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 investigates the comparative effects of traditional cigarettes and e-cigarettes on lung health in male Rattus norvegicus over 8 and 12 weeks. Following ARRIVE 2.0 guidelines, 30 rats were divided into six groups to evaluate the impact of nicotine and ascorbic acid aerosols on tracheal and alveolar structures, as well as systemic inflammatory markers (IL-6, TNF-α, SOD-3, MDA). Results indicate that long-term cigarette exposure (12 weeks) and nicotine vaping (8 weeks) significantly stunted weight gain, whereas ascorbic acid vaping caused less growth inhibition. Histological analysis revealed that 8-week cigarette exposure (K3) increased tracheal mucosal thickness and antioxidant activity (SOD-3), while cigarette smoke generally decreased goblet cell counts and induced early emphysema. In contrast, long-term exposure significantly elevated IL-6 and caused severe alveolar wall damage. Notably, vaping ascorbic acid (K6) offered protective benefits, preserving the basement membrane and reducing septal thickening compared to nicotine groups. The findings conclude that while short-term smoking triggers immediate tracheal damage, long-term exposure escalates systemic inflammation and permanent alveolar destruction. Phytochemical-based aerosols, such as ascorbic acid, reduce pulmonary injury compared with nicotine-based products.