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 µg/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.

Mechanisms of toxic action of Ag, ZnO and CuO nanoparticles to selected ecotoxicological test organisms and mammalian cells in vitro: A comparative review

“…Induction of ROS in mammalian cells has been demonstrated also for CuO NPs. For example, addition of antioxidant N-acetylcysteine (NAC) mitigated the cytotoxicity of CuO NPs to human larynx epidermoid carcinoma cell line HEp-2 cells (Cho et al, 2012;Fahmy & Cormier, 2009).…”

Nanoparticles Toxicity and Their Routes of Exposures

“…This phenomenon is called oxidative stress. Knaapen et al [14] suggested three main factors which cause ROS release: (i) active redox cycling on the surface of NPs, particularly the metal-based NPs [15,16] (ii) oxidative groups functionalized on NPs; and (iii) particle-cell interactions, especially in the lungs where there is a rich pool of ROS producers like the inflammatory phagocytes, neutrophils and macrophages. Overproduction of ROS activates cytokines and upregulates interleukin (IL), kinases and tumor necrosis factor-α (TNF-α) as an indicators of proinflammatory signaling processes as a counter reaction to oxidative stress [17].…”

Safety Evaluation Study of Nanomaterials Aimed at Promoting Their Acceptance by Society

“…Many reports have indicated that intracellular generation of reactive oxygen species (ROS) is induced by various types of nanoparticles, such as carbon black, nanosized TiO2 and nano-sized silver particles (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41). Furthermore, it has recently been reported that crystalline silica induces intracellular ROS generation via NADPH oxidase activation following uptake by endocytosis (42,43).…”