Journal of Parasitic Diseases

, Volume 40, Issue 3, pp 1001–1005 | Cite as

The inhibitory effect of cromolyn sodium and ketotifen on Toxoplasma gondii entrance into host cells in vitro and in vivo

  • Fatemeh Rezaei
  • Mohammad Ali Ebrahimzadeh
  • Ahmad Daryani
  • Mehdi Sharif
  • Ehsan AhmadpourEmail author
  • Shahabeddin Sarvi
Original Article


Toxoplasma gondii is a protozoan with worldwide distribution and in spite of increasing information about its biology, treatment of toxoplasmosis is restricted to a few drugs and unfortunately using of each of drugs is associated with significant side effects in patients. This study was designed to evaluate the efficacy of cromolyn sodium and ketotifen as alternative drugs for the treatment of toxoplasmosis. In vitro; in case group, concentrations of 1, 5, 10 and 15 µg/ml of ketotifen and cromolyn sodium were added to RPMI medium containing peritoneal macrophages. After 1 h incubation and adding tachyzoites to medium, efficacy rate of these drugs in entrance inhibition of Toxoplasma tachyzoites into macrophages were evaluated after 30 and 60 min. In vivo; case groups received ketotifen and cromolyn sodium with different concentrations at various times. Control groups received none of drugs. We found that in vitro; after 60 min the best efficacy of these drugs in inhibition of cell entrance of Toxoplasma was observed at 15 µg/ml (78.9 ± 1.70 and 91.97 ± 0.37 %, respectively) (P < 0.05). In vivo; after 60 min ketotifen at 2 mg/kg in 3 h before tachyzoite injection (69.83 ± 2.25 %), and cromolyn sodium, at 10 mg/kg in 6 h before tachyzoite injection (80.47 ± 2/49 %) had the best effect on inhibition of Toxoplasma entry into the cells (P < 0.05). Our findings show that ketotifen and cromolyn sodium are suitable drugs for entrance inhibition of tachyzoites into nucleated cells in vitro and in vivo.


Toxoplasma gondii Ketotifen Cromolyn sodium Entrance inhibition Nucleated cells Mouse 



We acknowledge the financial support of Grant No. 91-234 from the Mazandaran University of Medical Science, Iran.

Conflict of interest

The authors have no conflicts of interest regarding the content of this article.


