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Common medicines for the treatment of toxoplasmosis have limited efficacy and unwanted side effects. Opiates can effect both innate and cell-mediated immunity and stimulate the immune responses in different parasitic infections. In this work, preventive and therapeutic effects of morphine were evaluated on the tachyzoites of Toxoplasma gondii and infected macrophages in vitro and in a murine model. Different concentrations of morphine (0.1 and 0.01 μg/ml) were evaluated on mortality rate of T. gondii by direct counting after 3 and 24 hours. The cytotoxic and apoptotic effects of these drugs were measured by the MTT assays and flow cytometry analysis, respectively. The same procedures were assessed in T. gondii-infected macrophages. The parasite loads were determined using quantitative polymerase chain reaction (qPCR). For in vivo assessment, BALB/c mice treated with morphine before or after infection with tachyzoites. The survival rate of animals, parasite load in the spleen, and the IFN-γ and IL-4 cytokines levels were measured. Morphine was effective on tachyzoites of T. gondii and had a reverse relationship with its concentration. The results of flow cytometry showed that the toxic effects of morphine on tachyzoites after 3 hours was not statistically significant (p<0.05). Also, apoptosis in infected MQs rose with a decreasing concentration of morphine. The parasitic load in MQs treated with morphine before infection was lower than that in cells treated after infection and the differences were statistically significant (p<0.01). In mice that received morphine before infection, survival rate, parasite load and the IFN-γ level were significantly lower than in mice treated after infection (p<0.01). The results of this study have shown that morphine in the pre-treatment group had higher anti-Toxoplasma activity than morphine in post-treatment in vitro and in murine model.
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