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

Abstract

dCurrent 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 ؋ 10 3 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 1 ؋ 10 6 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.

Anti-Toxoplasma Activities of Zea Mays and Eryngium Caucasicum Extracts, In Vitro and In Vivo

“…Previously we have shown that the propranolol and ketotifen combined with pyrimethamine was more effective in inhibiting growth of tachyzoites when compared with propranolol and pyrimethamine alone on murine toxoplasmosis [35, 36, 37]. Therefore, further studies should be performed to compare the efficacy of Z. mays and E. caucasicum combination in inhibiting growth of T. gondii.…”

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“…Spiramycin and metronidazole had synergistic effect in recovery of brain cysts caused by chronic toxoplasmosis. This is due to the influence of metronidazole on increased permeability of the brain to spiramycin; thus, the combination of these two drugs is prescribed to treat cerebral cysts in patients with chronic toxoplasmosis 21,22 .…”

Anti-Toxoplasma Effects of Methanol Extracts of Feijoa sellowiana, Quercus castaneifolia, and Allium paradoxum

“…Thus, new, less toxic compounds for use against Toxoplasma are critically needed [12, 26]. Natural compounds and traditional herbal medicine have high availability and lower side effects compared with current chemical drugs [16].…”