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金诺芬对婴儿利什曼原虫的体外和体内抗利什曼活性研究

Investigation of In Vitro and In Vivo Anti-leishmanial Activity of Auranofin on Leishmania Infantum.

作者信息

Sadeghi Hadi, Delavari Mahdi, Arbabi Mohsen, Taheri Maryam Akhavan, Rasti Sima, Hooshyar Hossein

机构信息

Department of Medical Parasitology and Mycology, Kashan University of Medical Sciences, Kashan, Iran.

Infectious Diseases Research Center, Kashan University of Medical Sciences, Kashan, Iran.

出版信息

Acta Parasitol. 2025 Sep 12;70(5):196. doi: 10.1007/s11686-025-01129-5.

Abstract

PURPOSE

Visceral leishmaniasis (VL) is a serious health-threatening disease. Existing drugs are often toxic. So alternative treatments are constantly being considered and evaluated. This study aims to investigate Auranifin as potential new antileishmanial agent.

METHODS

The fatality rate of different concentrations of auranofin (2, 4, 6, 8, 10, 12 μg/ml) on promastigote and amastigote forms after 24 h was calculated. The induction apoptosis in promastigotes by auranofin was also analyzed. Then, Leishmania-infected mice were treated with a concentration of 6.25 mg/kg and 12.5 mg/kg of Auranofin. After 1 month, the liver and spleen of the euthanized mice were separated, smears were prepared and pathology slides were prepared from the spleen and liver. Blood cell counts and liver and kidney enzymes were analyzed using heart blood. Histopathological examinations were performed on liver and spleen after treatment.

RESULTS

The fatality rate of auranofin at a concentration of 12 µg/ml on promastigote and amastigote forms of Leishmania infantum 24 h after culture was 99.35% and 94.05%, respectively. Over 90% of promastigotes and amastigotes were killed at concentrations of 8 µg/ml and 12 µg/ml of auranofin, respectively. Flow cytometry showed a high apoptosis rate (93.73%) at a concentration of 12 μg/ml. In the control group (without auranofin) 99% of cells were alive. Histopathological examination of the spleen and liver tissues showed a decrease in the degree of granulomatous and inflammatory changes in the groups treated with auranofin. Blood factors as well as Liver and kidney enzymes showed changes in both the test and control groups.

CONCLUSION

Auranofin has anti-leishmanial properties in both promastigotes and amastigotes, further studies are neecessary to explore this aspect.

摘要

目的

内脏利什曼病(VL)是一种严重威胁健康的疾病。现有药物往往有毒性。因此,替代治疗方法一直在被考虑和评估。本研究旨在调查金诺芬作为潜在的新型抗利什曼原虫药物。

方法

计算不同浓度(2、4、6、8、10、12μg/ml)的金诺芬在24小时后对前鞭毛体和无鞭毛体形式的致死率。还分析了金诺芬对前鞭毛体凋亡的诱导作用。然后,用浓度为6.25mg/kg和12.5mg/kg的金诺芬治疗感染利什曼原虫的小鼠。1个月后,分离处死小鼠的肝脏和脾脏,制备涂片,并从脾脏和肝脏制备病理切片。使用心脏血液分析血细胞计数以及肝酶和肾酶。治疗后对肝脏和脾脏进行组织病理学检查。

结果

培养24小时后,浓度为12μg/ml的金诺芬对婴儿利什曼原虫前鞭毛体和无鞭毛体形式的致死率分别为99.35%和94.05%。金诺芬浓度为8μg/ml和12μg/ml时,分别有超过90%的前鞭毛体和无鞭毛体被杀死。流式细胞术显示浓度为12μg/ml时凋亡率很高(93.73%)。在对照组(无金诺芬)中,99%的细胞存活。脾脏和肝脏组织的组织病理学检查显示,金诺芬治疗组的肉芽肿和炎症变化程度降低。血液因子以及肝酶和肾酶在试验组和对照组中均有变化。

结论

金诺芬对前鞭毛体和无鞭毛体均具有抗利什曼原虫特性,需要进一步研究来探索这一方面。

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