ORIGINAL RESEARCH article
Front. Toxicol.
Sec. In Vitro Toxicology
Volume 7 - 2025 | doi: 10.3389/ftox.2025.1624794
This article is part of the Research TopicApplication of New Approach Methodologies in Toxicological Assessment of Next Generation Tobacco and Nicotine ProductsView all 4 articles
Acetaldehyde and Methylglyoxal: Comparative Analysis of Toxic Electronic Cigarette Degradation Products in 3D and 2D Exposure Systems using Human Bronchial Epithelial Models
Provisionally accepted
- University of California, Riverside, United States
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Background: Acetaldehyde and methylglyoxal are structurally related aldehydes produced by thermal degradation of the electronic cigarette (EC) solvents, propylene glycol and glycerin. Despite their presence in EC aerosols, the biological effects of these aldehydes when inhaled during vaping are largely unknown. Methods: Three-dimensional (3D) human bronchial epithelial tissues (EpiAirway™) were exposed at the air liquid interface (ALI) to aerosols containing acetaldehyde or methylglyoxal at concentrations relevant to human vaping. PBS-exposed tissues served as controls. Comparative proteomic analyses were performed to assess global alterations in protein expression. Based on proteomics data, concentration-response experiments were conducted using BEAS-2B bronchial epithelial cells to evaluate reactive oxygen species, mitochondrial function, and cytoskeletal integrity. Results: ALI exposure to acetaldehyde or methylglyoxal resulted in 79 and 76 differentially expressed proteins (DEPs), respectively, with 51 overlapping proteins exhibiting similar fold change directionality. Ingenuity Pathway Analysis (IPA) Toxicity Lists identified key affected pathways, including mitochondrial dysfunction, fatty acid metabolism, G2/M DNA damage checkpoint regulation, and mitochondrial biogenesis. Gene Ontology (GO) ontology analysis revealed substantial overlap in affected biological processes and cellular components. Findings were further supported and expanded in BEAS-2B cell concentration-response assays, which confirmed mitochondrial impairment, elevated ROS levels, and disrupted cytoskeletal organization. Notably, TRPM8 inhibition attenuated methylglyoxal-induced mitochondrial dysfunction (MTT assay), while both TRPM8 and TRPA1 inhibition partially rescued actin depolymerization. Conclusions: Brief ALI exposure of EpiAirway™ tissues to vaping-relevant concentrations of acetaldehyde or methylglyoxal altered the bronchial epithelial proteome. Complementary concentration-response experiments with submerged BEAS-2B cells confirmed and extended the proteomics data. While both aldehydes exhibited similar proteomic and functional impacts, methylglyoxal was effective at substantially lower concentrations in all assays with some effects partially mediated via TRPA1 and TRPM8 channels. Keywords: Proteomics, Aldehydes, Acetaldehyde, Methylglyoxal, Bronchial Epithelium, Electronic Cigarettes
Keywords: Proteomics, Aldehydes, Acetaldehyde, methylglyoxal, Bronchial epithelium, electronic cigarettes
Received: 07 May 2025; Accepted: 09 Sep 2025.
Copyright: © 2025 Wong, Martinez, Hendricks and Talbot. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Prue Talbot, University of California, Riverside, United States
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