The Effect of Fluphenazine and Thioridazine on Toxoplasma gondii In Vivo

  • Mehrzad SARAEI Dept. of Medical Parasitology and Mycology, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran Cellular and Molecular Research Center, Qazvin University of Medical Sciences, Qazvin, Iran
  • Yosef GHADERI Dept. of Medical Parasitology and Mycology, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran
  • Tahereh MOSAVI Dept. of Medical Parasitology and Mycology, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran
  • Mojtaba SHAHNAZI Dept. of Medical Parasitology and Mycology, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran Cellular and Molecular Research Center, Qazvin University of Medical Sciences, Qazvin, Iran
  • Marjan NASSIRI-ASL Cellular and Molecular Research Center, Qazvin University of Medical Sciences, Qazvin, Iran Dept. of Pharmacology, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran
  • Hassan JAHANIHASHEMI Dept. of Community Medicine, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran
Keywords: Toxoplama gondii, Fluphenazine, Thioridazine, Brain cysts, In vivo

Abstract

Background: Toxoplasma gondii is the most common parasite causing latent cerebral infections in human. It has been shown that some anti-psychotic drugs are able to inhibit the proliferation of the parasite in in vitro study. There is very limited data regarding the inhibitory effect of anti-psychotics on Toxoplasma in in vivo. In this study, we evaluated anti-Toxoplasma activity of fluphenazine and thioridazine drugs on T. gondii in mice.Methods: Mice were divided into six groups: Control, sesame as vehicle, thioridazine 10 mg/kg, thioridazine 20 mg/kg, fluphenazine 0.06 mg/kg and fluphenazine 0.6 mg/kg. They were inoculated intraperitoneally with brain suspension containing tissue cysts of T. gondii Tehran strain. Two months after inoculation, the number of cysts in crushed smears of mice brain were counted microscopically and considered as an indicator of anti-Toxoplasma activity. This work has conducted in Qazvin, central Iran, 2014.Results: Our study showed that fluphenazine and thioridazine could not significantly inhibit the brain cystogenesis of T. gondii in mice. However, the number of brain cysts was less at higher dose compared to lower doses for both drugs. Conclusion: Further studies need to clear the mechanism of different structure of anti-psychotic drugs on activity of Toxoplasma.

References

Daryani A, Sarvi S, Aarabi M, Mizani A, Ahmadpour E, Shokri A, et al. Seroprevalence of Toxoplasma gondii in the Iranian general population: A systematic review and meta-analysis. Acta Trop. 2014; 137: 185-194.

Jones JL, Kruszon-Moran D, Rivera HN, Price C, Wilkins PP. Toxoplasma gondii seroprevalence in the United States 2009-2010 and comparison with the past two decades. Am J Trop Med Hyg. 2014; 90(6):1135-1139.

Yolken RH, Dickerson FB, Fuller Torrey E. Toxoplasma and schizophrenia. Parasite Immunol. 2009; 31(11):706-715.

Flegr J. Influence of latent Toxoplasma infection on human personality, physiology and morphology: pros and cons of the Toxoplasma-human model in studying the manipulation hypothesis. J Exp Biol. 2013; 216 (Pt 1):127-133.

McConkey GA, Martin HL, Bristow GC, Webster JP. Toxoplasma gondii infection and behaviour - location, location, location? J Exp Biol. 2013; 216 (Pt 1):113-119.

Torrey EF, Bartko JJ, Lun ZR, Yolken RH. Antibodies to Toxoplasma gondii in patients with schizophrenia: a meta-analysis. Schizophr Bull. 2007; 33(3):729-736.

Park MH, Kwon YJ, Jeong HY, Lee HY, Hwangbo Y, Yoon HJ, et al. Association between intracellular infectious agents and schizophrenia. Clin Psychopharmacol Neurosci. 2012; 10(2):117-123.

Alipour A, Shojaee S, Mohebali M, Teh-ranidoost M, Abdi Masoleh F, Keshavarz H. Toxoplasma infection in schizophrenia patients: a comparative study with control group. Iran J Parasitol. 2011; 6(2), 31-37.

Hrdá S, Votýpka J, Kodym P, Flegr J. Transient nature of Toxoplasma gondii-induced behavioral changes in mice. J Parasitol. 2000; 86(4), 657-663.

