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.

中文翻译：

---

绿色合成铜纳米粒子对小鼠弓形虫感染的高效预防

目的

目前，由于缺乏预防弓形虫病的有效疫苗，乙胺嘧啶和磺胺嘧啶联合化疗被认为是治疗弓形虫病的“金标准”。最近的报道表明，这些合成的化学药物与一些严重的副作用有关。本研究旨在评估由刺山柑果实甲醇提取物单独合成的绿色铜纳米粒子（CuNPs）与阿托伐醌联合对德黑兰弓形虫德黑兰株诱导的小鼠慢性弓形虫病的预防作用。

方法

然后以 2 和 4 mg/kg/天的剂量给小鼠口服 CuNPs，并与 atovaquone 50 mg/kg 联合给药 14 天。雄性BALB/c小鼠分为二七组，包括C1（未治疗未感染）；C2（用生理盐水处理）；C3（用 atovaquone 100 mg/kg/天处理的感染小鼠）；Ex1（用 2 mg/kg/天的 CuNPs 处理）；Ex2（用 4 mg/kg/天的 CuNPs 处理）；Ex3（用 CuNPs 2 mg/kg/天 + atovaquone 50 mg/kg/天处理）；Ex3（用 CuNPs 4 mg/kg/天 + atovaquone 50 mg/kg/天处理）。在第 15 天，小鼠腹膜内接种了来自德黑兰弓形虫菌株的 20-25 个组织囊肿。测量各测试组小鼠脑组织囊肿的平均数和IL-12、IFN-γ和诱导型一氧化氮合酶（iNOS）的mRNA水平。

结果

CuNPs 是由刺梭菌甲醇提取物绿色合成的。扫描电镜显示，CuNPs 的粒径分别为 17 和 41 nm，最大峰在 414 nm 波长处。与对照组相比，Ex1、Ex2、Ex3 和 Ex4 测试组小鼠中弓形虫组织囊肿的平均数显着降低，呈剂量依赖性反应。此外，与对照组 C3 相似，没有T. gondii在实验组Ex3和Ex4的小鼠中观察到组织囊肿。在所有测试组的小鼠中测量了 IFN-γ、IL-12 和 iNO 的 mRNA 水平。与对照组C2相比，实验组所有小鼠的IFN-γ、IL-12、iNO mRNA水平升高；然而，与对照组C3相比，在Ex3和Ex4的测试组中检测到IFN-γ、IL-12和iNO的mRNA水平显着增强。

结论

获得的结果表明，单独使用 CuNPs 并与 atovaquone 联合使用可预防小鼠弓形虫病。虽然，CuNPs 的预防作用和其他特性，如提高细胞免疫和低毒性，是积极的话题；然而，需要更多的研究来批准这些发现，尤其是在临床环境中。