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齐多夫定(AZT)处理后美洲钩端螺旋体(L.)亚马逊滋养体的形态改变和生长抑制。

Morphological alterations and growth inhibition of Leishmania (L.)amazonensis promastigotes exposed to zidovudine (AZT).

机构信息

Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Setor Universitário, Goiania, GO, Brazil.

出版信息

Parasitol Res. 2011 Mar;108(3):547-51. doi: 10.1007/s00436-010-2096-3. Epub 2010 Oct 5.


DOI:10.1007/s00436-010-2096-3
PMID:20922414
Abstract

Leishmania parasites cause a worldwide public health disease and its treatment is still based on pentavalent antimonials which present financial and toxicologic limitations. Some nucleosidic derivatives have demonstrated anti-leishmanial properties and this study aims to evaluate the in vitro morphologic alterations and growth inhibition of Leishmania (L.) amazonensis promastigotes exposed to zidovudine at several concentrations. The citotoxicity of zidovudine (AZT) to macrophages was determined by an MTT assay. After which the promastigotes were exposed to concentrations of AZT, ranging from 1 to 50 μM. The evaluation of survival and morphometry alterations were performed in two distinct phases of in vitro growth, on the third and sixth days, representing the logarithmic and stationary phases, respectively. Slides with the promastigotes were photographed and analyzed using Image J. A significant reduction of parasite number in the logarithmic phase of in vitro growth was observed when the parasites were submitted to 20, 30, 40, and 50 μM of AZT. Morphometric alterations were observed such as an increase in width of the body, cytoplasmic granulations and vacuolizations. These data indicate the toxicity of AZT which prevents the parasite's multiplication, indicating a promising use of AZT as an anti-leishmania drug.

摘要

利什曼原虫寄生虫引起全球公共卫生疾病,其治疗仍基于五价锑,存在经济和毒理学限制。一些核苷衍生物已被证明具有抗利什曼原虫的特性,本研究旨在评估齐多夫定(AZT)在不同浓度下对利什曼原虫(L.)亚马逊株前鞭毛体的体外形态改变和生长抑制作用。通过 MTT 测定法确定 AZT 对巨噬细胞的细胞毒性。然后将前鞭毛体暴露于 1 至 50 μM 的 AZT 浓度下。在体外生长的对数和静止阶段,分别在第 3 天和第 6 天进行生存和形态计量改变的评估。用 AZT 处理后,用载玻片拍摄并使用 Image J 分析前鞭毛体。当寄生虫处于对数生长期时,暴露于 20、30、40 和 50 μM 的 AZT 时,寄生虫数量明显减少。观察到形态计量改变,如体宽增加、细胞质颗粒和空泡化。这些数据表明 AZT 的毒性可防止寄生虫繁殖,表明 AZT 有望用作抗利什曼原虫药物。

相似文献

[1]
Morphological alterations and growth inhibition of Leishmania (L.)amazonensis promastigotes exposed to zidovudine (AZT).

Parasitol Res. 2010-10-5

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[1]
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Sci Rep. 2024-9-28

[2]
Immunomodulatory Therapy of Visceral Leishmaniasis in Human Immunodeficiency Virus-Coinfected Patients.

Front Immunol. 2018-1-12

[3]
Antileishmanial activity of antiretroviral drugs combined with miltefosine.

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[4]
Structural and Kinetic Characterization of Thymidine Kinase from Leishmania major.

PLoS Negl Trop Dis. 2015-5-15

本文引用的文献

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Bioorg Chem. 2005-12

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