title: Copper oxide nanoparticles induce oxidative stress and cytotoxicity in airway epithelial cells.
abstract: Metal oxide nanoparticles are often used as industrial catalysts and elevated levels of these particles have been clearly demonstrated at sites surrounding factories. To date, limited toxicity data on metal oxide nanoparticles are available. To understand the impact of these airborne pollutants on the respiratory system, airway epithelial (HEp-2) cells were exposed to increasing doses of silicon oxide (SiO(2)), ferric oxide (Fe(2)O(3)) and copper oxide (CuO) nanoparticles, the leading metal oxides found in ambient air surrounding factories. CuO induced the greatest amount of cytotoxicity in a dose-dependent manner; while even high doses (400 microg/cm(2)) of SiO(2) and Fe(2)O(3) were non-toxic to HEp-2 cells. Although all metal oxide nanoparticles were able to generate ROS in HEp-2 cells, CuO was better able to overwhelm antioxidant defenses (e.g. catalase and glutathione reductase). A significant increase in the level of 8-isoprostanes and in the ratio of GSSG to total glutathione in cells exposed to CuO suggested that ROS generated by CuO induced oxidative stress in HEp-2 cells. Co-treatment of cells with CuO and the antioxidant resveratrol increased cell viability suggesting that oxidative stress may be the cause of the cytotoxic effect of CuO. These studies demonstrated that there is a high degree of variability in the cytotoxic effects of metal oxides, that this variability is not due to the solubility of the transition metal, and that this variability appears to involve sustained oxidative stress possibly due to redox cycling.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
authors.forename: Baher
authors.initials: B
authors.lastname: Fahmy
authors.forename: Stephania A
authors.initials: SA
authors.lastname: Cormier
mesh_terms: D002374:Catalase / Q000378:metabolism; D002460:Cell Line; D003300:Copper / Q000633:toxicity*; D003603:Cytotoxins / Q000633:toxicity*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005290:Ferric Compounds / Q000633:toxicity; D005980:Glutathione Reductase / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D053768:Metal Nanoparticles / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012822:Silicon Dioxide / Q000633:toxicity
chemical_list: D003603:Cytotoxins; D005290:Ferric Compounds; D017382:Reactive Oxygen Species; C000499:ferric oxide; C075750:8-epi-prostaglandin F2alpha; D012822:Silicon Dioxide; D003300:Copper; D015237:Dinoprost; D002374:Catalase; D005980:Glutathione Reductase; C030973:cupric oxide
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