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Metformin improves the therapeutic efficacy of low-dose albendazole against experimental alveolar echinococcosis

Published online by Cambridge University Press:  20 October 2021

Julia A. Loos ,
Magalí Coccimiglio ,
María Celeste Nicolao ,
Christian Rodriguez Rodrigues  and
Andrea C. Cumino Open the ORCID record for Andrea C. Cumino [Opens in a new window]
Julia A. Loos
Affiliation:
Laboratorio de Zoonosis Parasitarias, IIPROSAM, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata (UNMdP), Funes 3350, Nivel Cero, (7600) Mar del Plata, Argentina Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina
Magalí Coccimiglio
Affiliation:
Laboratorio de Zoonosis Parasitarias, IIPROSAM, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata (UNMdP), Funes 3350, Nivel Cero, (7600) Mar del Plata, Argentina
María Celeste Nicolao
Affiliation:
Laboratorio de Zoonosis Parasitarias, IIPROSAM, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata (UNMdP), Funes 3350, Nivel Cero, (7600) Mar del Plata, Argentina Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina
Christian Rodriguez Rodrigues
Affiliation:
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina Departamento de Química, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata (UNMdP), Funes 3350, Nivel 2, (7600) Mar del Plata, Argentina
Andrea C. Cumino*
Affiliation:
Laboratorio de Zoonosis Parasitarias, IIPROSAM, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata (UNMdP), Funes 3350, Nivel Cero, (7600) Mar del Plata, Argentina Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina Departamento de Química, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata (UNMdP), Funes 3350, Nivel 2, (7600) Mar del Plata, Argentina
*
Author for correspondence: Andrea C. Cumino, E-mail: acumino@gmail.com
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Abstract

Alveolar echinococcosis (AE) is a severe disease caused by Echinococcus multilocularis. Its chemotherapeutic treatment is based on benzimidazoles, which are rarely curative and cause several adverse effects. Therefore, it is necessary to develop alternative and safer chemotherapeutic strategies against AE. It has previously been shown that metformin (Met) exhibits considerable in vivo activity on an early-infection model of AE when administered at 50 mg kg−1 day−1 for 8 weeks. Here, the challenge is heightened by a 2-fold increase in parasite inoculum or by starting the treatment 6 weeks post-infection. In both cases, only the combination of Met (100 mg kg−1 day−1) together with a sub-optimal dose of albendazole (ABZ) (5 mg kg−1 day−1) led to a significant reduction in parasite weight compared to the untreated group. Coincidentally, drug combination showed the highest level of damage in E. multilocularis metacestodes. Likewise, Met alone or combined with ABZ led to a decrease in parasite glucose availability, which was evidenced as a lower intracystic glucose concentration. Therefore, the results demonstrate that combination therapy with Met and ABZ offers an alternative to improve the efficacy and reduce the toxicity of the high-dose ABZ monotherapy currently employed.

Keywords

Albendazolealveolar echinococcosisin vivo combination treatmentmetformin
Type
Research Article
Information
Parasitology , Volume 149 , Issue 1 , January 2022 , pp. 138 - 144
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Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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