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E-Cigarette Liquids and Aldehyde Flavoring Agents Inhibit CYP2A6 Activity in Lung Epithelial Cells
Citation:
Winters, B., P. Clapp, S. Simmons, T. Kochar, I. Jaspers, AND M. Madden. E-Cigarette Liquids and Aldehyde Flavoring Agents Inhibit CYP2A6 Activity in Lung Epithelial Cells. ACS Omega. American Chemical Society, Washington, DC, 8(12):11261-11266, (2023). https://doi.org/10.1021/acsomega.2c08258
Impact/Purpose:
A subset of e-cigarette liquids (e-liquids) and common e-liquid flavoring agents were previously shown to inhibit microsomal recombinant cytochrome P450 2A6 (CYP2A6), the enzyme primarily responsible for the metabolism of nicotine to cotinine. The overarching concern of CYP2A6 inhibition by e-liquids and flavoring agents is the potential for reduced metabolism of nicotine present in most e-liquids. Previous research has identified multiple cases where pharmaceuticals, environmental agents, or cigarette additives have inhibited CYP2A6, resulting in a drug–drug interaction that ultimately can increase serum nicotine levels. A cell-based assay to screen for perturbation of CYP2A6 by e-liquids and reactive flavoring agents is valuable as it addresses data gaps on the ability of flavoring agents, specifically reactive aromatic aldehydes, to enter cells and target CYP2A6 at the ER. Thus, a cell-based assay may provide more biologically relevant pharmacokinetic parameters such as the half-maximal inhibition concentration (IC50) than those previously derived using recombinant microsomal CYP2A6.
Description:
Certain e-liquids and aromatic aldehyde flavoring agents were previously identified as inhibitors of microsomal recombinant CYP2A6, the primary nicotine-metabolizing enzyme. However, due to their reactive nature, aldehydes may react with cellular components before reaching CYP2A6 in the endoplasmic reticulum. To determine whether e-liquid flavoring agents inhibited CYP2A6 in a cellular system, we investigated their effects on CYP2A6 using BEAS-2B cells transduced to overexpress CYP2A6. We demonstrated that two e-liquids and three aldehyde flavoring agents (cinnamaldehyde, benzaldehyde, and ethyl vanillin) exhibited dose-dependent inhibition of cellular CYP2A6.
URLs/Downloads:
DOI: E-Cigarette Liquids and Aldehyde Flavoring Agents Inhibit CYP2A6 Activity in Lung Epithelial Cells
https://pubmed.ncbi.nlm.nih.gov/37008141/