnology , biochemistry , zoology , insulin
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.