Toxicity of copper oxide nanoparticles in lung epithelial cells exposed at the air–liquid interface compared with in vivo assessment

Abstract

The toxicity of spark-generated copper oxide nanoparticles (CuONPs) was evaluated in human bronchial epithelial cells (HBEC) and lung adenocarcinoma cells (A549 cells) using an in vitro air-liquid interface (ALI) exposure system. Dose-response results were compared to in vivo inhalation and instillation studies of CuONP. Cells were exposed to particle-free clean air (controls) or spark-generated CuONPs. The number median diameter, geometric standard deviation and total number concentration of CuONPs were 9.2 nm, 1.48 and 2.27×107 particles/cm3, respectively. Outcome measures included cell viability, cytotoxicity, oxidative stress and proinflammatory chemokine production. Exposure to clean air (2 or 4 hr) did not induce toxicity in HBEC or A549 cells. Compared with controls, CuONP exposures significantly reduced cell viability, increased lactate dehydrogenase (LDH) release and elevated levels of reactive oxygen species (ROS) and IL-8 in a dose-dependent manner. A549 cells were significantly more susceptible to CuONP effects than HBEC. Antioxidant treatment reduced CuONP-induced cytotoxicity. When dose was expressed per area of exposed epithelium there was good agreement of toxicity measures with murine in vivo studies. This demonstrates that in vitro ALI studies can provide meaningful data on nanotoxicity of metal oxides.

Rates of Hydroxyl Radical Production from Transition Metals and Quinones in a Surrogate Lung Fluid

“…This is consistent with previous studies of copper toxicity: (1) in vitro cellular assays show the Cu particles (especially nanoparticles) are remarkably toxic, likely because of ROS generation, 41-43 (2) in vivo animal studies generally show that inhaled and instilled particulate and soluble Cu cause adverse effects, 44-46 and (3) epidemiological studies reveal an association of ambient particulate Cu with adverse health effects and mortality in humans 47, 48 . Cu is known to be toxic, and is commonly used as a fungicide, pesticide, and preservative 49, 50 .…”

Applications of cell culture studies in pharmaceutical technology

“…Exposure of CuONP significantly reduced cell viability in a dose-dependent manner. CuONP were more toxic on A549 cells than HBEC 43 .…”

Metallic Nanoparticles, Toxicity Issues and Applications in Medicine

“…In a dose-dependent manner, CuO NPs exposure to cells has reduced the cell viability, increased lactate dehydrogenase release and increased ROS and IL-8 (Jing et al 2015). The toxicity of ZnO NPs at different concentrations of 5-25 μg/ml in HBEC has been determined to check the cell viability after 24 h of exposure (Heng et al 2010).…”