title: Evaluation of Propranolol Effect on Experimental Acute and Chronic Toxoplasmosis Using Quantitative PCR.
abstract: 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 × 103tachyzoites 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 1 × 106tachyzoites 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.
authors.affiliation: Toxoplasmosis Research Center, Mazandaran University of Medical Sciences, Sari, Iran.|Department of Parasitology and Mycology, Sari Medical School, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Mahbobeh
authors.initials: M
authors.lastname: Montazeri
authors.affiliation: Pharmaceutical Sciences Research Center, School of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Ebrahimzadeh
authors.affiliation: Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Ehsan
authors.initials: E
authors.lastname: Ahmadpour
authors.affiliation: Toxoplasmosis Research Center, Mazandaran University of Medical Sciences, Sari, Iran.|Department of Parasitology and Mycology, Sari Medical School, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Sharif
authors.affiliation: Toxoplasmosis Research Center, Mazandaran University of Medical Sciences, Sari, Iran.|Department of Parasitology and Mycology, Sari Medical School, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Shahabeddin
authors.initials: S
authors.lastname: Sarvi
authors.affiliation: Toxoplasmosis Research Center, Mazandaran University of Medical Sciences, Sari, Iran daryanii@yahoo.com.|Department of Parasitology and Mycology, Sari Medical School, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Daryani
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D005260:Female; D008807:Mice, Inbred BALB C; D059208:Parasite Load; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D015996:Survival Rate; D014122:Toxoplasma / Q000235:genetics / Q000472:pathogenicity; D014124:Toxoplasmosis, Animal / Q000188:drug therapy* / Q000401:mortality
chemical_list: D000981:Antiprotozoal Agents; D011433:Propranolol