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Effect of Propranolol Alone and in Combination with Pyrimethamine on Acute Murine Toxoplasmosis.

Abstract：

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. OBJECTIVES:In this study, we investigated the anti-Toxoplasma gondii efficacy of propranolol in vivo. MATERIALS AND 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.

journal_name

Jundishapur J Microbiol

journal_title

Jundishapur journal of microbiology

authors

Montazeri M,Daryani A,Ebrahimzadeh M,Ahmadpour E,Sharif M,Sarvi S

doi

10.5812/jjm.22572

subject

Has Abstract

pub_date

2015-09-07 00:00:00

pages

e22572

issue

eissn

2008-3645

issn

2008-4161

journal_volume

pub_type

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Effect of Propranolol Alone and in Combination with Pyrimethamine on Acute Murine Toxoplasmosis.