Resveratrol exerts in vitro anti-echinococcal activity by targeting the TOR signaling pathway in the larval stage of E. granulosus.

LOOS JULIA .A.; RETTA KAREN; PAVIA NATALIA; LEDO CAMILA; CUMINO ANDREA C

Salta

Congreso; IX Congreso Argentino de Parasitología; 2022

Asociación Parasitológica Argentina

RESVERATROL EXERTS IN VITRO ANTI-ECHINOCOCCAL ACTIVITY BY TARGETING THE TOR SIGNALING PATHWAY IN THE LARVAL STAGE OF ECHINOCOCCUS GRANULOSUSJulia A. Loos 1,2 ; Karen Retta 1 ; Natalia Pavía 1 ; Camila Ledo 1,2 ; Andrea C. Cumino 1,2 1National University of Mar del Plata, 2National Council of Scientific and Technical ResearchCystic echinococcosis (CE) is a neglected parasitic disease caused by the larval stage of Echinococcus granulosus for which an effective treatment is not yet available. We have previously identified three master regulators of energy metabolism in Echinococcus, AMPK, TOR and SIRT1, and demonstrated the susceptibility of the parasite to AMPK agonists and TOR inhibitors, which also showed a synergistic effect in combination with albendazol. Currently, our main goal is to contribute to the treatment of CE using new combinations of drugs that attack these pathways. Resveratrol (Rvt) is a nature-derived compound that exhibits a wide range of biological and pharmacological properties including antioxidant, anti-cancer, anti-coagulant, anti-inflammatory, and anti-aging actions. This low toxic agent may affect various signaling pathways related to cell death such as autophagy, through the SIRT1/AMPK dependent inhibition of TOR, and apoptosis. In the present study, we assessed the in vitro pharmacological effect of Rvt against the E. granulosus larval stage. The drug caused a significant dose-dependent decrease in the viability of metacestodes and led to loss of cells in their germinal layers. Furthermore, Rvt treated parasites showed a significant increase in transcriptional expression of autophagy key genes such as Eg-atg8, Eg-atg12 and Eg-tfeb. Moreover, by in toto immunolocalization assays, suppression of Eg-TOR and an increase in the punctate pattern of Eg-Atg8 were detected in the germinal layer of treated cysts. Our results suggest that Rvt may be useful as a therapeutic agent to treat cystic echinococcosis and warrant its further assessment in animal disease models. Although further studies are needed in order to thoroughly investigate the mechanism involved in the therapeutic response of the parasite to the drug, our data suggest that Rvt could play a role in the death of the parasite through pharmacological modulation of the autophagy signaling pathway.Key words: RESVERATROL; CYSTIC ECHINOCOCCOSIS; TOR; AUTOPHAGY