Survey on synergism effect of ketotifen in combination with pyrimethamine in treatment of acute murine toxoplasmosis

Abstract

Background

Standard 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.

Results

A 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.

Conclusions

Our results indicated that KET has both prophylactic and therapeutic effects on acute phases of the disease.