Berdoy M, Webster JP, Macdonald DW. Fatal attraction in rats infected with Toxoplasma gondii. Proc Biol Sci. 2000; 267(1452): 1591-1594.

Webster JP, Brunton CF, MacDonald DW. Effect of Toxoplasma gondii upon neophobic behavior in wild brown rats, Rattus norvegicus. Parasitology. 1994;109(Pt 1): 37-43

Horacek J, Flegr J, Tintera J, Verebova K, Spaniel F, Novak T, et al. Latent toxoplasmosis reduces gray matter density in schizophrenia but not in controls: voxel-based-morphometry (VBM) study. World J Biol Psychiatry. 2012; 13(7):501-509.

Jones-Brando, Torrey EF, Yolken R. Drugs used in the treatment of schizophrenia and bipolar disorder inhibit the replication of Toxoplasma gondii. Schizophr Res. 2003; 62(3):237-244.

Webster JP, Lamberton PH, Donnelly CA, Torrey EF. Parasites as causative agents of human affective disorders? The impact of anti-psychotic, mood-stabilizer and anti-parasite medication on Toxoplasma gondii's ability to alter host behaviour. Proc Biol Sci. 2006; 273(1589): 1023-1030.

Goodwin DG, Strobl J, Mitchell SM, Zajac AM, Lindsay DS. Evaluation of the mood-stabilizing agent valproic acid as a preventative for toxoplasmosis in mice and activity against tissue cysts in mice. J Parasitol. 2008; 94(2):555-557.

Goodwin DG, Strobl JS, Lindsay DS. Evaluation of five antischizophrenic agents against Toxoplasma gondii in human cell cultures. J Parasitol. 2011; 97(1):148-151.

Johanson JS, Holliman RE. Toxoplasmosis. In: Gillespie SH, Hawkey PM, editors. Medical parasitology a practical approach. New York: Oxford University Press Inc; 1995, p. 33-59.

Strobl JS, Cassell M, Mitchell SM, Reilly CM, Lindsay DS. Scriptaid and suberoylanilide hydroxamic acid are histone deacetylase inhibitors with potent anti-Toxoplasma gondii activity in vitro. J Parasitol. 2007; 93(3): 694-700.

Shibre T, Alem A, Abdulahi A, Araya M, Beyero T, Medhin G, et al. Trimethoprim as adjuvant treatment in schizophrenia: a double-blind, randomized, placebo-controlled clinical trial. Schizophr Bull. 2010; 36(4): 846-851.

Dickerson FB, Stallings CR, Boronow JJ, Origoni AE, Yolken RH. A double-blind trial of adjunctive azithromycin in individuals with schizophrenia who are seropositive for Toxoplasma gondii. Schizophr Res. 2009; 112(1-3):198-199.

Carroll FI, Houghten RA. From rapid in vitro screening to rapid in vivo screening in the drug discovery process. Neuropsychopharmacology. 2009; 34(1):251-252.

Walker E, Kestler L, Bollini A, Hochman KM. Schizophrenia: Etiology and course. Annu Rev Psychol. 2004; 55:401-430.

Meltzer H. Antipsychotic Agents and Lithium. In: Katzung BG, Masters SB, Trevor AJ editors. Basic and clinical pharmacology. New York: McGraw-Hill; 2012, p. 362-383.

Vieira MC, Moreno SN. Mobilization of intracellular calcium upon attachment of Toxoplasma gondii tachyzoites to human fibroblasts is required for invasion. Mol Biochem Parasitol. 2000; 106(1):157-162.

Pezzella N, Bouchot A, Bonhomme A, Pingret L, Klein C, Burlet H, et al. Involvement of calcium and calmodulin in Toxoplasma gondii tachyzoite invasion. Eur J Cell Biol. 1997; 74(1): 92-101.

Song HO, Ahn MH, Ryu JS, Min DY, Joo KH, Lee YH. Influence of calcium ion on host cell invasion and intracellular replication by Toxoplasma gondii. Korean J Parasitol. 2004; 42(4):185-193.

Published
2016-12-21
How to Cite
1.
SARAEI M, GHADERI Y, MOSAVI T, SHAHNAZI M, NASSIRI-ASL M, JAHANIHASHEMI H. The Effect of Fluphenazine and Thioridazine on Toxoplasma gondii In Vivo. IJPA. 11(2):226-31.
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Original Article(s)