Toxoplasma gondii, which is the agent of toxoplasmosis, is an obligate intracellular protozoan that can infect a wide range of vertebrate cells. Here, we describe the cytotoxic effects of the dinuclear iron compound [Fe(HPClNOL)(SO4)]2-μ-oxo, where HPClNOL is the ligand 1-(bis-pyridin-2-ylmethyl-amino)-3-chloropropan-2-ol, on T. gondii infecting LLC-MK2 host cells. This compound was not toxic to LLC-MK2 cells at concentrations up to 200 μM but was very active against the parasite, with an IC50 of 3.6 μM after 48 h of treatment. Cyst formation was observed after treatment as indicated by the appearance of a cyst wall, Dolichos biflorus lectin staining, and scanning and transmission electron microscopy characteristics. Ultraestructural changes were also seen in T. gondii, including membrane blebs and clefts in the cytoplasm with inclusions similar to amylopectin granules, which are typically found in bradyzoites. An analysis of cell death pathways in the parasite revealed that a combination of apoptosis and autophagy was caused by the compound. Fluorescence assays demonstrated that the redox environment in the LLC-MK2 cells becomes oxidant in the presence of the iron compound. Furthermore, a reduction of superoxide dismutase and catalase activities in the treated parasites and the presence of reactive oxygen species within the parasitophorous vacuoles were observed, indicating an impaired protozoan response against these radicals. These findings suggest that this compound disturbs the redox equilibrium of T. gondii, inducing cystogenesis and parasite death.
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