Histological demonstration of apoptosis activation in the liver fluke (Fasciola hepatica) following Closantel treatment of experimentally-infected sheep

SCARCELLA S.; SOLANA MV.; BIANCO F.; SOLANA H.; LOMBARDO D.

Congreso; XXI Reunion anual de la Sociedad Argentina de Protozoologia; 2019

Theapoptosis can be by DNA damage, cytokine expression, etc. The study of apoptosishas application for the understanding of biological events, such as the tumorogenesis,the action mechanism to drugs, etc. For the apoptosis detection in differentcell lines and tissues there are methods such as TdT-mediated dUDP nick endlabelling (TUNEL) or directly the immunolocalization of Caspase-3. Closantelis an antiparasitic halogenated salicilanilide for the treatment of Fasciola hepatica infestation in farmanimals. Its action mechanism is not fully known. It´s known decouple theoxidative phosphorylation but the probable degree of contribution of apoptosis is unknown.In this work, were used the Caspase-3detection and TUNEL techniquesto assess the probable involvement of the closantel in the generation of apoptosisin Fasciola hepatica. Fourteen lambs were infected orally with 200metacercariae of Fasciola hepatica.At 16 weeks post-infection, 10 lambs were treated orally with closantel (10mg/kg.). Adult flukes were recovered from the liver of individual lambs at 0h (notreated n:4), 24h (n:5) and 36h (n:5) post treatment. The flukes were processedfor usual histological analysis.There were noinjuries at the controls. The F. hepaticaat 24 h PT showed minor damage to the posterior end of syncytium. Those of 36 hPT lost large areas of the syncytium in the posterior and dorsal end with celldepletion in testis and vitelline follicles and the oocytes appear rounded withcondensed cytoplasm, indicating apoptosis. In testis, ovary and vitellinefollicles, defects in closantel-treated trematodes were aligned with failure inthe energy-demanding processes of mitosis and differentiation. These changescould be attributed to anthelmintic-induced blockage of intermediary metabolismand neuromuscular paralysis. This work confirm that closantel activatesapoptosis being too this phenomenon its mechanism of action