Pulmonary immune response regulation, genotoxicity, and metabolic reprogramming by menthol- and tobacco-flavored e-cigarette exposures in mice

• DOI: 10.1093/toxsci/kfad033
• Publication Date: 2023-04-13T15:37:24Z
• Authors: Thivanka Muthumalage; Irfan Rahman
• Keywords: Mice, Inbred C57BL; Aerosols; Flavoring Agents; Mice; Menthol; Phosphatidylinositol 3-Kinases; Nicotine; Animals; Tobacco Products; Electronic Nicotine Delivery Systems; Lung; 3. Good health

Abstract Menthol and tobacco flavors are available for almost all products, including electronic cigarettes (e-cigs). These a mixture of chemicals with overlapping constituents. There no comparative toxicity studies these produced by different manufacturers. We hypothesized that acute exposure to menthol tobacco-flavored e-cig aerosols induces inflammatory, genotoxicity, metabolic responses in mouse lungs. compared two brands, A B, (PG/VG, menthol, tobacco) without nicotine their inflammatory response, genotoxic markers, altered genes proteins the context metabolism exposing strains, C57BL/6J (Th1-mediated) BALB/cJ (Th2-mediated). Brand nicotine-free caused increased neutrophils differential T-lymphocyte influx bronchoalveolar lavage fluid induced significant immunosuppression, while brand elicited an allergic response Eotaxin, IL-6, RANTES levels. B similar flavor exposure. Upon exposure, genotoxicity markers significantly lung tissue. were associated NLRP3 inflammasome TRPA1 induction flavor. Nicotine decreased surfactant protein D PAI-1 flavors, respectively. Integration pathway gene expression analysis showed immunometabolic regulation T cells via PI3K/Akt/p70S6k-mTOR axis suppressed immunity/allergic immune response. Overall, this study flavored aerosols, unraveling potential signaling pathways flavor-mediated pulmonary toxicological responses, emphasized need standardized testing appropriate premarket authorization e-cigarette products.