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Cytotoxic effects of ivermectin on Giardia lamblia: induction of apoptosis and cell cycle arrest
Article
Authorship:
Barzola, Florencia Nicole ; Laiolo, Jerónimo ; Cotelo, Camilo ; Joray, Mariana Belén ; Volpini, Ximena ; Rivero, María Romina ; Rópolo, Andrea Silvana ; Touz, María Carolina ; FELIZIANI, CONSTANZADate:
2024Publishing House and Editing Place:
Frontiers Media S.AMagazine:
Frontiers in Microbiology, vol. 15 Frontiers Media S.ASummary *
Introduction: Giardia lamblia is a flagellated protozoan parasite causinggiardiasis, a common intestinal infection characterized by diarrhea, abdominalcramps, and nausea. Treatments employed to combat this parasitic infectionhave remained unchanged for the past 40 years, leading to the emergence ofresistant strains and prompting the search for new therapeutic agents.Methods: This study investigated the cytotoxic effects of ivermectin (IVM) onG. lamblia trophozoites. We conducted dose-response experiments to assessIVM-induced cytotoxicity. We utilized various biochemical and ultrastructuralanalyses to explore the underlying mechanisms of cell death, including reactiveoxygen species (ROS) production, DNA fragmentation, cell cycle arrest, andapoptosis markers.Results: Our findings demonstrate that IVM induces dose-dependentcytotoxicity and triggers cell death pathways. We found that IVM treatmentgenerates elevated levels of reactive oxygen species (ROS), DNA fragmentation,and arrests of trophozoites in the cell cycle’s S phase. Additionally, ultrastructuralanalysis reveals morphological alterations consistent with apoptosis, such ascytoplasmic vacuolization, chromatin condensation, and tubulin distribution.Discussion: The insights gained from this study may contribute to developingnew therapeutic strategies against giardiasis, addressing the challenge posed bydrug-resistant strains. Information provided by the agent in SIGEVAKey Words
APOPTOSISCYTOTOXICITYPARASITIC INFECTIONSIVERMECTIN