The High Potency of Green Synthesized Copper Nanoparticles to Prevent the Toxoplasma gondii Infection in Mice

Abstract

Purpose: Nowadays, due to the lack of an effective vaccine to prevent the toxoplasmosis, chemotherapy with the combination of pyrimethamine and sulfadiazine is considered as the "gold standard" treatment for toxoplasmosis. Recent reports have exhibited that these synthesized chemical drugs are associated with some serious side effects. The present study aims to evaluate the prophylactic effects of copper nanoparticles (CuNPs) green synthesized by Capparis spinosa fruit methanolic extract alone and combined with atovaquone against chronic toxoplasmosis induced by the Tehran strain of Toxoplasma gondii in mice METHODS: Mice were then orally administrated with CuNPs at the doses of 2 and 4 mg/kg/day and in combined with atovaquone 50 mg/kg for 14 days. Male BALB/c mice were divided into two seven groups include C1 (non-treated non-infected); C2 (treated with normal saline); C3 (Infected mice treated with atovaquone 100 mg/kg/day); Ex1 (treated with CuNPs 2 mg/kg/day); Ex2 (treated with CuNPs 4 mg/kg/day); Ex3 (treated with CuNPs 2 mg/kg/day + atovaquone 50 mg/kg/day); Ex3 (treated with CuNPs 4 mg/kg/day + atovaquone 50 mg/kg/day). On the 15th day, the mice were infected with the intraperitoneal inoculation of 20-25 tissue cysts from the Tehran strain of T. gondii. The mean numbers of brain tissue cysts and the mRNA levels of IL-12, IFN-γ, and inducible nitric oxide synthase (iNOS) in mice of each tested group were measured.

Results: CuNPs were green synthesized by C. spinosa methanolic extract. Scanning electron microscopy showed that the particle size of CuNPs was 17 and 41 nm with maximum peak at the wavelength of 414 nm. The mean number of T. gondii tissue cysts in mice of tested groups of Ex1, Ex2, Ex3, and Ex4, significantly decreased as a dose-dependent response compared with control group. Moreover, in similar to the control group C3, no T. gondii tissue cysts was observed in mice of experimental group Ex3 and Ex4. The mRNA levels of IFN-γ, IL-12, and iNO was measured in mice of all tested groups. The mRNA levels of IFN-γ, IL-12, and iNO was increased in all mice of experimental groups in comparison with the control group C2; however, a significant enhancement was detected in mRNA level of IFN-γ, IL-12, and iNO in the tested groups of Ex3 and Ex4 when compared with control group C3.

Conclusion: The obtained results revealed the high potency of CuNPs alone and combined with atovaquone to prevent toxoplasmosis in mice. Although, the prophylactic effects of CuNPs and other properties, such as improved cellular immunity and low toxicity, are positive topics; however, more studies are required to approve these findings especially in clinical settings.

Keywords: Chronic toxoplasmosis; In vivo; Mice; Nanomedicine; Toxoplasma gondii; mRNA.