Reactivation of Toxoplasma gondii
infections and serious clinical manifestations such as
encephalitis may develop in immunocompromised subjects and
AIDS patients. Different protocols are used for the treatment of
toxoplasmosis in high-risk patient groups, however life-long prophylactic
therapy against reactivation risk in
AIDS patients may lead to several undesired results.
Atovaquone is an effective antiprotozoal agent against
toxoplasmosis with minor side effects. On the other hand,
Astragalus membranaceus root extract (
AmE) has been shown to have immunomodulatory and antimicrobial activities, empowering immunity by enhancing proliferation and activation of phagocytic cells mainly macrophages, and inducing Th1 type immune response. The aim of this study was to investigate the effectiveness of
atovaquone alone and in combination with
AmE, in the treatment of
toxoplasmosis, and on the levels of
IL-2,
IL-12 and IFN-γ in experimentally infected mice with T.gondii. For this purpose, four experimental groups, each consisting of eight BALB/c mice, were set with the approval of Ethics Committee for the Animal Experiments. All the mice were infected with 0.5 ml of a
suspension containing 2 x 104/ml trophozoites prepared from T.gondii RH strain by
intraperitoneal injection. Twenty-four hours after the
infection,
atovaquone (100 mg/kg/day) was given to
atovaquone group,
AmE (0.075 mg/g) to astragalus group and
atovaquone (100 mg/kg/day) plus
AmE (0.075 mg/g) to
Atovaquone + Astragalus (Ato + Astra) group by oral gavage. The mice in the fourth group, which was the control group, were all infected but untreated. The above administrations were carried out for seven days. On the 8th day peritoneal fluids of mice were collected under anaesthesia and trophozoite numbers per 1 ml were detected by counting on the Thoma slide. In addition, the heart bloods of mice were drawn and
IL-2,
IL-12, IFN-γ levels were determined in serum samples by using commercial ELISA kits (eBioscience, Austria). The mean number of trophozoites in Ato + Astra group was found significantly lower than the number of trophozoites in the other three groups (p< 0.05). The number of trophozoites in the
atovaquone and astragalus groups were found significantly lower than the number of trophozoites in the control group (p< 0.05). There was a significant increase in
IL-2 levels of astragalus group compared with the other three groups, in addition when
IL-2 levels of Ato + Astra group were compared with ones in other three groups, a significant decrease was noticed (p< 0.05). There was a definite increase in
IL-12 levels of
atovaquone, astragalus and the control groups compared to those in Ato + Astra group (p< 0.05). A significant increase was found in IFN-γ levels in
atovaquone and Ato + Astra groups compared with those in the control group (p< 0.05). Within the reach of our literature survey, this study was the first research in which the effectiveness of the combination of
atovaquone and
AmE was investigated in the treatment of acute
toxoplasmosis. The results of our study suggested that there might be a synergy between
atovaquone and
AmE in the treatment of acute
toxoplasmosis. In case these results are supported by further studies,
atovaquone and
AmE combination may have a potential to be used for
therapy in immunocompromized patients such as
AIDS patients who have a risk for
toxoplasmosis.