Abstract |
Toxoplasma gondii, the causative 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(HPCINOL)(SO4)]2-μ-oxo, in which HPCINOL 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 of up to 200 μM but was very active against the parasite, with a 50% inhibitory concentration (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. Ultrastructural 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 the cell death pathways in the parasite revealed that the compound caused a combination of apoptosis and autophagy. Fluorescence assays demonstrated that the redox environment in the LLC-MK2 cells becomes oxidant in the presence of the iron compound. Furthermore, a reduction in 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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Authors | J A Portes, T G Souza, T A T dos Santos, L L R da Silva, T P Ribeiro, M D Pereira, A Horn Jr, C Fernandes, R A DaMatta, W de Souza, S H Seabra |
Journal | Antimicrobial agents and chemotherapy
(Antimicrob Agents Chemother)
Vol. 59
Issue 12
Pg. 7374-86
(Dec 2015)
ISSN: 1098-6596 [Electronic] United States |
PMID | 26392498
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015, American Society for Microbiology. All Rights Reserved. |
Chemical References |
- (Fe(HPCINOL)(SO4))2-mu-oxo
- Antioxidants
- Coccidiostats
- Enzyme Inhibitors
- Ferric Compounds
- Reactive Oxygen Species
- Catalase
- Superoxide Dismutase
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Topics |
- Animals
- Antioxidants
(metabolism)
- Catalase
(antagonists & inhibitors, metabolism)
- Cell Line
- Coccidiostats
(chemistry, pharmacology)
- Enzyme Inhibitors
(chemistry, pharmacology)
- Ferric Compounds
(chemistry, pharmacology)
- Macaca mulatta
- Microscopy, Electron, Transmission
- Reactive Oxygen Species
(metabolism)
- Superoxide Dismutase
(antagonists & inhibitors, metabolism)
- Toxoplasma
(drug effects, growth & development, metabolism)
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