Temporal Effects of Cigarette Smoke and Phytochemical-Based E-Liquid Aerosols on Tracheo-Alveolar Histopathology and the IL-6/TNF-α Molecular Signaling Axis

This study compared the temporal effects of traditional cigarettes and e-cigarettes on lung health in male Rattus norvegicus over 8- and 12-week periods. Thirty rats were evaluated for tracheal/alveolar histopathology and systemic markers (IL-6, TNF-α, SOD-3, MDA). Chronic cigarette exposure (12 weeks) and nicotine aerosol (8 weeks) significantly suppressed weight gain, while ascorbic acid aerosol caused less growth inhibition. At 8 weeks, cigarette exposure (K3) induced adaptive tracheal mucosal thickening (66.88 ± 17.92 µm vs. 52.40 ± 2.63 µm in control K1), increased goblet cells (4.2 ± 2.44 N/mm), elevated SOD-3 (12.75 ± 1.10 pg/mL), and initiated emphysematous alveolar expansion (469.77 ± 91.31 µm vs. 202.03 ± 29.38 µm in K1 in K1). Conversely, 12-week cigarette smoke (K4) triggered epithelial exhaustion, significantly thinning the tracheal mucosa (34.65 ± 6.55 µm) and elevating systemic IL-6 (11.45 ± 1.17 pg/mL vs. 8.43 ± 0.88 pg/mL in control K2). Notably, chronic electronic ascorbic acid aerosolization (K6) preserved localized alveolar structural layouts and limited septal thickening compared with nicotine groups. However, it failed to suppress systemic inflammation, as evidenced by elevated IL-6 levels. In conclusion, while ascorbic acid aerosols moderate localized parenchymal destruction compared to nicotine, chronic aerosol exposure accelerates systemic immune activation.