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...

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Main Authors: Julia A Loos, Valeria A Dávila, Christian R Rodrígues, Romina Petrigh, Jorge A Zoppi, Fernando A Crocenzi, Andrea C Cumino
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-02-01
Series:PLoS Neglected Tropical Diseases
Online Access:http://europepmc.org/articles/PMC5321462?pdf=render
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spelling doaj-b9ee9b3b442b4a5bb90fa9087c00c8132020-11-25T00:59:17ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352017-02-01112e000537010.1371/journal.pntd.0005370Metformin exhibits preventive and therapeutic efficacy against experimental cystic echinococcosis.Julia A LoosValeria A DávilaChristian R RodríguesRomina PetrighJorge A ZoppiFernando A CrocenziAndrea C CuminoMetformin (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.http://europepmc.org/articles/PMC5321462?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Julia A Loos
Valeria A Dávila
Christian R Rodrígues
Romina Petrigh
Jorge A Zoppi
Fernando A Crocenzi
Andrea C Cumino
spellingShingle Julia A Loos
Valeria A Dávila
Christian R Rodrígues
Romina Petrigh
Jorge A Zoppi
Fernando A Crocenzi
Andrea C Cumino
Metformin exhibits preventive and therapeutic efficacy against experimental cystic echinococcosis.
PLoS Neglected Tropical Diseases
author_facet Julia A Loos
Valeria A Dávila
Christian R Rodrígues
Romina Petrigh
Jorge A Zoppi
Fernando A Crocenzi
Andrea C Cumino
author_sort Julia A Loos
title Metformin exhibits preventive and therapeutic efficacy against experimental cystic echinococcosis.
title_short Metformin exhibits preventive and therapeutic efficacy against experimental cystic echinococcosis.
title_full Metformin exhibits preventive and therapeutic efficacy against experimental cystic echinococcosis.
title_fullStr Metformin exhibits preventive and therapeutic efficacy against experimental cystic echinococcosis.
title_full_unstemmed Metformin exhibits preventive and therapeutic efficacy against experimental cystic echinococcosis.
title_sort metformin exhibits preventive and therapeutic efficacy against experimental cystic echinococcosis.
publisher Public Library of Science (PLoS)
series PLoS Neglected Tropical Diseases
issn 1935-2727
1935-2735
publishDate 2017-02-01
description 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.
url http://europepmc.org/articles/PMC5321462?pdf=render
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