Harhaji, Ljubica (6507652139)Ljubica (6507652139)HarhajiIsakovic, Aleksandra (57202555421)Aleksandra (57202555421)IsakovicVucicevic, Ljubica (35333082000)Ljubica (35333082000)VucicevicJanjetovic, Kristina (35332184000)Kristina (35332184000)JanjetovicMisirkic, Maja (35332620200)Maja (35332620200)MisirkicMarkovic, Zoran (34968401700)Zoran (34968401700)MarkovicTodorovic-Markovic, Biljana (6602608361)Biljana (6602608361)Todorovic-MarkovicNikolic, Nadezda (12809125700)Nadezda (12809125700)NikolicVranjes-Djuric, Sanja (12809584300)Sanja (12809584300)Vranjes-DjuricNikolic, Zoran (7006320528)Zoran (7006320528)NikolicTrajkovic, Vladimir (7004516866)Vladimir (7004516866)Trajkovic2025-06-122025-06-122008https://doi.org/10.1007/s11095-007-9486-yhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-43149126321&doi=10.1007%2fs11095-007-9486-y&partnerID=40&md5=522eba6db32a35d21f6ab3a65de2fcdehttps://remedy.med.bg.ac.rs/handle/123456789/10788Purpose. The fullerene (C60/C70 mixture-C 60/70) nanocrystalline suspension prepared by solvent exchange method using tetrahydrofyran (THF/nC60/70) and polyhydroxylated C 60/70 [C60/70(OH)n] were compared for their ability to modulate cytotoxicity of the proinflammatory cytokine tumor necrosis factor (TNF). Materials and Methods. TNF-induced cytotoxicity was assessed in L929 fibrosarcoma cells by crystal violet assay. The type of cell death (apoptosis/necrosis), production of reactive oxygen species, mitochondrial depolarization and caspase activation were determined by flow cytometry using the appropriate reporter dyes. Results. THF/nC60/70 augmented, while C60/70(OH) n reduced the cytotoxicity of TNF. The numbers of cells undergoing apoptosis/necrosis, as well as of those displaying the activation of apoptosis-inducing enzymes of caspase family, were respectively increased or reduced by THF/nC60/70 or C60/70(OH) n. The antioxidant N-acetylcysteine and mitochondrial permeability transition inhibitor cyclosporin A each partly blocked the cytotoxic action of TNF, indicating the involvement of oxidative stress and mitochondrial dysfunction in the TNF cytotoxicity. Accordingly, THF/nC60/70 or C60/70(OH)n potentiated or suppressed, respectively, TNF-triggered oxidative stress and mitochondrial depolarization. Conclusion. The ability of different fullerene preparations to modulate TNF-induced oxidative stress and subsequent cell death suggests their potential value in the TNF-based cancer therapy or prevention of TNF-dependent tissue damage. © 2007 Springer Science+Business Media, LLC.ApoptosisFullereneNecrosisOxidative stressTumor necrosis factor