Abstract
BackgroundStandard treatment of toxoplasmosis is accompanied by severe side effects and low tolerability; accordingly, alternative medicines are critically needed. Ketotifen (KET) as a cell membrane stabilizer could be an appropriate inhibitor of Toxoplasma gondii (T. gondii) parasite entrance into the host cells. Therefore, the focus of current study is characterization of the anti-Toxoplasma activity of KET in the acute phase of toxoplasmosis in murine model as pre-treatment and post-treatment (before and after infection with RH strain). KET was used intraperitoneally both individually (2 and 3 mg/kg/day) and in combination with pyrimethamine (PYR) (50 mg/kg/day). One week after the post infection, DNA was extracted from brain biopsies samples. Parasite load was calculated using Quantitative-PCR (Q-PCR) in a triplicate reaction for each DNA with the target for at RE (a 529 bp repeat element) gene.ResultsA significant difference between KET and control groups was observed (P < 0.001) in the pre-treatment and post-treatment groups. Both KET and the combination of KET and PYR showed a reduction in the parasite load in brain through the acute phase of the infection. 2 mg/kg/day dose of KET resulted in higher anti-Toxoplasma activity (15,698 parasites/ml) compared to 3 mg/kg/day dose of KET (72,898 parasites/ml) in brain in the pre-treatment group. In addition, KET combined with PYR significantly decreased the parasite load in the post-treatment group.ConclusionsOur results indicated that KET has both prophylactic and therapeutic effects on acute phases of the disease.
Highlights
Standard treatment of toxoplasmosis is accompanied by severe side effects and low tolerability; alternative medicines are critically needed
Parasites Tachyzoites of the highly virulent RH strain of T. gondii were used for experiments which routinely obtained by serial intraperitoneal (IP) passages in Balb/c female mice in Toxoplasmosis Research Center, Mazandaran University of Medical Sciences, Sari, Iran [7, 16]
In the pre-treatment group, the highest parasitic load of T. gondii was observed in the negative control group (865,548 parasites/ml)
Summary
Standard treatment of toxoplasmosis is accompanied by severe side effects and low tolerability; alternative medicines are critically needed. Ketotifen (KET) as a cell membrane stabilizer could be an appropriate inhibitor of Toxoplasma gondii (T. gondii) parasite entrance into the host cells. The focus of current study is characterization of the anti-Toxoplasma activity of KET in the acute phase of toxoplasmosis in murine model as pre-treatment and post-treatment (before and after infection with RH strain). Parasite load was calculated using Quantitative-PCR (Q-PCR) in a triplicate reaction for each DNA with the target for at RE (a 529 bp repeat element) gene. Toxoplasma gondii (T. gondii), a ubiquitous intracellular parasite, is the etiologic agent of toxoplasmosis [1]. Over 1 billion of the world population is chronically infected by T. gondii. This infection can be transmitted to humans by various transmission pathways [2]. Acquiring the infection during pregnancy via congenital route,
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