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C 富勒烯调控阿霉素对体外大鼠小胶质细胞代谢谱的影响。

C Fullerene Governs Doxorubicin Effect on Metabolic Profile of Rat Microglial Cells In Vitro.

机构信息

Bogomolets National Medical University, 13, T. Shevchenko blvd, 01601 Kyiv, Ukraine.

Taras Shevchenko National University of Kyiv, Volodymyrska str., 64, 01601 Kyiv, Ukraine.

出版信息

Mol Pharm. 2020 Sep 8;17(9):3622-3632. doi: 10.1021/acs.molpharmaceut.0c00691. Epub 2020 Jul 28.

DOI:10.1021/acs.molpharmaceut.0c00691
PMID:32673486
Abstract

: C fullerenes and their derivatives are actively investigated for the use in neuroscience. Applications of these nanoscale materials require the examination of their interaction with different neural cells, especially with microglia, because these cells, like other tissue resident phagocytes, are the earliest and most sensitive responders to nanoparticles. The of this study was to investigate the effect of C fullerene and its nanocomplex with doxorubicin (Dox) on the metabolic profile of brain-resident phagocytes-microglia-in vitro. : Resting microglial cells from adult male Wistar rats were used in experiments. Potential C fullerene targets in microglial cells were studied by computer simulation. Microglia oxidative metabolism and phagocytic activity were examined by flow cytometry. Griess reaction and arginase activity colorimetric assay were used to explore arginine metabolism. : C fullerene when used alone did not influence microglia oxidative metabolism and phagocytic activity but shifted arginine metabolism toward the decrease of NO generation. Complexation of C fullerene with Dox (C-Dox) potentiated the ability of the latter to stimulate NO generation. : The capability of C fullerenes used alone to cause anti-inflammatory shift of microglia arginine metabolism makes them a promising agent for the correction of neuroinflammatory processes involved in neurodegeneration. The potentiating action of C fullerene on the immunomodulatory effect of Dox allows us to consider the C molecule as an attractive vehicle for this antitumor agent.

摘要

富勒烯及其衍生物在神经科学领域的应用研究十分活跃。这些纳米材料的应用需要研究它们与不同神经细胞的相互作用,特别是与小胶质细胞的相互作用,因为这些细胞与其他组织驻留吞噬细胞一样,是对纳米颗粒最早和最敏感的反应者。本研究的目的是研究富勒烯及其与阿霉素(Dox)的纳米复合物对体外脑驻留吞噬细胞-小胶质细胞代谢谱的影响。

在实验中使用了来自成年雄性 Wistar 大鼠的静止小胶质细胞。通过计算机模拟研究了富勒烯在小胶质细胞中的潜在靶标。通过流式细胞术研究了小胶质细胞的氧化代谢和吞噬活性。使用格里斯反应和精氨酸酶活性比色法研究精氨酸代谢。

单独使用富勒烯不会影响小胶质细胞的氧化代谢和吞噬活性,但会使精氨酸代谢向减少 NO 生成的方向转移。富勒烯与阿霉素(C-Dox)的复合物增强了后者刺激 NO 生成的能力。

富勒烯单独使用引起小胶质细胞精氨酸代谢抗炎转移的能力使其成为纠正与神经退行性变相关的神经炎症过程的有前途的药物。富勒烯对阿霉素免疫调节作用的增强作用使我们将 C 分子视为这种抗肿瘤药物的有吸引力的载体。

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C Fullerene Governs Doxorubicin Effect on Metabolic Profile of Rat Microglial Cells In Vitro.C 富勒烯调控阿霉素对体外大鼠小胶质细胞代谢谱的影响。
Mol Pharm. 2020 Sep 8;17(9):3622-3632. doi: 10.1021/acs.molpharmaceut.0c00691. Epub 2020 Jul 28.
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