Fullerene: biomedical engineers get to revisit an old friend

Protective effects of fullerenol C60(OH)24 against doxorubicin-induced cardiotoxicity and hepatotoxicity in rats with colorectal cancer.

Fullerenol cytotoxicity in kidney cells is associated with cytoskeleton disruption, autophagic vacuole accumulation, and mitochondrial dysfunction.

Background The purpose of this study was to investigate the mechanism of noxious effects of amorphous silica nanoparticles on human endothelial cells. Methods Nanoparticle uptake was examined by transmission electron microscopy. Electrochemical nanosensors were used to measure the nitric oxide (NO) and peroxynitrite (ONOO(-)) released by a single cell upon nanoparticle stimulation. The downstream inflammatory effects were measured by an enzyme-linked immunosorbent assay, real-time quantitative polymerase chain reaction, and flow cytometry, and cytotoxicity was measured by lactate dehydrogenase assay. Results We found that the silica nanoparticles penetrated the plasma membrane and rapidly stimulated release of cytoprotective NO and, to a greater extent, production of cytotoxic ONOO(-). The low [NO]/[ONOO(-)] ratio indicated increased nitroxidative/oxidative stress and correlated closely with endothelial inflammation and necrosis. This imbalance was associated with nuclear factor κB activation, upregulation of key inflammatory factors, and cell death. These effects were observed in a nanoparticle size-dependent and concentration-dependent manner. Conclusion The [NO]/[ONOO(-)] imbalance induced by amorphous silica nanoparticles indicates a potentially deleterious effect of silica nanoparticles on vascular endothelium.

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Amorphous silica nanoparticles trigger nitric oxide/peroxynitrite imbalance in human endothelial cells: inflammatory and cytotoxic effects

The fullerene C60, due to the physicochemical properties of its spherical cage-like molecule build exclusively from carbon atoms, is able to both scavenge and generate reactive oxygen species. While this unique dual property could be exploited in biomedicine, the low water solubility of C60 hampers the investigation of its behavior in biological systems. The C60 can be brought into water by solvent extraction, by complexation with surfactants/polymers, or by long-term stirring, yielding pristine (unmodified) fullerene suspensions. On the other hand, a modification of the C60 core by the attachment of various functional groups results in the formation of water-soluble fullerene derivatives. Assessment of toxicity associated with C60 preparations is of pivotal importance for their biomedical application as cytoprotective (antioxidant), cytotoxic (anticancer), or drug delivery agents. Moreover, the widespread industrial utilization of fullerenes may also have implications for human health. However, the alterations in physicochemical properties imposed by the utilization of different methods for C60 solubilization profoundly influence toxicological effects of fullerene preparations, thus making the analysis of their potential therapeutic and environmental toxicity difficult. This review provides a comprehensive evaluation of the in vitro and in vivo toxicity of fullerenes, focusing on the comparison between pristine and derivatized C60 preparations and the mechanisms of their toxicity to mammalian cells and tissues.

Toxicity of pristine versus functionalized fullerenes: mechanisms of cell damage and the role of oxidative stress

We studied the effects of a C60 water suspension at 4 microg/mL (nC60) and the water soluble fullerenol C60(OH)24 at final concentrations of 1-100 microg/mL on human umbilical vein endothelial cells (HUVECs) in culture. We found that a 24 hr treatment of HUVECs with C60(OH)24 at 100 microg/mL significantly increased cell surface expression of ICAM-1(CD54) (67 +/- 4% CD54+ cells vs. 19 +/- 2 % CD540 cells in control; p < 0.001). In addition, this treatment induced the expression of tissue factor (CD142) on HUVECs (54 +/- 20% CD142+ cells vs 4 +/- 2% CD142+ cells in control; p = 0.008) and increased exposure of phosphatidylserine (PS) (29 +/- 2% PS+ cells vs. 12 +/- 5% PS+ cells in control; p < 0.001). Analysis of cell cycle and DNA fragmentation (TUNEL) showed that both nC60 and C60(OH)24 caused G1 arrest of HUVECs and C60(OH)24 induced significant apoptosis (21 +/- 2% TUNEL+ cells at 100 microg/mL of C60(OH)24 vs. 4 +/- 2% TUNEL+ cells in control; p < 0.001). We also demonstrated that both nC60 and C60(OH)24 induced a rapid concentration dependent elevation of intracellular calcium [Ca2+]i. This could be inhibited by EGTA, suggesting that the source of [Ca2+]i in fullerene stimulated calcium flux is predominantly from the extracellular environment. In conclusion, fullerenol C60(OH)24 had both pro-inflammatory and pro-apoptotic effects on HUVECs, indicating possible adverse effects of fullerenes on the endothelium.

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Adverse effects of fullerenes on endothelial cells: fullerenol C60(OH)24 induced tissue factor and ICAM-I membrane expression and apoptosis in vitro.

https://www.dovepress.com/getfile.php?fileID=2276

Adverse Effects of Fullerenes on Endothelial Cells: Fullerenol C60(OH)24 Induced Tissue Factor and ICAM-1 Membrane Expression and Caused Apoptosis In Vitro.

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Relationships between the Frequency of Family Meals, Overweight, Dietary Intake and TV Viewing Behaviors among White, Hispanic, and Black Maryland Adolescent Girls

Sheena F. Siddiqui

Papers

Adverse effects of fullerenes on endothelial cells: fullerenol C60(OH)24 induced tissue factor and ICAM-I membrane expression and apoptosis in vitro.

Adverse Effects of Fullerenes on Endothelial Cells: Fullerenol C60(OH)24 Induced Tissue Factor and ICAM-1 Membrane Expression and Caused Apoptosis In Vitro.

Relationships between the Frequency of Family Meals, Overweight, Dietary Intake and TV Viewing Behaviors among White, Hispanic, and Black Maryland Adolescent Girls