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Aerosols from electronic cigarettes contain substantially fewer of these dangerous byproducts, potentially reducing health risks. This study examined the potential of four different commercial nicotine-rich e-liquids to induce cytotoxicity and mitochondrial dysfunction and oxidative stress in human bronchial epithelial cells (H292), using air-liquid interface (ALI) exposure. In addition to a qualitative control of the e-liquids, by dosing contaminants, we assessed cell viability, apoptosis, mitochondrial membrane potential, and reactive oxygen species (ROS) generation, by comparing e-cig aerosols to 1R6F reference cigarette smoke. All tested e-liquids showed very low levels of trace metals and microplastics, with contaminant concentrations below WHO drinking water limits. Furthermore, e-liquid aerosol induced significantly reduced cytotoxicity compared to 1R6F regular cigarette smoke, and mitochondrial integrity was preserved. Furthermore, no ROS generation was observed when using flavored e-cigarette aerosol. These results provide evidence of the lower potential toxicity of e-cigarettes compared to tobacco cigarettes in an in vitro model simulating real-world smoke exposure.<\/jats:p>","DOI":"10.1007\/s11010-025-05430-9","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:43:33Z","timestamp":1763513013000},"page":"899-910","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mechanistic toxicity profiling of nicotine-rich e-liquids: mitochondrial and oxidative stress responses in ALI-exposed bronchial cells"],"prefix":"10.1007","volume":"481","author":[{"given":"Rosalia","family":"Emma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfio","family":"Distefano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Zuccarello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Copat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margherita","family":"Ferrante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gea Marzia","family":"Oliveri Conti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Pulvirenti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Carota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Campagna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Polosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Rust","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Caruso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Li Volti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,19]]},"reference":[{"issue":"9","key":"5430_CR1","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1080\/17476348.2019.1649146","volume":"13","author":"R Polosa","year":"2019","unstructured":"Polosa R, O\u2019Leary R, Tashkin D, Emma R, Caruso M (2019) The effect of e-cigarette aerosol emissions on respiratory health: a narrative review. 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In relation to his recent work in the area of respiratory diseases, clinical immunology, and tobacco control, Riccardo Polosa has received lecture fees and research funding from Pfizer, GlaxoSmithKline, CV Therapeutics, NeuroSearch A\/S, Sandoz, MSD, Boehringer Ingelheim, Novartis, Duska Therapeutics, and Forest Laboratories. Lecture fees from a number of European EC industry and trade associations (including FIVAPE in France and FIESEL in Italy) were directly donated to vaper advocacy no-profit organizations. Riccardo Polosa has also received grants from European Commission initiatives (U-BIOPRED and AIRPROM) and from the Integral Rheumatology & Immunology Specialists Network (IRIS) initiative. He has also served as a consultant for Pfizer, Global Health Alliance for treatment of tobacco dependence, CV Therapeutics, Boehringer Ingelheim, Novartis, Duska Therapeutics, ECITA (Electronic Cigarette Industry Trade Association, in the UK), Arbi Group Srl., Health Diplomats, and Sermo Inc. Riccardo Polosa has served on the Medical and Scientific Advisory Board of Cordex Pharma, Inc., CV Therapeutics, Duska Therapeutics Inc, Pfizer, and PharmaCielo. RP is also founder of the Center for Tobacco prevention and treatment (CPCT) at the University of Catania and of the Center of Excellence for the acceleration of Harm Reduction (CoEHAR) at the same University, which has received support from Foundation for a Smoke Free World to conduct 8 independent investigator-initiated research projects on harm reduction. Riccardo Polosa is currently involved in a patent application concerning an app tracker for smoking behaviour developed for ECLAT Srl. RP is also currently involved in the following pro bono activities: scientific advisor for LIAF, Lega Italiana Anti Fumo (Italian acronym for Italian Anti-Smoking League), the Consumer Advocates for Smoke-free Alternatives (CASAA) and the International Network of Nicotine Consumers Organizations (INNCO); Chair of the European Technical Committee for standardization on \u201cRequirements and test methods for emissions of electronic cigarettes\u201d (CEN\/TC 437; WG4). Giovanni Li Volti is currently elected Director of the Center of Excellence for the acceleration of HArm Reduction. The other authors have no relevant financial interests to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}