Effect of Propranolol Alone and in Combination with Pyrimethamine on Acute Murine Toxoplasmosis.
BACKGROUND
Toxoplasmosis is a public health problem worldwide. This complication principally affects immunodeficient patients and pregnant women. Toxoplasma gondii is an opportunistic parasite, causing severe illness among and death of high-risk individuals and treatment is becoming increasingly difficult owing to side effects and low efficacies of drugs.


OBJECTIVE
In this study, we investigated the anti-Toxoplasma gondii efficacy of propranolol in vivo.


METHODS
This study was performed in two separate pre-treatment and post-treatment groups. In each group, 18 female Balb/c mice in six subgroups (n = 3) were used to assess the anti-Toxoplasma effect of propranolol at 2 and 3 mg/kg/day, pyrimethamine at 50 mg/kg/day, propranolol at 2 and 3 mg/kg/day plus pyrimethamine, and phosphate-buffered saline (PBS; as negative control). Treatment was performed 4, 24, and 48 hours before and after an intraperitoneal challenge of 1 × 10(3) tachyzoites of the virulent RH strain of T. gondii, in pre-treatment and post-treatment groups. Mice peritoneal exudates were collected on the seventh day after the challenge and parasite numbers were recorded as percent of growth inhibition and survival rate.


RESULTS
In the pre-treatment group, results showed that propranolol at 2 and 3 mg/kg combined with pyrimethamine was more effective in inhibiting growth of tachyzoites (86% and 98%, respectively) when compared with propranolol at 2 and 3 mg/kg (37% and 39%, respectively) and pyrimethamine (41%) alone. In the post-treatment group, all combined treatments significantly reduced parasite load. The growth inhibition of tachyzoites in mice receiving propranolol (2 and 3 mg/kg) was 75% and 51%, with the mean tachyzoites count being 1526 ± 171.4 and 2948 ± 1452.8, respectively, compared with pyrimethamine treatment outcome, which represents 99.9% growth inhibition.


CONCLUSIONS
Our results demonstrated the promising prophylactic and therapeutic effects of propranolol against T. gondii infection. Propranolol also increases the efficacy of pyrimethamine in combination therapies.
Toxoplasmosis Research Center, Mazandaran University of Medical Sciences, Sari, IR Iran ; Department of Parasitology and Mycology, Sari Medical School, Mazandaran University of Medical Sciences, Sari, IR Iran.
Mahbobeh
M
Montazeri
Toxoplasmosis Research Center, Mazandaran University of Medical Sciences, Sari, IR Iran ; Department of Parasitology and Mycology, Sari Medical School, Mazandaran University of Medical Sciences, Sari, IR Iran.
Ahmad
A
Daryani
Pharmaceutical Sciences Research Center, School of Pharmacy, Mazandaran University of Medical Sciences Sari, IR Iran.
Mohammadali
M
Ebrahimzadeh
Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, IR Iran.
Ehsan
E
Ahmadpour
Toxoplasmosis Research Center, Mazandaran University of Medical Sciences, Sari, IR Iran ; Department of Parasitology and Mycology, Sari Medical School, Mazandaran University of Medical Sciences, Sari, IR Iran.
Mehdi
M
Sharif
Toxoplasmosis Research Center, Mazandaran University of Medical Sciences, Sari, IR Iran ; Department of Parasitology and Mycology, Sari Medical School, Mazandaran University of Medical Sciences, Sari, IR Iran.
Shahabeddin
S
Sarvi
Mice; Propranolol; Pyrimethamine; Toxoplasma