E-cigarette aerosols induce lower oxidative stress in vitro when compared to tobacco smoke.
Tobacco smoking is a risk factor for various diseases. The underlying cellular mechanisms are not fully characterized, but include oxidative stress, apoptosis, and necrosis. Electronic-cigarettes (e-cigarettes) have emerged as an alternative to and a possible means to reduce harm from tobacco smoking. E-cigarette vapor contains significantly lower levels of toxicants than cigarette smoke, but standardized methods to assess cellular responses to exposure are not well established. We investigated whether an in vitro model of the airway epithelium (human bronchial epithelial cells) and commercially available assays could differentiate cellular stress responses to aqueous aerosol extracts (AqE) generated from cigarette smoke and e-cigarette aerosols. After exposure to AqE concentrations of 0.063-0.500 puffs/mL, we measured the intracellular glutathione ratio (GSH:GSSG), intracellular generation of oxidant species, and activation of the nuclear factor erythroid-related factor 2 (Nrf2)-controlled antioxidant response elements (ARE) to characterize oxidative stress. Apoptotic and necrotic responses were characterized by increases in caspase 3/7 activity and reductions in viable cell protease activities. Concentration-dependent responses indicative of oxidative stress were obtained for all endpoints following exposure to cigarette smoke AqE: intracellular generation of oxidant species increased by up to 83%, GSH:GSSG reduced by 98.6% and transcriptional activation of ARE increased by up to 335%. Caspase 3/7 activity was increased by up to 37% and the viable cell population declined by up to 76%. No cellular stress responses were detected following exposure to e-cigarette AqE. The methods used were suitably sensitive to be employed for comparative studies of tobacco and nicotine products.
a Research and Development Center, British American Tobacco Plc , Southampton , UK.
Mark
M
Taylor
a Research and Development Center, British American Tobacco Plc , Southampton , UK.
Tony
T
Carr
a Research and Development Center, British American Tobacco Plc , Southampton , UK.
Oluwatobiloba
O
Oke
a Research and Development Center, British American Tobacco Plc , Southampton , UK.
Tomasz
T
Jaunky
a Research and Development Center, British American Tobacco Plc , Southampton , UK.
Damien
D
Breheny
a Research and Development Center, British American Tobacco Plc , Southampton , UK.
Frazer
F
Lowe
a Research and Development Center, British American Tobacco Plc , Southampton , UK.
Marianna
M
Gaça
D000336:Aerosols / Q000737:chemistry / Q000633:toxicity*; D001980:Bronchi / Q000166:cytology / Q000187:drug effects; D018929:Cell Culture Techniques; D002460:Cell Line; D066300:Electronic Nicotine Delivery Systems / Q000009:adverse effects*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D009538:Nicotine / Q000737:chemistry / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects*; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana
D000336:Aerosols; D012906:Smoke; D009538:Nicotine
Bronchial epithelial; cigarette smoke; e-cigarettes; in vitro; oxidative stress