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C60 fullerene governs doxorubicin effect on metabolic profile of rat microglial cells in vitro.

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Background. C60 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… Click to show full abstract

Background. C60 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, since these cells, like other tissue resident phagocytes, are earliest and most sensitive responders to nanoparticles. The aim of this study was to investigate the effect of C60 fullerene and its nanocomplex with doxorubicin (Dox) on metabolic profile of brain resident phagocytes - microglia - in vitro. Methods. Resting microglial cells from adult male Wistar rats were used in experiments. Potential C60 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. Results. C60 fullerene used alone didn't influence microglia oxidative metabolism and phagocytic activity, and shifted arginine metabolism towards the decrease of NO-generation. Complexation of C60 fullerene with Dox (C60-Dox) potentiated the ability of the latter to stimulate NO generation. Conclusion. The capability of C60 fullerenes used alone to cause anti-inflammatory shift of microglia arginine metabolism makes them a promising agent for the correction neuroinflammatory processes involved in neurodegeneration. Potentiating action of C60 fullerene on immunomodulatory effect of Dox allows to consider C60 molecule as attractive vehicle for this antitumor agent.

Keywords: metabolism; c60; effect; c60 fullerene; microglial cells

Journal Title: Molecular pharmaceutics
Year Published: 2020

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