In vivo effects of metformin against Echinococcus granulosus larval stage.

LOOS JULIA A; DRAGO DANIELA*, ; MELUCCI GANZARAIN CLAUDIA*; DÁVILA VALERIA* , ; RODRÍGUEZ R. C; CUMINO ANDREA C

Mar del Plata

Congreso; LX Reunión Anual de la Sociedad Argentina de Investigación Clínica, Reunión Sociedad Argentina de Fisiología; 2015

Sociedad Argentina de Investigación Clínica,

Cystic echinococcosis is a zoonotic infection caused by the larval stage of the cestode Echinococcus granulosus. Chemotherapy currently employs benzimidazoles, however 40% of cases do not respond favorably. With regard to these difficulties, novel therapeutical tools are needed to optimize treatment in humans. The aim of this work was to explore in vivo the effect of metformin (Met) against E. granulosus, due to the fact that in vitro the drug inhibits the survival of E. granulosus protoscoleces and metacestodes. We demonstrated the chemotherapeutic and chemopreventive pharmacological effects of the drug. At a dose rate of 50 mg/kg/day, Met induces protection against the infection in mice. In the clinical efficacy studies, a reduction in cyst weight was observed after the administration of 50 mg/kg to mice with cysts developed during four months (0.54 ± 0.10 g), compared to those collected from control mice (1.75 ± 0.2 g). In vitro synergic therapeutic effects were observed in presence of Met plus albendazole (0.07 ± 0.01 g) at low doses (5mg/kg day of ABZSO), suggesting the importance of chemoprophylactic and clinical efficacy studies combining Met with conventional anti-echinococcal agents to test the potential use of this drug in hydatidosis therapy. P-glycoprotein expression was investigated and since Met was detected into murine cysts (0.2 to 0.5 μg Met/g wet weight of cyst), we analyzed the genome occurrence OCT1/OCTN1 orthologs in Echinococcus sp. We identified five putative OCT1/OCTN1 of which OCT A, B, D and E were expressed in protoscoleces and metacestodes allowing the accumulation of the drug in parasitic tissues. Possible mechanisms for the susceptibility of metformin are discussed in relation to dual metabolic control of parasite and host.