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生物成因硒纳米颗粒对利什曼原虫的疗效:体外和体内研究。

Efficacy of biogenic selenium nanoparticles against Leishmania major: in vitro and in vivo studies.

机构信息

Department of Parasitology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran 14117, Iran.

出版信息

J Trace Elem Med Biol. 2013 Jul;27(3):203-7. doi: 10.1016/j.jtemb.2012.11.002. Epub 2012 Dec 6.

Abstract

PROJECT

This study investigated the in vitro and in vivo effectiveness of biogenic selenium nanoparticles (Se NPs), biosynthesized by Bacillus sp. MSh-1, against Leishmania major (MRHO/IR/75/ER).

PROCEDURE

The 3-(4,5-dimethylthiozol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was used to evaluate the cytotoxicity effects of the biogenic Se NPs against both promastigote and amastigote forms of L. major. In a separate in vivo experiment, we also determined the preventive and therapeutic effects of biogenic Se NPs in BALB/c mice following subcutaneous infected with L. major.

RESULTS

The MTT assays showed that the highest toxicity occurred after 72 h against both promastigote and amastigote forms of L. major. The cytotoxicity of Se NPs was higher at all incubation times (24, 48, and 72 h) against the promastigote than the amastigote form (p<0.05). The 50% inhibitory concentrations (IC50) of the Se NPs were 1.62±0.6 and 4.4±0.6 μg ml(-1) against the promastigote and amastigote forms, respectively, after a 72-h incubation period. Apoptosis assays showed DNA fragmentation in promastigotes treated with Se NPs. In an animal challenge, prophylactic doses of biogenic Se NPs delayed the development of localized cutaneous lesions. Moreover, daily administration of Se NPs (5 or 10 mg kg(-1) day(-1)) in similarly infected BALB/c mice that had not received prophylactic doses of Se NPs also abolished the localized lesions after 14 days.

CONCLUSION

Based on these in vitro and in vivo studies, biogenic Se NPs can be considered as a novel therapeutic agent for treatment of the localized lesions typical of cutaneous leishmaniasis.

摘要

项目

本研究调查了由芽孢杆菌 MSh-1 生物合成的生物硒纳米粒子(Se NPs)对利什曼原虫(MRHO/IR/75/ER)的体外和体内有效性。

程序

使用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)测定法评估生物合成的 Se NPs 对利什曼原虫的前鞭毛体和无鞭毛体形式的细胞毒性作用。在单独的体内实验中,我们还确定了在 BALB/c 小鼠皮下感染利什曼原虫后,生物合成的 Se NPs 的预防和治疗效果。

结果

MTT 测定法显示,在前鞭毛体和无鞭毛体形式的利什曼原虫中,72 小时后毒性最高。Se NPs 的细胞毒性在前鞭毛体形式中所有孵育时间(24、48 和 72 小时)均高于无鞭毛体形式(p<0.05)。Se NPs 的 50%抑制浓度(IC50)分别为 1.62±0.6 和 4.4±0.6 μg ml(-1),在 72 小时孵育后针对前鞭毛体和无鞭毛体形式。凋亡测定显示,用 Se NPs 处理的前鞭毛体中有 DNA 片段化。在动物挑战中,生物合成的 Se NPs 的预防性剂量延迟了局部皮肤损伤的发展。此外,在未接受预防性剂量 Se NPs 的类似感染的 BALB/c 小鼠中每天给予 5 或 10 mg kg(-1) day(-1) 的 Se NPs 也在 14 天后消除了局部病变。

结论

基于这些体外和体内研究,生物合成的 Se NPs 可被视为治疗皮肤利什曼病典型局部病变的新型治疗剂。

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