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Effects Of Functionalized Fullerenes On ROS Homeostasis Determine Their Cytoprotective Or Cytotoxic Properties

Svetlana V. Kostyuk, Elena V. Proskurnina, Ekaterina A. Savinova, Elizaveta S. Ershova, Olga A. Kraevaya, Larisa V. Kameneva, Pavel E. Umryukhin, Olga A. Dolgikh, Sergey I. Kutsev, Pavel A. Troshin, Natalia N. Veiko

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Background: Functionalized fullerenes (FF) can be considered regulators of intracellular reactive oxygen species (ROS) homeostasis; their direct oxidative damage—as well as regulation of oxidant enzymes and signaling pathways—should be considered. Methods: Uptake of two water-soluble functionalized C70 fullerenes with different types of aromatic addends (ethylphenylmalonate and thienylacetate) in human fetal lung fibroblasts, intracellular ROS visualization, superoxide scavenging potential, NOX4 expression, NRF2 expression, oxidative DNA damage, repair genes, cell proliferation and cell cycle were studied. Results & conclusion: The intracellular effects of ethylphenylmalonate C70 derivative (FF1) can be explained in terms of upregulated NOX4 activity. The intracellular effects of thienylacetate C70 derivative (FF2) can be probably resulted from its superoxide scavenging potential and inhibition of lipid peroxidation. FF1 can be considered a NOX4 upregulator and potential cytotoxicant and FF2, as a superoxide scavenger and a potential cytoprotector.