The results indicated that treatment with propranolol (2 mg/kg/day) decreased the parasite load in the brain (1,630 parasites/ml) and spleen (2,170 parasites/ml) tissues
The results indicated that treatment with propranolol (2 mg/kg/day) decreased the parasite load in the brain (1,630 parasites/ml) and spleen (2,170 parasites/ml) tissues. 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-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. INTRODUCTION Toxoplasmosis is a widespread infection caused by the obligate intracellular protozoan parasite (1). is classified by the National Institutes of Health and Centers for Disease Control (CDC) as a category B human-infectious pathogen. Over 1 billion people are estimated to be infected with globally (2). Toxoplasmosis in immunocompetent people is usually asymptomatic or appears as flulike symptoms, swollen lymph glands, muscle Nkx2-1 aches, and pain that may last from a few days to several weeks (3). In HIV-positive individuals and patients with other immunosuppressive disorders, toxoplasmosis may cause severe symptoms, such as necrotizing encephalitis, pneumonitis, chorioretinitis, and myocarditis, and death (4, 5). Furthermore, acute infection during pregnancy is a major cause of spontaneous abortion, gastrointestinal complications, intrauterine fetal death, preterm delivery, or serious fetal malformations, including encephalitis and ocular and cerebral syndromes. Recently, infections with have also been linked to possible increased risk for autism and early onset of schizophrenia (2, 5). In addition, toxoplasmosis is considered the third most common nosocomially acquired foodborne disease and can lead to death if it is not treated (2). The recommended drugs for treatment or prophylaxis of toxoplasmosis are pyrimethamine and sulfadiazine. These drugs have side effects such as neutropenia, severe drop of platelet count, thrombocytopenia, leucopenia, elevation in serum creatinine and PAP-1 (5-(4-Phenoxybutoxy)psoralen) serum liver enzymes, hematological abnormalities, and hypersensitivity reactions (6). In addition, other drugs, such as azithromycin, clarithromycin, spiramycin, atovaquone, dapsone, and co-trimoxazole (trimethoprim-sulfamethoxazole), have been used for clinical toxoplasmosis (7,C10). Spiramycin monotherapy can be effective during the early stage of pregnancy to prevent prenatal transmission. More than 50% of patients treated with spiramycin retained DNA in blood and remained infected (2). So, for prevention/eradication of the chronic infection or protection against congenital toxoplasmosis, current chemotherapy is not safe or effective. Therefore, it is necessary to investigate new and more-effective therapeutic agents with low toxicity to treat this disease (2, 7, 11). during the host cell invasion attaches to the host cell with its apical end. This mechanism often occurs as a direct result of active gliding motility. Moreover, surface antigens such as perforinlike protein aid in the interaction between the tachyzoite and the host cell. The process is accompanied by three sequentially discharged sets of morphologically and functionally distinct secretory organelles: micronemes, rhoptries, and dense granules. Invasion PAP-1 (5-(4-Phenoxybutoxy)psoralen) occurs faster than phagocytosis. Disruption of any of these essential functions would be expected PAP-1 (5-(4-Phenoxybutoxy)psoralen) to kill or inhibit the parasite (12, 13). It is known that the cell membrane-stabilizing drugs change the resistance of the cell membrane by blocking the actin gel and interfering with microfilament functions (14, 15). Previously, we have shown that ketotifen at 2 mg/kg of body weight (16), chromolyn sodium at 10 mg/kg (17), and propranolol at 2 or 3 3 mg/kg (18) used as cell membrane-stabilizing drugs inhibited penetration into nucleated cells. The aim of the present study was to determine propranolol anti-activity during the acute and chronic phases of experimental toxoplasmosis in a murine model. MATERIALS AND METHODS Parasites used in acute and chronic phases. Tachyzoites of the virulent strain RH of = 4) under standard laboratory conditions (with an average temperature of 20 to 25C) and were given drinking water and a regular mouse or rat diet (21). Experimental design and PAP-1 (5-(4-Phenoxybutoxy)psoralen) groups in acute and chronic phases. Acute-phase experiments were performed in two separate pretreatment and posttreatment groups. In each group, 24 female BALB/c mice in six subgroups (= 4) were used for the assessment of anti-effects of drugs, including propranolol at 2 mg/kg/day, propranolol at 3 mg/kg/day, pyrimethamine (50 mg/kg/day) plus propranolol.