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The effect of edelfosine on GRA1 and MIC3 expressions in acute toxoplasmosis

  • Protozoology - Original Paper
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Abstract

Phosphoinositide-dependent phospholipase-C (PI-PLC) triggers the calcium signaling pathway which plays an important role in dense granule and microneme secretion and pathogenesis of Toxoplasma gondii (T. gondii). There are limited data about the effects of phospholipid analogues against T. gondii. The current study assessed the effect of edelfosine, as a phospholipid analogue, on GRA1 and MIC3 expressions using in vitro and in vivo models of acute toxoplasmosis. Infected Vero cells were treated by edelfosine in two subgroups: 24 h following the cell infection and treatment at the same time of cell infection. Animal study was performed on forty mice in four groups including non-infected, infected untreated, infected edelfosine-treated, and infected pyrimethamine-treated. Gene and protein expression analyses were done using quantitative real-time PCR and western blot, respectively. Edelfosine significantly reduced the GRA1 (P < 0.01) and MIC3 (P < 0.01) mRNA and protein expressions in 24 h following the cell infection and at the same time of cell infection groups. In vivo study showed that the edelfosine significantly reduced the GRA1 expression in eye, and MIC3 expression in brain and liver. Moreover, the edelfosine-treated infected mice had significant higher survival rate compared with uninfected mice. The reducing effect of edelfosine on GRA1 and MIC3 mRNA and protein levels 24 h following the cell infection was more than treatment at the same time of cell infection group. Moreover, the effect of edelfosine on GRA1 and MIC3 expression in animal tissues was variable. These data showed that the edelfosine may decrease the T. gondii excretory/secretory antigens through inhibition of PI-PLC.

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Acknowledgments

We acknowledge the support by the Research Foundation of the Mazandaran University of Medical Sciences. Authors have a special appreciation to Dr. Amir Azimian for the primer design.

Funding

This work was supported financially from the vice chancellor for research at Mazandaran University of Medical Sciences (No. 1242).

Author information

Authors and Affiliations

  1. Toxoplasma Research Center, Mazandaran University of Medical Sciences, Sari, Iran

    Asal Tanzifi, Shahabeddin Sarvi, Mehdi Sharif, Mahbobeh Montazeri & Ahmad Daryani

  2. Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran

    Asal Tanzifi & Mahbobeh Montazeri

  3. Department of Parasitology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

    Asal Tanzifi, Shahabeddin Sarvi, Mahbobeh Montazeri & Ahmad Daryani

  4. Deparment of Clinical Biochemistry, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran

    Amirhosein Khoshi

  5. Department of Medical Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran

    Saeed Emami

  6. Department of Parasitology, Faculty of Medicine, Sari Branch, Islamic AZAD University, Sari, Iran

    Mehdi Sharif

  7. Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Meysam Moghbeli

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  1. Asal Tanzifi
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  8. Ahmad Daryani
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Contributions

AT performed the cellular, animal, laboratory, and molecular testing. AK designed the study and supervised the molecular testing. SE advised selection of concentrations in cellular and animal studies. SS and MS supervised the animal study. MM collaborated in cellular testing. MM collaborated in final manuscript edition. AD designed and supervised the laboratory testing.

Corresponding author

Correspondence to Ahmad Daryani.

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The authors declare that they have no conflict of interest.

Ethics statement

This study was carried out in accordance with the recommendations of Ethics commission of the Mazandaran University of Medical Sciences. The protocol was approved by the ethics committee of Mazandaran University of Medical Sciences (Project ethic number: IR.MAZUMS.REC.1397.1242).

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Tanzifi, A., Khoshi, A., Emami, S. et al. The effect of edelfosine on GRA1 and MIC3 expressions in acute toxoplasmosis. Parasitol Res 119, 1371–1380 (2020). https://doi.org/10.1007/s00436-020-06601-x

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  • DOI: https://doi.org/10.1007/s00436-020-06601-x

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