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绿色合成铜纳米颗粒对预防小鼠弓形虫感染的高效性

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

作者信息

Albalawi Aishah E, Alanazi Abdullah D, Alyousif Mohamed S, Sepahvand Azadeh, Ebrahimi Katrin, Niazi Massumeh, Mahmoudvand Hossein

机构信息

Department of Biology, Faculty of Science, University of Tabuk, Tabuk, Saudi Arabia.

Faculty of Science and Humanities, Department of Biological Sciences, Shaqra University, P.O. Box 1040, Ad-Dawadimi, 11911, Saudi Arabia.

出版信息

Acta Parasitol. 2021 Dec;66(4):1472-1479. doi: 10.1007/s11686-021-00421-4. Epub 2021 May 29.

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.

摘要

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弓形虫病的“金标准”治疗方法。最近的报告显示,这些合成化学药物存在一些严重的副作用。本研究旨在评估由刺山柑果实甲醇提取物单独绿色合成的铜纳米颗粒(CuNPs)以及与阿托伐醌联合使用对小鼠由刚地弓形虫德黑兰株诱导的慢性弓形虫病的预防效果。方法:然后以2和4毫克/千克/天的剂量给小鼠口服CuNPs,并与50毫克/千克的阿托伐醌联合使用,持续14天。雄性BALB/c小鼠分为两个七组,包括C1(未治疗未感染);C2(用生理盐水治疗);C3(感染小鼠用100毫克/千克/天的阿托伐醌治疗);Ex1(用2毫克/千克/天的CuNPs治疗);Ex2(用4毫克/千克/天的CuNPs治疗);Ex3(用2毫克/千克/天的CuNPs + 50毫克/千克的阿托伐醌治疗);Ex4(用4毫克/千克/天的CuNPs + 50毫克/千克的阿托伐醌治疗)。在第15天,通过腹腔接种20 - 25个来自刚地弓形虫德黑兰株的组织包囊使小鼠感染。测量每个测试组小鼠脑组织包囊的平均数以及IL - 12、IFN - γ和诱导型一氧化氮合酶(iNOS)的mRNA水平。

结果

CuNPs由刺山柑甲醇提取物绿色合成。扫描电子显微镜显示CuNPs的粒径为17和41纳米,在波长414纳米处有最大峰值。与对照组相比,Ex1、Ex2、Ex3和Ex4测试组小鼠中弓形虫组织包囊的平均数呈剂量依赖性显著下降。此外,与对照组C3类似,在实验组Ex3和Ex4的小鼠中未观察到弓形虫组织包囊。测量了所有测试组小鼠中IFN - γ、IL - 12和iNO的mRNA水平。与对照组C2相比,所有实验组小鼠中IFN - γ、IL - 12和iNO的mRNA水平均升高;然而,与对照组C3相比,在Ex3和Ex4测试组中IFN - γ、IL - 12和iNO的mRNA水平有显著提高。

结论

获得的结果显示CuNPs单独以及与阿托伐醌联合使用对预防小鼠弓形虫病具有高效力。尽管CuNPs的预防效果以及其他特性,如改善细胞免疫和低毒性,是积极的课题;然而,需要更多研究来证实这些发现,尤其是在临床环境中。

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