Apoptotic activity and anti-Toxoplasma effects of artemether on the tachyzoites and experimental infected Vero and J774 cell lines by Toxoplasma gondii

Mikaeiloo, Hajar; Ghaffarifar, Fatemeh; Dalimi, Abdolhossein; Sharifi, Zohreh; Hassan, Zuhair Mohammad

doi:10.4103/0253-7613.178838

Cited by 11 publications

(5 citation statements)

References 24 publications

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“…After KP treatment, flow cytometry analysis using Annexin-V and 7-AAD as probes showed a rapid and dose-dependent PS externalization without prominent loss of plasma membrane integrity. PS externalization without significant rupture of plasma membrane was previously observed following treatment of T. gondii with chemotherapeutic agents, using Annexin-V and either 7-AAD ( Ni Nyoman and Lüder, 2013 ) or propidium iodide ( Mikaeiloo et al, 2016 ) as probes for membrane permeabilization. The lack of increase in Annexin-V positive tachyzoites over time was also observed ( Ni Nyoman and Lüder, 2013 ).…”

Section: Discussionmentioning

confidence: 96%

Novel Activity of a Synthetic Decapeptide Against Toxoplasma gondii Tachyzoites

et al. 2018

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The killer peptide KP is a synthetic decapeptide derived from the sequence of the variable region of a recombinant yeast killer toxin-like microbicidal single-chain antibody. KP proved to exert significant activities against diverse microbial and viral pathogens through different mechanisms of action, but little is known of its effect on apicomplexan protozoa. The aim of the present study was to evaluate the in vitro activity of KP against Toxoplasma gondii, a globally widespread protozoan parasite of great medical interest. The effect of KP treatment and its potential mechanism of action on T. gondii were evaluated by various methods, including light microscopy, quantitative PCR, flow cytometry, confocal microscopy, and transmission electron microscopy. In the presence of KP, the number of T. gondii tachyzoites able to invade Vero cells and the parasite intracellular proliferation were significantly reduced. Morphological observation and analysis of apoptotic markers suggested that KP is able to trigger an apoptosis-like cell death in T. gondii. Overall, our results indicate that KP could be a promising candidate for the development of new anti-Toxoplasma drugs with a novel mechanism of action.

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Section: Discussionmentioning

confidence: 96%

Novel Activity of a Synthetic Decapeptide Against Toxoplasma gondii Tachyzoites

et al. 2018

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“…Tachyzoites were collected and washed three times with cold phosphate-buffered saline (PBS; pH 7.4) following centrifugation at 1,000 g for 10 min at 4°C. Parasite concentrations were determined by trypan blue exclusion in a hemocytometer (Neubauer) chamber and were used immediately in the experiments (Mikaeiloo et al, 2016 ).…”

Section: Methodsmentioning

confidence: 99%

Effect of Imiquimod on Tachyzoites of Toxoplasma gondii and Infected Macrophages in vitro and in BALB/c Mice

Ghaffarifar

Sharifi

Horton

et al. 2020

Front. Cell. Infect. Microbiol.

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Treatment for toxoplasmosis is not completely successful because of their unwanted side effects, and new treatments are needed. Imiquimod has ability to moderate immune response and used to treat a wide variety of infections and tumors. The aim of the present study was to evaluate the effect of imiquimod on the tachyzoites of T. gondii and infected macrophages in vitro and in BALB/c mice. The viability of T. gondii was assessed in the presence of various concentrations of imiquimod by direct counting after 6 and 24 h. The MTT assay was used to identify the viability of uninfected macrophages. The apoptotic effects were determined with flow cytometry on the tachyzoites and infected macrophages. For evaluation of parasite load in pre-treatment or post-treatment of macrophages Quantitative real time PCR (qPCR) was performed. For in vivo experiments, BALB/c mice received imiquimod before and after challenge with parasites. The mortality rate of mice, parasite numbers in spleen, and the INF-γ and IL-4 cytokine levels in spleen lymphocytes were evaluated. Imiquimod demonstrated anti-Toxoplasma effects by reducing the number of tachyzoites. The results of flow cytometry for drug-treated tachyzoites showed that apoptosis did not rise significantly relative to the control group (p < 0.05). Moreover, apoptosis was enhanced in infected macrophages as the concentration of imiquimod was reduced. The parasitic burden in imiquimod pretreated macrophages was significantly lower than those treated after infection (p < 0.01). A marked reduction was observed in survival rate, parasite load and INF-γ level in BALB/c mice that received imiquimod before parasitic challenge relative to those received drug after parasitic challenge (p < 0.01). Overall, imiquimod in the pretreated group had greater anti-Toxoplasma effects than imiquimod in posttreated group in vitro and in vivo. imiquimod may be considered as a candidate for use against Toxoplasmosis both therapeutically and prophylactically.

