The rapid assimilation of electronic nicotine delivery systems (e-cigarettes) into the consumer market since 2010 has necessitated an examination of their potential adverse health consequences, particularly given their widespread use among adolescents. While initially positioned as a lower-risk alternative to combustible tobacco, accumulating evidence suggests that e-cigarette use may precipitate deleterious cellular outcomes. Our study specifically focused on the toxicological effects induced by e-liquid exposure. We hypothesized that oxidative stress serves as a crucial mediator for the activation of cellular death pathways within pulmonary cells following nicotine exposure. Our primary objectives were to: 1) quantitatively assess the magnitude of nicotine-induced cytotoxicity, 2) delineate the underlying molecular signaling pathways responsible for nicotine-mediated cell demise, and 3) comparatively analyze these mechanisms against those induced by established pulmonary toxicants. This study utilized human pulmonary artery endothelial cells (HPAEC) as a model system to evaluate the cellular response to varying nicotine concentrations and exposure durations. Methodologies employed included cell culture techniques, ROS quantification assays, spectrophotometry, and microscopy to measure endpoints such as viability and cellular morphology. Our results demonstrate that nicotine exposure significantly impaired HPAEC proliferation and viability. Specifically, the growth rate of HPAEC was attenuated by approximately 3-fold in nicotine-exposed cells compared to untreated, normal control cells. Furthermore, between 30%-50% reduction in cell size was observed following both acute (time 0) and chronic (24 hour) nicotine exposures relative to untreated controls. Additionally, a significant dose and time-dependent increase in intracellular Reactive Oxygen Species (ROS) levels was detected following nicotine administration. This elevation was particularly pronounced at the 25 mg nicotine concentration during the 24-hour exposure period, with a 31% difference when compared to cells analyzed at time 0. Taken together, these findings confirm the onset of oxidative stress in HPAEC subsequent to nicotine exposure, as evidenced by the quantifiable accumulation of intracellular ROS. This oxidative mechanism has been critically implicated in cellular damage and the pathological progression of chronic disease states. Our data underscore the cytotoxic potential inherent in nicotine-containing e-liquids and the need for future research concerning their long-term physiological impact, particularly within vulnerable populations. Funding statement: This work is funded by a grant from The Nancy Cain and Jeffrey A. Marcus Science Endowment in Honor of President Donald A. Cowan (PI: Inimary Toby). This work is also funded in part by funding from the Pedlow Fund (PI: Inimary Toby). This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Picard et al. (2026) studied this question.