Electronic cigarette aerosols and copper nanoparticles induce mitochondrial stress and promote DNA fragmentation in lung fibroblasts

Abstract

Oxidants or nanoparticles have recently been identified as constituents of aerosols released from various styles of electronic cigarettes (E-cigs). Cells in the lung may be directly exposed to these constituents and harbor reactive properties capable of incurring acute cell injury. Our results show mitochondria are sensitive to both E-cig aerosols and aerosol containing copper nanoparticles when exposed to human lung fibroblasts (HFL-1) using an Air-Liquid Interface culture system, evident by elevated levels of mitochondrial ROS (mtROS). Increased mtROS after aerosol exposure is associated with reduced stability of an electron transport chain (ETC) complex IV subunit and nuclear DNA fragmentation. Increased levels of IL-8 and IL-6 in HFL-1 conditioned media were also observed. These findings reveal both mitochondrial, genotoxic, and inflammatory stresses are features of direct cell exposure to E-cig aerosols which are ensued by inflammatory duress, raising a concern on deleterious effect of vaping.

E-cigarettes and flavorings induce inflammatory and pro-senescence responses in oral epithelial cells and periodontal fibroblasts

“…We have recently shown oxidants/ROS reactivity from e-cig aerosols is comparable to conventional cigarette smoke [13, 14]. We show that e-cig flavoring caused protein oxidation as reflected in increased protein carbonylation.…”

“…Human gingival epithelium progenitors, (HGEPp; gingival epithelial cells) were grown in CnT-Prime medium (CnT-PR), epithelial culture medium as recommended by CELLnTEC Advanced Cell Systems. Transwell cultures were then placed into air-liquid interface (ALI) exposure chamber [14, 34]. BLU ® e-cigarette vapor (Classic Tobacco containing 16 mg nicotine or Magnificent Menthol flavor containing zero or 13–16 mg nicotine) was drawn into the ALI exposure chamber (2 puffs every 1 min), 4–5 second puff followed by 25 second pause for different time durations 5, 10, and 15 minutes respectively.…”

“…We have recently shown the comparable oxidants/reactive oxygen species (ROS) reactivity in e-cig aerosols compared to conventional cigarette smoke [13, 14]. Smoking tobacco contributes to the progression of periodontal disease [10].…”

Electronic cigarettes—A review of the physiological health effects

“…Nickel from the cartomizer is found in EC vapours at levels 2-100 times the amount found in cigarette smoke and can also contribute to lung inflammation (Williams et al 2013). Copper nanoparticles present in EC vapour can cause elevated levels of mitochondrial reactive oxygen species (ROS), DNA damage, and lung inflammation (Lerner et al 2016). In addition to introducing metals into the lungs, ECs contain oxidants in the batteries and cartomizers, which could also contribute to inflammation in the lungs (Lerner et al 2015a).…”

The roles of surface chemistry, dissolution rate, and delivered dose in the cytotoxicity of copper nanoparticles

“…The possibility of exposure to nanoparticles (NPs) has resulted in increasing research interests in understanding the detrimental effects on human health and the environment. 8–10 While in vitro studies have often been performed in assessing toxicity, the properties of NPs used are often not well defined, which results in inconsistent conclusions. Furthermore, understanding the behaviour of NPs in complex biological fluids is often challenging due to physicochemical changes, such as formation of protein corona, 11 dissolution, oxidation of surfaces, agglomeration and aggregation.…”