  1. Ambroise-Thomas P, Pelloux H (1993) Toxoplasmosis—congenital and in immunocompromised patients: a parallel. Parasitol Today 9:61–63CrossRefPubMedGoogle Scholar
  2. Araujo FG, Remington JS (1992) Recent advances in the search for new drugs for treatment of toxoplasmosis. Int J Antimicrob Agents 1:153–164CrossRefPubMedGoogle Scholar
  3. Chan MMY, Triemer RE, Fong D (1991) Effect of the anti-microtubule drug oryzalin on growth and differentiation of the parasitic protozoan Leishmania mexicana. Differentiation 46:15–21CrossRefPubMedGoogle Scholar
  4. Clarke M, Spudich JA (1977) Non muscle contractile proteins: the role of actin and myosin in cell motility and shape determination. Annu Rev Biochem 46:797–822CrossRefPubMedGoogle Scholar
  5. Cortez E, Stumbo AC, Saldanha-Gama R et al (2008) Immunolocalization of an osteopontin-like protein in dense granules of Toxoplasma gondii tachyzoites and its association with the parasitophorous vacuole. Micron 39:25–31CrossRefPubMedGoogle Scholar
  6. Dadimoghaddam Y, Daryani A, Sharif M, Ahmadpour E, Hossienikhah Z (2014) Tissue tropism and parasite burden of Toxoplasma gondii RH strain in experimentally infected mice. Asian Pac J Trop Med 7(7):521–524CrossRefPubMedGoogle Scholar
  7. D’Angelo JG, Bordon C, Posner GH, Yolken R, Jones-Brando L (2009) Artemisinin derivatives inhibit Toxoplasma gondii in vitro at multiple steps in the lytic cycle. J Antimicrob Chemother 63:146–150CrossRefPubMedGoogle Scholar
  8. Dubey JP (2008) The history of Toxoplasma gondii the first 100 years. J Eukaryot Microbiol 55:467–475CrossRefGoogle Scholar
  9. Ho-Yen DO, Joss AWL (1992) Human toxoplasmosis. Oxford University Press, New YorkGoogle Scholar
  10. Iaccheri B, Fiore T, Papadaki T et al (2008) Adverse drug reactions to treatments for ocular toxoplasmosis: a retrospective chart review. Clin Ther 30:2069–2074CrossRefPubMedGoogle Scholar
  11. Kaidoh T, Nath J, Fujioka H et al (1995) Effect and localization of trifluralin in Plasmodium falciparum gametocytes: an electron microscopic study. J Eukaryot Microbiol 42:61–64CrossRefPubMedGoogle Scholar
  12. Kasper LH, Mineo JR (1994) Attachment and invasion of host cells by Toxoplasma gondii. Parasitol Today 10:184–188CrossRefPubMedGoogle Scholar
  13. Morejohn LC, Bureau TE, Mole-Bajer J et al (1987) Oryzalin, a dinitroaniline herbicide, binds to plant tubulin and inhibits microtubule polymerization in vitro. Planta 172:252–264CrossRefPubMedGoogle Scholar
  14. Morisaki JH, Heuser JE, Sibley LD (1995) Invasion of Toxoplasma gondii occurs by active penetration of the host cell. J Cell Sci 108:2457–2464PubMedGoogle Scholar
  15. Nam HW, Kim DJ, Park SK et al (1993) Inhibition of entry of Toxoplasma gondii into MDCK cells by fetal bovine serum. Korean J Parasitol 31:379–382CrossRefPubMedGoogle Scholar
  16. Nath J, Okoye V, Schneider I (1994) Anti-malarial effects of the anti-tubulin herbicide trifluralin: studies with Plasmodium falciparum. DTIC documentGoogle Scholar
  17. Nichols BA, Chiappino ML (1987) Cytoskeleton of Toxoplasma gondii. J Eukaryot Microbiol 34:217–226Google Scholar
  18. Parshikov IA, Miriyala B, Muraleedharan KM et al (2005) Biocatalysis of the antimalarial artemisinin by Mucor ramannianus strains. Pharm Biol 43:579–582CrossRefGoogle Scholar
  19. Petersen E (2007) Toxoplasmosis. Semin Fetal Neonatal Med 12:214–223CrossRefPubMedGoogle Scholar
  20. Ryning FW, Remington JS (1978) Effect of cytochalasin D on Toxoplasma gondii cell entry. Infect Immun 20:739–743PubMedPubMedCentralGoogle Scholar
  21. Serranti D, Buonsenso D, Valentini P (2011) Congenital toxoplasmosis treatment. Eur Rev Med Pharmacol Sci 15:193–198PubMedGoogle Scholar
  22. Stokkermans TJW, Schwartzman JD, Keenan K et al (1996) Inhibition of Toxoplasma gondii replication by dinitroaniline herbicides. Exp Parasitol 84:355–370CrossRefPubMedGoogle Scholar
  23. Van der Ven AJAM, Schoondermark-van de Ven EME, Camps W et al (1996) Anti-Toxoplasma effect of pyrimethamine, trimethoprim and sulphonamides alone and in combination: implications for therapy. J Antimicrob Chemother 38:75–80CrossRefPubMedGoogle Scholar
  24. Weiss LM, Kim K (2004) Toxoplasma gondii: the model apicomplexan. Perspectives and methods. Academic Press, LondonGoogle Scholar

Copyright information

© Indian Society for Parasitology 2014

Authors and Affiliations

  • Fatemeh Rezaei
    • 1
  • Mohammad Ali Ebrahimzadeh
    • 2
  • Ahmad Daryani
    • 1
    • 3
  • Mehdi Sharif
    • 1
    • 3
  • Ehsan Ahmadpour
    • 1
    • 4
    Email author
  • Shahabeddin Sarvi
    • 1
    • 3
  1. 1.Toxoplasmosis Research CenterMazandaran University of Medical SciencesSariIran
  2. 2.Pharmaceutical Sciences Research Center, School of PharmacyMazandaran University of Medical SciencesSariIran
  3. 3.Parasitology and Mycology Department, Sari Medical SchoolMazandaran University of Medical SciencesSariIran
  4. 4.Infectious and Tropical Diseases Research CenterTabriz University of Medical SciencesTabrizIran

Personalised recommendations