Abstract
Electronic cigarette (e-cigarette) use has been linked to recent acute lung injury case clusters in over 2000 patients and dozens of deaths in the United States, however, the mechanism leading to lung injury is not certain although ultrafine particles, heavy metals, volatile organic compounds, and other harmful ingredients have been implicated. To systematically evaluate e-cigarette toxicity, we generated e-cigarette aerosols by varying the puff numbers (20–480), nicotine contents (0–24 mg/mL), and collected e-cigarette samples through an im**er system for biological assays. The calculated samples’ concentration ranged from 1.96 to 47.06 mg/mL. THP-1 monocyte-differentiated macrophages, BEAS-2B bronchial epithelial cells, wild-type C57BL/6 mice, and NF-κB-luc transgenic mice were used to test the effects of these samples. E-cigarette samples showed cytotoxicity to THP-1 cells and BEAS-2B in vitro, leading to increased oxidative stress, inflammatory cytokine production with or without nicotine, and cell death. Furthermore, aerosol generated from PG is more toxic than VG. The toxicity of e-cigarette samples is at least partially due to the reactive oxygen species and aldehydes, which are generated during the aerosolization processes by the e-cigarette device. After NF-κB-luc mice exposed with e-cigarette samples by oropharyngeal aspiration, NF-κB expressions were observed in a dose–response fashion with or without nicotine. In addition, the e-cigarette samples induced neutrophil infiltration, IL-1β production, oxidative stress marker heme oxygenase-1 expression in wild-type C57BL/6 mice. These results suggested that oxidative stress, pro-inflammatory NF-κB pathway activation, and cell death are involved in e-cigarette aerosol-induced acute lung inflammation.
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This study received support from the National Heart Lung and Blood Institute (Grant number: NHLBI R01 HL139379) (Y.Z).
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Conception and design of the work, the analysis and interpretation of data for the work, the drafting and revision of the manuscript, and approval of the final version to be published—TM, TX, and YZ; collection of data, the analysis and interpretation of data for the work, critical revision of key intellectual content, and approval of the final version to be published— TM, XW, LL, and BS.
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Ma, T., Wang, X., Li, L. et al. Electronic cigarette aerosols induce oxidative stress-dependent cell death and NF-κB mediated acute lung inflammation in mice. Arch Toxicol 95, 195–205 (2021). https://doi.org/10.1007/s00204-020-02920-1
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DOI: https://doi.org/10.1007/s00204-020-02920-1