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. 2022 Jun;96(6):1783-1798.
doi: 10.1007/s00204-022-03269-3. Epub 2022 Mar 7.

Differential impact of JUUL flavors on pulmonary immune modulation and oxidative stress responses in male and female mice

Terek Been  1   2 , Hussein Traboulsi  2   3 , Sofia Paoli  1   2 , Bayan Alakhtar  4 , Koren K Mann  1   5 , David H Eidelman  2   3 , Carolyn J Baglole  6   7   8   9
Affiliations

Differential impact of JUUL flavors on pulmonary immune modulation and oxidative stress responses in male and female mice

Terek Been et al. Arch Toxicol. 2022 Jun.

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.

Keywords: Cotinine; Inflammation; JUUL; Lungs; Oxidative stress; e-Cigarette.

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