In vivo and in vitro efficacies of glibenclamide treatment against cyst echinococcosis

VALERIA DÁVILA; CLAUDIA MELUCCI GANZARAIN; DANIELA DRAGO; JULIA A. LOOS; CHRISTIAN RODRIGUES RODRIGUEZ; ANDREA C. CUMINO

Buenos Aires

Congreso; XXVII Reunión Anual de la Sociedad Argentina de Protozoología; 2015

Sociedad Argentina de Protozoología

Cystic echinococcosis or hydatidosis is a widely endemic infection caused by the larval stage of E. granulosus, which produces clinical disease in humans and economic losses to the livestock industry. In this work we demonstrate that glibenclamice (Gli) inhibit viability in vitro of the Echinococcus protoscoleces and cysts, in a dose-dependent manner. After 15 days of incubation with 200μM Gli the viability of treated protoscoleces was reduced to 45 ± 5% whereas a 2-days treatment against in vitro cultures of cyst resulted in detachment of the germinal layers. Ultrastructural damages appeared earlier than the viability inhibition with low drug concentrations. In addition, on Gli-treated protoscoleces it was observed an increase in the intracellular Ca2+ concentration, the level of acidic vesicles and LC3II expression and key genes of the autophagic pathway (atg6, atg8, atg12 and atg18). Oral application of Gli (5 mg/kg of body weight administered daily) for a period of 8 weeks in E. ganulosus-infected mice was effective in achieving reduction of parasite weight (0.23 ± 0.08 g) in respect to the control treatment (1.9 ± 0.6 g) and the albendazole-treated mice (0.9 ± 0.1 g of cyst weight with 5 mg/kg/day of drug). However, combined application of both drugs (Gli plus albendazole) did not increase the treatment efficacy, and the reduction in parasite weight was lower than when treated with albendazole alone, but higher than with Gli only. Our data clearly demonstrated a cytostatic effect of Gli in clinical efficacy studies that may be mediated through KATP channels and/or associated to the inhibition of the G1-S phase progression.