| Current therapies against toxoplasmosis are limited, and drugs have significant side effects and low efficacies. We evaluated the
potential anti-Toxoplasma activity of propranolol at a dose of 2 or 3 mg/kg of body weight/day in vivo in the acute and chronic
phases. Propranolol as a cell membrane-stabilizing agent is a suitable drug for inhibiting the entrance of Toxoplasma gondii
tachyzoites into cells. The acute-phase assay was performed using propranolol, pyrimethamine, and propranolol plus pyrimethamine
before (pretreatment) and after (posttreatment) intraperitoneal challenge with 1 103 tachyzoites of the virulent T. gondii
strain RH in BALB/c mice. Also, in the chronic phase, treatment was performed 12 h before intraperitoneal challenge with
1106 tachyzoites of the virulent strain RH of T. gondii in 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-Toxoplasma activity was observed using propranolol (P<
0.001). Propranolol in the pretreatment group showed higher anti-Toxoplasma activity 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-Toxoplasma
activity 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. |