Abstract
Recently, there has been an outbreak of a condition named e-cigarette or vaping products-associated lung injury (EVALI). The primary components of vaping products include tetrahydrocannabinol (THC), vitamin E acetate (VEA) and medium-chain triglycerides (MCT), may be responsible for acute lung toxicity. Currently, little information is available on the physiological and biological effects of exposure to these products. We hypothesized that these CBD/counterfeit vape cartridges and their constituents (VEA and MCT) induce pulmonary toxicity, mediated by oxidative damage and inflammatory responses, leading to acute lung injury. We studied the potential mechanisms of CBD/counterfeit vape cartridge aerosol induced inflammatory response by evaluating the generation of reactive oxygen species by MCT, VEA, and cartridges and their effects on the inflammatory state of pulmonary epithelium and immune cells both in vitro and in vivo. Cells exposed to these aerosols generated reactive oxygen species, caused cytotoxicity, induced epithelial barrier dysfunction, and elicited an inflammatory response. Using a murine model, the parameters of acute toxicity to aerosol inhalation were assessed. Infiltration of neutrophils and lymphocytes was accompanied by significant increases in IL-6, eotaxin, and G-CSF in the bronchoalveolar lavage fluid (BALF). In mouse BALF, eicosanoid inflammatory mediators, leukotrienes, were significantly increased. Plasma from e-cig users also showed increased levels of hydroxyeicosatetraenoic acid (HETEs) and various eicosanoids. Exposure to CBD/counterfeit vape cartridge aerosols showed the most significant effects and toxicity compared to MCT and VEA. In addition, we determined SARS-CoV-2 related proteins and found no impact associated with aerosol exposures from these tested cartridges. Overall, this study demonstrates acute exposure to specific CBD/counterfeit vape cartridges induces in vitro cytotoxicity, barrier dysfunction, and inflammation and in vivo mouse exposure induces acute inflammation with elevated proinflammatory markers in the pathogenesis of EVALI.
Highlights
Electronic nicotine delivery systems (ENDS) products are battery-operated devices equipped with a tank, cartridge, or a pod filled with a liquid (e-liquid)
Both medium-chain triglycerides (MCT) and vitamin E acetate (VEA) induced a mild increase in IL-8 and Interleukin 6 (IL-6) compared to their unexposed controls
Lung homogenates from mice exposed to air, VEA, MCT, and CBD/counterfeit vape cartridge aerosols were quantified for lung surfactant protein A (SP-A)
Summary
Electronic nicotine delivery systems (ENDS) products are battery-operated devices equipped with a tank, cartridge, or a pod filled with a liquid (e-liquid). To assess the acute inhalation toxicity of MCT, VEA, and CBD/counterfeit vape cartridge aerosols in vivo, an acute exposure mouse model was utilized. In these exposed mouse groups, immune cell influx and cytokines in BALF were quantified to investigate the elicited inflammatory response compared to the unexposed counterparts. Lipidomics analyses performed on BALF of mice exposed to MCT, VEA, and CBD/counterfeit vape cartridge aerosols, as well as plasma of e-cig users, showed changes in eicosanoids, exhibiting their role in pulmonary inflammation. We hypothesized that VEA, MCT, and other chemical constituents present in CBD/counterfeit vape cartridges [8] cause cellular toxicity, and oxidative and inflammatory responses in epithelial cells, monocytes, and in vivo in mouse lung upon inhalation
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