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金诺芬对克氏锥虫、热带利什曼原虫和刚地弓形虫的抗原生动物活性:体外和体内研究。

Antiprotozoal activity of auranofin on Trypanosoma cruzi, Leishmania tropica and Toxoplasma gondii: in vitro and ex vivo study.

机构信息

Manisa Celal Bayar University, Medical Faculty, Department of Parasitology, Uncubozköy, 45030 Manisa, Turkey.

出版信息

Trans R Soc Trop Med Hyg. 2023 Oct 3;117(10):733-740. doi: 10.1093/trstmh/trad040.

Abstract

BACKGROUND

Three obligate intracellular protozoan parasite species, which are responsible for significant morbidity and mortality and settle in macrophage cells, affect more than one-half of the world's population, namely, Trypanosoma cruzi, Leishmania tropica and Toxoplasma gondii, which are causative agents of Chagas disease, leishmaniasis and toxoplasmosis, respectively. In the current study, it was aimed to investigate the in vitro and ex vivo antiprotozoal activity of auranofin on T. cruzi, L. tropica and T. gondii.

METHODS

The in vitro drug efficacy (IC50) of auranofin was investigated by haemocytometry and the CellTiter-Glo assay methods and the ex vivo drug efficacy (IC50) by light microscopic examination of Giemsa-stained slides. Also, the cytotoxic activity (CC50) of auranofin was examined by the CellTiter-Glo assay. The selectivity index (SI) was calculated for auranofin.

RESULTS

According to IC50, CC50 and SI data, auranofin did not exhibit cytotoxic activity on Vero cells, but exhibited antiprotozoal activity on epimastigotes and intracellular amastigotes of T. cruzi, promastigotes and intracellular amastigotes of L. tropica and intracellular tachyzoites of T. gondii (p<0.05).

CONCLUSIONS

The detection antiprotozoal activity of auranofin on T. cruzi, L. tropica and T. gondii according to the IC50, CC50 and SI values is considered an important and promising development. This is significant because auranofin may be an effective alternative treatment for Chagas disease, leishmaniasis and toxoplasmosis in the future.

摘要

背景

三种专性细胞内原生动物寄生虫,分别引起克氏锥虫病、利什曼病和弓形体病,对全球超过一半的人口造成严重的发病率和死亡率,并定殖于巨噬细胞中,这三种寄生虫分别是克氏锥虫、热带利什曼原虫和刚地弓形虫。本研究旨在探讨金诺芬对克氏锥虫、热带利什曼原虫和刚地弓形虫的体外和体内抗原生动物活性。

方法

通过血球计数器和细胞活力检测试剂盒(CellTiter-Glo)检测金诺芬的体外药物疗效(IC50),通过吉姆萨染色载玻片的光学显微镜检查检测体内药物疗效(IC50)。同时,通过细胞活力检测试剂盒(CellTiter-Glo)检测金诺芬的细胞毒性(CC50)。计算金诺芬的选择性指数(SI)。

结果

根据 IC50、CC50 和 SI 数据,金诺芬对 Vero 细胞没有细胞毒性,但对克氏锥虫的滋养体和内阿米巴体、热带利什曼原虫的前鞭毛体和内阿米巴体以及刚地弓形虫的速殖子具有抗原生动物活性(p<0.05)。

结论

根据 IC50、CC50 和 SI 值检测金诺芬对克氏锥虫、热带利什曼原虫和刚地弓形虫的抗原生动物活性被认为是一个重要且有前途的发展。这是有意义的,因为金诺芬将来可能成为治疗克氏锥虫病、利什曼病和弓形体病的有效替代药物。

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