C₆₀ Fullerene Governs Doxorubicin Effect on Metabolic Profile of Rat Microglial Cells In Vitro

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, because these cells, like other tissue resident phagocytes, are the 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 the 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 when used alone did not influence microglia oxidative metabolism and phagocytic activity but shifted arginine metabolism toward 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 of neuroinflammatory processes involved in neurodegeneration. The potentiating action of C₆₀ fullerene on the immunomodulatory effect of Dox allows us to consider the C₆₀ molecule as an attractive vehicle for this antitumor agent.