Dataset Information

Comparison between in vitro toxicities of tobacco- and menthol-flavored electronic cigarette liquids on human middle ear epithelial cells.

ABSTRACT: Since electronic-cigarettes (e-cigarettes) are considered less toxic than conventional tobacco smoking, the use of e-cigarettes has increased, and the market for e-cigarette liquids (e-liquids) is continuously increasing. However, many studies showed that e-cigarettes may cause various harmful effects in lung, oral and heart. In this study, we investigated the effects of e-liquids on otitis media (OM) using human middle ear epithelial cells (HMEECs). Menthol-flavored e-liquid induced significant cell death in HMEECs (IC50: 1.45?±?0.14%) and tobacco-flavored e-liquid led to increase in inflammatory cytokine levels and higher mucin production. Flavored e-liquids decreased the mRNA levels of genes encoding epithelial sodium channels (ENaCs) in HMEECs. Apoptosis and autophagy reactions were induced by exposure of HMEECs to menthol- and tobacco-flavored e-liquids. Tobacco-flavored e-liquids caused a greater increase in the levels of autophagosome marker, LC3-II, compared to menthol-flavored e-liquids, which was followed by cell death. These results demonstrate that flavored e-liquids cause cytotoxicity via apoptosis, autophagy, inflammatory response, and mucin production in HMEECs. The flavors present in e-liquids might be a risk factor for the development of otitis media.

SUBMITTER: Go YY

PROVIDER: S-EPMC7018737 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Comparison between in vitro toxicities of tobacco- and menthol-flavored electronic cigarette liquids on human middle ear epithelial cells.

Go Yoon Young YY Mun Ji Yoen JY Chae Sung-Won SW Chang Jiwon J Song Jae-Jun JJ

Scientific reports 20200213 1

Since electronic-cigarettes (e-cigarettes) are considered less toxic than conventional tobacco smoking, the use of e-cigarettes has increased, and the market for e-cigarette liquids (e-liquids) is continuously increasing. However, many studies showed that e-cigarettes may cause various harmful effects in lung, oral and heart. In this study, we investigated the effects of e-liquids on otitis media (OM) using human middle ear epithelial cells (HMEECs). Menthol-flavored e-liquid induced significant ...[more]

PMID: 32054887

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Project description:Electronic cigarettes (e-cigarettes) are the most widely used electronic nicotine delivery systems and are designed to imitate smoking and aid in smoking cessation. Although the number of e-cigarette users is increasing rapidly, especially among young adults and adolescents, the potential health impacts and biologic effects of e-cigarettes still need to be elucidated. Our previous study demonstrated the cytotoxic effects of electronic liquids (e-liquids) in a human middle ear epithelial cell (HMEEC-1) line, which were affected by the manufacturer and flavoring agents regardless of the presence of nicotine. In this study, we aimed to evaluate the gene expression profile and identify potential molecular modulator genes and pathways in HMEEC-1 exposed to two different e-liquids (tobacco- and menthol-flavored). HMEEC-1 was exposed to e-liquids, and RNA sequencing, functional analysis, and pathway analysis were conducted to identify the resultant transcriptomic changes. A total of 843 genes were differentially expressed following exposure to the tobacco-flavored e-liquid, among which 262 genes were upregulated and 581 were downregulated. Upon exposure to the menthol-flavored e-liquid, a total of 589 genes were differentially expressed, among which 228 genes were upregulated and 361 were downregulated. Among the signaling pathways associated with the differentially expressed genes mediated by tobacco-flavored e-liquid exposure, several key molecular genes were identified, including IL6 (interleukin 6), PTGS2 (prostaglandin-endoperoxide synthase 2), CXCL8 (C-X-C motif chemokine ligand 8), JUN (Jun proto-oncogene), FOS (Fos proto-oncogene), and TP53 (tumor protein 53). Under menthol-flavored e-liquid treatment, MMP9 (matrix metallopeptidase 9), PTGS2 (prostaglandin-endoperoxide synthase 2), MYC (MYC proto-oncogene, bHLH transcription factor), HMOX1 (heme oxygenase 1), NOS3 (nitric oxide synthase 3), and CAV1 (caveolin 1) were predicted as key genes. In addition, we identified related cellular processes, including inflammatory responses, oxidative stress and carcinogenesis, under exposure to tobacco- and menthol-flavored e-liquids. We identified differentially expressed genes and related cellular processes and gene signaling pathways after e-cigarette exposure in human middle ear cells. These findings may provide useful evidence for understanding the effect of e-cigarette exposure.

