Roberts, Joan E. and Wielgus, Albert R. and Boyes, William K. and Andley, Usha and Chignell, Colin F. (2008) Phototoxicity and cytotoxicity of fullerol in human lens epithelial cells. Toxicology and applied pharmacology, 228 (1). pp. 49-58. ISSN 0041-008X
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The water-soluble, hydroxylated fullerene [fullerol, nano-C60(OH)22-26] has several clinical applications including use as a drug carrier to bypass the blood ocular barriers. We have assessed fullerol's potential ocular toxicity by measuring its cytotoxicity and phototoxicity induced by UVA and visible light in vitro with human lens epithelial cells (HLE B-3). Accumulation of nano-C60(OH)22-26 in the cells was confirmed spectrophotometrically at 405 nm and cell viability estimated using MTS and LDH assays. Fullerol was cytotoxic to HLE B-3 cells maintained in the dark at concentrations higher than 20 microM. Exposure to either UVA or visible light in the presence of >5 microM fullerol-induced phototoxic damage. When cells were pretreated with non-toxic antioxidants: 20 microM lutein, 1 mM N-acetyl cysteine, or 1 mM l-ascorbic acid prior to irradiation, only the singlet oxygen quencher-lutein significantly protected against fullerol photodamage. Apoptosis was observed in lens cells treated with fullerol whether or not the cells were irradiated, in the order UVA>visible light>dark. Dynamic light scattering (DLS) showed that in the presence of the endogenous lens protein alpha-crystallin, large aggregates of fullerol were reduced. In conclusion, fullerol is both cytotoxic and phototoxic to human lens epithelial cells. Although the acute toxicity of water-soluble nano-C60(OH)22-26 is low, these compounds are retained in the body for long periods, raising concern for their chronic toxic effect. Before fullerols are used to deliver drugs to the eye, they should be tested for photo- and cytotoxicity in vivo.
|Additional Information:||Article Outline Introduction Materials and methods Reagents Cell culture In vitro uptake studies of fullerol in HLE B-3 cells Ex vivo uptake studies of fullerol UVA/visible light treatment Phototoxicity inhibition studies MTS and LDH assays Measurement of apoptotic and necrotic cells Caspase-3 activity Particle size measurements Statistical analysis Results In vitro and ex vivo uptake of fullerol into lens tissues Photo- and cytotoxicity of fullerol to lens cells Inhibition of fullerol phototoxicity to lens cells Analysis of fullerol-induced apoptosis and necrosis Interaction of fullerol with α-crystallin Discussion Implications for human health Conclusion Acknowledgements References|
|Uncontrolled Keywords:||Fullerenes; Fullerol; Ocular toxicology; Phototoxicity; Human lens epithelial cells; Dynamic light scattering|
|Subjects:||Risk > Environment, health and safety aspects of nanotechnology|
|Deposited By:||Lesley Tobin|
|Deposited On:||29 Oct 2008 16:39|
|Last Modified:||19 Feb 2009 10:09|
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