Combustion and Heated Tobacco Cigarettes, but Not E-Cigarettes, Impair Aquaporin-Dependent H2O2 Permeability in ATII-Like Cells

Cigarette smoke is a major inducer of oxidative stress, promoting reactive oxygen species (ROS) accumulation and contributing to the pathogenesis of chronic obstructive pulmonary disease (COPD) and lung cancer. Heated tobacco products (HTP) and e-cigarettes are promoted as reduced-risk alternatives; however, their impact on cellular redox regulation remains unclear. Here, we investigated the effects of conventional cigarette smoke extract (CSE), HTP, and e-cigarette extracts on hydrogen peroxide (H2O2) permeability mediated by aquaporins (peroxiporins) and on the activity of key antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase) in ATII-like cells. Eight aquaporins were detected at the mRNA level, and seven were confirmed at the protein level. CSE markedly inhibited H2O2 permeability across plasma, mitochondrial, and nuclear membranes. HTP extract impaired H2O2 transport across the plasma membrane and nuclear envelope, while mitochondrial permeability was preserved. Both CSE and HTP extract reduced superoxide dismutase and glutathione peroxidase activities. In contrast, e-cigarette extract exerted minimal effects on membrane H2O2 permeability and selectively decreased superoxide dismutase activity. Overall, our findings identify a graded pattern of oxidative toxicity (CSE > HTP > e-cigarette) and highlight peroxiporins as critical regulators of intracellular redox homeostasis. Although less harmful than cigarettes, alternative nicotine delivery systems are not biologically inert.