Abstract
JUUL is a popular e-cigarette brand that manufactures e-liquids in a variety of flavors, such as mango and mint. Despite their popularity, the pulmonary effects of flavored JUUL e-liquids that are aerosolized and subsequently inhaled are not known. Therefore, the purpose of this study was to evaluate if acute exposure to JUUL e-cigarette aerosols in three popular flavors elicits an immunomodulatory or oxidative stress response in mice. We first developed a preclinical model that mimics human use patterns of e-cigarettes using 1 puff/min or 4 puffs/min exposure regimes. Based on cotinine levels, these exposures were representative of light/occasional and moderate JUUL users. We then exposed C57BL/6 mice to JUUL e-cigarette aerosols in mango, mint, and Virginia tobacco flavors containing 5% nicotine for 3 days, and assessed the inflammatory and oxidative stress response in the lungs and blood. In response to the 1 puff/min regime (light/occasional user), there were minimal changes in BAL cell composition or lung mRNA expression. However, at 4 puffs/min (moderate user), mint-flavored JUUL significantly increased lung neutrophils, while mango-flavored JUUL significantly increased Tnfα and Il13 mRNA in the lungs. Both the 1- and 4 puffs/min regimes significantly increased oxidative stress markers in the blood, indicating systemic effects. Thus, JUUL products are not inert; even short-term inhalation of flavored JUUL e-cigarette aerosols differentially causes immune modulation and oxidative stress responses.
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This work was supported by the Quebec Respiratory Health Research Network (QRHN) and the Canadian Institutes for Health Research (CIHR). C.J.B. is supported by a salary award from the Fonds de recherche du Quebec-Sante (FRQ-S). H.T. was supported by fellowships from the Réseau de recherche en santé réspiratoire du Québec (RSR) Scholarship and Meakins-Christie Laboratories. B.A. is supported by a Saudi Student Scholarship from the Ministry of Education (MOE).
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Data curation and/or analysis: TB, HT, SP, and BA; funding acquisition: KKM and CJB; investigation: TB, HT, and CJB; methodology: TB, HT, SP, BA; KKM, and CJB; project administration: KKM and CJB; resources: KKM and CJB; supervision: KKM and CJB; intellectual contributions: KKM, DHE, and CJB; manuscript writing, review, and editing: TB, HT, SP, BA, KKM, DHE, and CJB.
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Been, T., Traboulsi, H., Paoli, S. et al. Differential impact of JUUL flavors on pulmonary immune modulation and oxidative stress responses in male and female mice. Arch Toxicol 96, 1783–1798 (2022). https://doi.org/10.1007/s00204-022-03269-3
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DOI: https://doi.org/10.1007/s00204-022-03269-3