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Chromium(III) oxide nanoparticles induced remarkable oxidative stress and apoptosis on culture cells

Horie, Masanori, Nishio, Keiko, Endoh, Shigehisa, Kato, Haruhisa, Fujita, Katsuhide, Miyauchi, Arisa, Nakamura, Ayako, Kinugasa, Shinichi, Yamamoto, Kazuhiro, Niki, Etsuo, Yoshida, Yasukazu, Iwahashi, Hitoshi
Environmental toxicology 2013 v.28 no.2 pp. 61-75
apoptosis, carcinoma, cell viability, chromium, culture media, cytotoxicity, industrial applications, nanoparticles, oxidative stress, reactive oxygen species
Chromium(III) oxide (Cr₂O₃) is used for industrial applications such as catalysts and pigments. In the classical form, namely the fine particle, Cr₂O₃ is insoluble and chemically stable. It is classified as a low‐toxicity chromium compound. Recently, industrial application of nanoparticles (a new form composed of small particles with a diameter of ≤100 nm, in at least one dimension) has been increasing. Cellular effects induced by Cr₂O₃ nanoparticles are not known. To shed light upon this, the release of soluble chromium from Cr₂O₃ nano‐ and fine‐particles in culture medium was compared. Fine Cr₂O₃ particles were insoluble in the culture medium; on the contrary, Cr₂O₃ nanoparticles released soluble hexavalent chromium into the culture medium. Cr₂O₃ nanoparticles showed severe cytotoxicity. The effect of Cr₂O₃ nanoparticles on cell viability was higher than that of fine particles. Cr₂O₃ nanoparticles showed cytotoxicity equal to that of hexavalent chromium (K₂Cr₂O₇). Human lung carcinoma A549 cells and human keratinocyte HaCaT cells showed an increase in intracellular reactive oxygen species (ROS) level and activation of antioxidant defense systems on exposure to Cr₂O₃ nanoparticles. Exposure of Cr₂O₃ nanoparticles led to caspase‐3 activation, showing that the decrease in cell viability by exposure to Cr₂O₃ nanoparticles was caused by apoptosis. Cellular responses were stronger in the Cr₂O₃ nanoparticles‐exposed cells than in fine Cr₂O₃‐ and CrCl₃‐exposed cells. Cellular uptake of Cr₂O₃ particles were observed in nano‐ and fine‐particles. The cellular influence of the extracellular soluble trivalent chromium was lower than that of Cr₂O₃ nanoparticles. Cr₂O₃ nanoparticles showed cytotoxicity by hexavalent chromium released at outside and inside of cells. The cellular influences of Cr₂O₃ nanoparticles matched those of hexavalent chromium. In conclusion, Cr₂O₃ nanoparticles have a high cytotoxic potential. © 2011 Wiley Periodicals, Inc. Environ Toxicol 2013.