Coalism effect of combination therapy with metformin and a suboptimal dose of albendazole in experimental alveolar echinococcosis.

LOOS JULIA .A.; PAVIA NATALIA; COCCIMIGLIO MAGALÍ; CUMINO ANDREA C

Singapur

Conferencia; 9th International Conference of Parasitology & Microbes; 2021

Coalism effect of combination therapy with metformin and a suboptimal dose of albendazole in experimental alveolar echinococcosisLoos Julia A., Retta K., Pavia N., Coccimiglio M., Cumino A.IIPROSAM, Conicet, National University of Mar del Plata, Argentina. julialoos@hotmail.com Alveolar echinococcosis (AE) is a severe parasitic disease caused by the larval stage of Echinococcus multilocularis. Its current chemotherapeutic treatment is based on the long-term use of benzimidazoles, which are rarely curative and cause several adverse effects, often leading to treatment discontinuation. Therefore, it is necessary to develop alternative and safer chemotherapeutic strategies against AE. We have previously shown that metformin (Met), an anti-hyperglycemic and anti-proliferative agent that is also effective against several pathogens, exhibits considerable in vivo activity on an early-infection model of AE when administered at 50 mg/kg/day for 8 weeks. Here, we extend the study and assess the efficacy of Met alone or in combination with a low dose of albendazole (ABZ) after increasing the challenge by doubling the parasite inoculum to 400 ul or starting the treatments six weeks post infection. In both cases, only the combination of Met (100 mg/kg/day) together with a sub-optimal dose of ABZ (5 mg/kg/day) led to a significant reduction in parasite weight compared to the untreated group. Coincidentally, at the ultrastructural level, the combination of drugs showed the maximum level of damage. Likewise, Met alone or combined with ABZ led to a decrease in the availability of glucose for the parasite, which was evidenced as a lower intracystic glucose concentration in the animals of these groups. Moreover, the combination of 10 mM Met with 3 μM albendazole sulfoxide (the main active metabolite of ABZ) showed an enhanced in vitro activity on protoscolex viability as compared to each drug alone, especially at physiological glucose concentrations. Finally, the regrowth of in vitro-treated metacestode tissue in mice indicated that, despite attenuating the parasite growth, Met is not capable of exerting a true parasiticidal effect. In summary, our results demonstrate that combination therapy with Met and ABZ offers the opportunity to improve the efficacy and reduce the toxicity of AE treatment with the high-dose ABZ monotherapy. However, as the doses used in this study were low, our results also highlight the potential advantages of identifying a more effective and still safe dose combination by increasing the doses of the drugs.BiographyJulia A Loos has a PhD in Biological Science (National University of Mar del Plata, 2017) and she is currently working as an Assistant Research under the direction of Prof. Dr. Andrea Cumino. She has been serving as assistant teacher for subjects such as Histology, General Microbiology and Farmacology, that are part of the Biology, Biochemistry and Medicine courses of study. She participates in several research projects on Parasitology and has published original articles (14). Currently, her research is focused on the study of intermediary metabolism and energy control in the larval stage of Echinococcus sp.Email: julialoos@hotmail.com, acumino@gmail.comPresenting author detailsFull name: Julia A. LoosContact number: +54 9 223 4752426 Int 223Twitter account: -Linked In account: -Session name/ number: Therapeutic Parasitology.Category: Poster presentationFor queries please contact at Email: parasitology@asiaconvention.com•General : 0044-2033180199•Toll Free Number : 0800-014-8923•35 Ruddlesway, Windsor, Berkshire, SL4 5SF•For any registration queries and other payment methods like bank transfers and PayPal feel free to reach us finance@conferenceseries.com