Evaluation of Propranolol Effect on Experimental Acute and Chronic Toxoplasmosis Using Quantitative PCR

ABSTRACTCurrent therapies against toxoplasmosis are limited, and drugs have significant side effects and low efficacies. We evaluated the potential anti-Toxoplasmaactivity of propranolol at a dose of 2 or 3 mg/kg of body weight/day in vivoin the acute and chronic phases. Propranolol as a cell membrane-stabilizing agent is a suitable drug for inhibiting the entrance of Toxoplasma gondiitachyzoites into cells. The acute-phase assay was performed using propranolol, pyrimethamine, and propranolol plus pyrimethamine before (pretreatment) and after (posttreatment) intraperitoneal challenge with 1 × 103tachyzoites of the virulent T. gondiistrain RH in BALB/c mice. Also, in the chronic phase, treatment was performed 12 h before intraperitoneal challenge with 1 × 106tachyzoites of the virulent strain RH of T. gondiiin rats. One week (in the acute phase) and 2 months (in the chronic phase) after postinfection, tissues were isolated and DNA was extracted. Subsequently, parasite load was calculated using quantitative PCR (qPCR). In the acute phase, in both groups, significant anti-Toxoplasmaactivity was observed using propranolol (P< 0.001). Propranolol in the pretreatment group showed higher anti-Toxoplasmaactivity than propranolol in posttreatment in brain tissues, displaying therapeutic efficiency on toxoplasmosis. Also, propranolol combined with pyrimethamine reduced the parasite load as well as significantly increased survival of mice in the pretreatment group. In the chronic phase, anti-Toxoplasmaactivity and decreased parasite load in tissues were observed with propranolol. In conclusion, the presented results demonstrate that propranolol, as an orally available drug, is effective at low doses against acute and latent murine toxoplasmosis, and the efficiency of the drug is increased when it is used in combination therapy with pyrimethamine.