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“…This advantage has a genuine pharmaceutical potential, as the underlying principle may be extended to other organs and to various parasitic diseases, including toxoplasmosis (Sordet, Aumjaud, Fessi, & Derouin, 1998), Chagas disease (De Mello et al, 2016), leishmaniasis (Chaurasia et al, 2015), and malaria (Mosqueira et al, 2004; Souza et al, 2018). It is worth noting that the therapeutic potential of artemether goes far beyond the framework of malaria, as this drug also shows promise for to treating leishmaniasis (Mortazavi Dehkordi, Ghaffarifar, Mohammad Hassan, & Esavand Heydari, 2013), schistosomiasis (El‐Beshbishi et al, 2013), toxoplasmosis (Mikaeiloo, Ghaffarifar, Dalimi, Sharifi, & Hassan, 2016), and cancer, with fewer adverse effects than conventional chemotherapy (Alcântara et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of artemether toxicity on single cardiomyocytes and protective effect of nanoencapsulation

Souza

Grabe‐Guimarães

Cruz

et al. 2020

British J Pharmacology

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Background and Purpose The artemisinin derivative, artemether, has antimalarial activity with potential neurotoxic and cardiotoxic effects. Artemether in nanocapsules (NC‐ATM) is more efficient than free artemether for reducing parasitaemia and increasing survival of Plasmodium berghei‐infected mice. NCs also prevent prolongation of the QT interval of the ECG. Here, we assessed cellular cardiotoxicity of artemether and how this toxicity was prevented by nanoencapsulation. Experimental Approach Mice were treated with NC‐ATM orally (120 mg·kg−1 twice daily) for 4 days. Other mice received free artemether, blank NCs, and vehicle for comparison. We measured single‐cell contraction, intracellular Ca2+ transient using fluorescent Indo‐1AM Ca2+ dye, and electrical activity using the patch‐clamp technique in freshly isolated left ventricular myocytes. The acute effect of free artemether was also tested on cardiomyocytes of untreated animals. Key Results Artemether prolonged action potentials (AP) upon acute exposure (at 0.1, 1, and 10 μM) of cardiomyocytes from untreated mice or after in vivo treatment. This prolongation was unrelated to blockade of K+ currents, increased Ca2+ currents or promotion of a sustained Na+ current. AP lengthening was abolished by the NCX inhibitor SEA‐0400. Artemether promoted irregular Ca2+ transients during pacing and spontaneous Ca2+ events during resting periods. NC‐ATM prevented all effects. Blank NCs had no effects compared with vehicle. Conclusion and Implications Artemether induced NCX‐dependent AP lengthening (explaining QTc prolongation) and disrupted Ca2+ handling, both effects increasing pro‐arrhythmogenic risks. NCs prevented these adverse effects, providing a safe alternative to the use of artemether alone, especially to treat malaria.

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Apoptotic activity and anti-Toxoplasma effects of artemether on the tachyzoites and experimental infected Vero and J774 cell lines by Toxoplasma gondii

Cited by 11 publications

References 24 publications

Novel Activity of a Synthetic Decapeptide Against Toxoplasma gondii Tachyzoites

Novel Activity of a Synthetic Decapeptide Against Toxoplasma gondii Tachyzoites

Effect of Imiquimod on Tachyzoites of Toxoplasma gondii and Infected Macrophages in vitro and in BALB/c Mice

Mechanisms of artemether toxicity on single cardiomyocytes and protective effect of nanoencapsulation

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