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

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.