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

LOOS, JULIA A.; COCCIMIGLIO, MAGALÍ; NICOLAO, MARÍA CELESTE; RODRIGUEZ RODRIGUES, CHRISTIAN; CUMINO, ANDREA C.

PARASITOLOGY

CAMBRIDGE UNIV PRESS

Lugar: Cambridge; Año: 2022

0031-1820

Alveolar echinococcosis (AE) is a severe disease caused by Echinococcus multilocularis. Itschemotherapeutic treatment is based on benzimidazoles, which are rarely curative andcause 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 at50 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 untreatedgroup. 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 parasiteglucose availability, which was evidenced as a lower intracystic glucose concentration.Therefore, the results demonstrate that combination therapy with Met and ABZ offers analternative to improve the efficacy and reduce the toxicity of the high-dose ABZ monotherapycurrently employed