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亚硝化应激诱导肠贾第虫细胞毒性。

Nitrosative stress induced cytotoxicity in Giardia intestinalis.

作者信息

Lloyd D, Harris J C, Maroulis S, Mitchell A, Hughes M N, Wadley R B, Edwards M R

机构信息

Department of Microbiology, Cardiff University, Cardiff, Wales, UK.

出版信息

J Appl Microbiol. 2003;95(3):576-83. doi: 10.1046/j.1365-2672.2003.02008.x.

DOI:10.1046/j.1365-2672.2003.02008.x
PMID:12911706
Abstract

AIMS

To investigate the antigiardial properties of the nitrosating agents: sodium nitrite, sodium nitroprusside and Roussin's black salt.

METHODS AND RESULTS

Use of confocal laser scanning microscopy and flow cytometry indicated permeabilization of the plasma membrane to the anionic fluorophore, DiBAC4(3) [bis(1,3-dibutylbarbituric acid) trimethine oxonol]. Loss of plasma membrane electrochemical potential was accompanied by loss of regulated cellular volume control. Changes in ultrastructure revealed by electron microscopy and capacity for oxygen consumption, were also consequences of nitrosative stress. Roussin's black salt (RBS), active at micromolar concentrations was the most potent of the three agents tested.

CONCLUSIONS

These multitargeted cytotoxic agents affected plasma membrane functions, inhibited cellular functions in Giardia intestinalis and led to loss of viability.

SIGNIFICANCE AND IMPACT OF THE STUDY

Nitrosative damage, as an antigiardial strategy, may have implications for development of chemotherapy along with suggesting natural host defence mechanisms.

摘要

目的

研究亚硝化剂亚硝酸钠、硝普钠和鲁辛黑盐的抗贾第虫特性。

方法与结果

共聚焦激光扫描显微镜和流式细胞术的使用表明,质膜对阴离子荧光团二丁基巴比妥酸三甲川羰花青(DiBAC4(3))发生了通透化。质膜电化学电位的丧失伴随着调节性细胞体积控制的丧失。电子显微镜显示的超微结构变化以及氧消耗能力也是亚硝化应激的结果。鲁辛黑盐(RBS)在微摩尔浓度下具有活性,是所测试的三种试剂中最有效的。

结论

这些多靶点细胞毒性剂影响质膜功能,抑制肠贾第虫的细胞功能并导致活力丧失。

研究的意义和影响

亚硝化损伤作为一种抗贾第虫策略,可能对化疗的发展有影响,同时也提示了天然宿主防御机制。

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