The protection of cells from nitric oxide-mediated apoptotic death by mechanochemically synthesized fullerene (C(60)) nanoparticles.
The influence of fullerene (C(60)) nanoparticles on the cytotoxicity of a highly reactive free radical nitric oxide (NO) was investigated. Fullerene nanoparticles were prepared by mechanochemically assisted complexation with anionic surfactant sodium dodecyl sulfate, macrocyclic oligosaccharide gamma-cyclodextrin or the copolymer ethylene vinyl acetate-ethylene vinyl versatate. C(60) nanoparticles were characterized by UV-vis and atomic force microscopy. While readily internalized by mouse L929 fibroblasts, C(60) nanoparticles were not cytotoxic. Moreover, they partially protected L929 cells from the cytotoxic effect of NO-releasing compounds sodium nitroprusside (SNP), S-nitroso-N-acetylpenicillamine (SNAP), S-nitrosoglutathione (GSNO) and 3-morpholino-sydnonimine (SIN-1). C(60) nanoparticles reduced SNP-induced apoptotic cell death by preventing mitochondrial depolarization, caspase activation, cell membrane phosphatidylserine exposure and DNA fragmentation. The protective action of C(60) nanoparticles was not exerted via direct interaction with NO, but through neutralization of mitochondria-produced superoxide radical in NO-treated cells, as demonstrated by using different redox-sensitive reporter fluorochromes. These data suggest that C(60) complexes with appropriate host molecules might be plausible candidates for preventing NO-mediated cell injury in inflammatory/autoimmune disorders.
Misirkic
Maja S
MS
Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Dr. Subotica 1, 11000 Belgrade, Serbia.
Todorovic-Markovic
Biljana M
BM
Vucicevic
Ljubica M
LM
Janjetovic
Kristina D
KD
Jokanovic
Vukoman R
VR
Dramicanin
Miroslav D
MD
Markovic
Zoran M
ZM
Trajkovic
Vladimir S
VS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002474:Cell-Free System; D005609:Free Radicals / Q000378:metabolism; D037741:Fullerenes / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D009569:Nitric Oxide / Q000378:metabolism*
D005609:Free Radicals; D037741:Fullerenes; D009569:Nitric Oxide; C069837:fullerene C60