Project description:IntroductionSugars are major constituents and additives in traditional tobacco products, but little is known about their content or related toxins (formaldehyde, acetaldehyde, and acrolein) in electronic cigarette (e-cigarette) liquids. This study quantified levels of sugars and aldehydes in e-cigarette liquids across brands, flavors, and nicotine concentrations (n = 66).MethodsUnheated e-cigarette liquids were analyzed using liquid chromatography mass spectrometry and enzymatic test kits. Generalized linear models, Fisher's exact test, and Pearson's correlation coefficient assessed sugar, aldehyde, and nicotine concentration associations.ResultsGlucose, fructose and sucrose levels exceeded the limits of quantification in 22%, 53% and 53% of the samples. Sucrose levels were significantly higher than glucose [χ2(1) = 85.9, p < .0001] and fructose [χ2(1) = 10.6, p = .001] levels. Formaldehyde, acetaldehyde, and acrolein levels exceeded the limits of quantification in 72%, 84%, and 75% of the samples. Acetaldehyde levels were significantly higher than formaldehyde [χ2(1) = 11.7, p = .0006] and acrolein [χ2(1) = 119.5, p < .0001] levels. Differences between nicotine-based and zero-nicotine labeled e-cigarette liquids were not statistically significant for sugars or aldehydes. We found significant correlations between formaldehyde and fructose (-0.22, p = .004) and sucrose (-0.25, p = .002) and acrolein and fructose (-0.26, p = .0006) and sucrose (-0.21, p = .0006). There were no significant correlations between acetaldehyde and any of the sugars or any of the aldehydes and glucose.ConclusionsSugars and related aldehydes were identified in unheated e-cigarette liquids and their composition may influence experimentation in naïve users and their potential toxicity.ImplicationsThe data can inform the regulation of specific flavor constituents in tobacco products as a strategy to protect young people from using e-cigarettes, while balancing FDA's interest in how these emerging products could potentially benefit adult smokers who are seeking to safely quit cigarette smoking. The data can also be used to educate consumers about ingredients in products that may contain nicotine and inform future FDA regulatory policies related to product standards and accurate and comprehensible labeling of e-cigarette liquids.

Project description:Introduction:Flavors can mask the harshness of tobacco and make it appealing to young people. This study assessed flavored and menthol tobacco product sales at the national and state levels. Methods:Universal Product Code tobacco sales data collected by Nielsen were combined for convenience stores and all-outlets-combined during October 22, 2011-January 9, 2016. Products were characterized as flavored, menthol, or non-flavored/non-menthol. Total unit sales, and the proportion of flavored and menthol unit sales, were assessed nationally and by state for seven tobacco products. Joinpoint regression was used to assess trends in average monthly percentage change. Results:Nationally, the proportion of flavored and menthol sales in 2015 was as follows: cigarettes (32.5% menthol), large cigars (26.1% flavored), cigarillos (47.5% flavored, 0.2% menthol), little cigars (21.8% flavored, 19.4% menthol), chewing tobacco (1.4% flavored, 0.7% menthol), moist snuff (3.0% flavored, 57.0% menthol), and snus (88.5% menthol). From 2011 to 2015, sales increased for flavored cigarillos and chewing tobacco, as well as for menthol cigarettes, little cigars, moist snuff, and snus. Sales decreased for flavored large cigars, moist snuff, and snus, and for menthol chewing tobacco. State-level variations were observed by product; for example, flavored little cigar sales ranged from 4.4% (Maine) to 69.3% (Utah) and flavored cigarillo sales ranged from 26.6% (Maine) to 63.0% (Maryland). Conclusions:Menthol and flavored sales have increased since 2011, particularly for the products with the highest number of units sold, and significant state variation exists. Efforts to restrict flavored tobacco product sales could reduce overall U.S. tobacco consumption. Implications:Flavors in tobacco products can mask the harshness of tobacco and make these products more appealing to young people. This is the first study to assess national and state-level trends in flavored and menthol tobacco product sales. These findings underscore the importance of population-based interventions to address flavored tobacco product use at the national, state, and local levels. Additionally, further monitoring of flavored and menthol tobacco product sales can inform potential future regulatory efforts at the national, state, and local levels.

Project description:IntroductionFlavored tobacco sales restrictions (FTSRs) are implemented to reduce access to flavored tobacco products. We examined the association between seven cities with local FTSRs implemented in 2018/2019 and e-cigarette use among high school students in the California Bay Area.Aims and methodsWe analyzed data from the California Healthy Kids Survey using a difference-in-differences (D-I-D) strategy. We compared pre- and post-policy changes one year after implementation in current and ever e-cigarette use among students attending school in a city with a FTSR (exposed) (n = 20 832) versus without (unexposed) (n = 66 126). Other outcomes included ever marijuana use in an e-cigarette and ease of access to e-cigarettes.ResultsPre- to post-policy, the adjusted odds of current and ever e-cigarette use did not significantly change among students exposed and unexposed to a FTSR. In the adjusted D-I-D analysis, the odds of current (aOR: 1.25, 95% CI: 0.95, 1.65) and ever e-cigarette use (aOR: 1.06, 95% CI: 0.89, 1.26) did not significantly change by exposure group. However, one year post-implementation, the odds of ease of access to e-cigarettes significantly increased among exposed (aOR: 1.57, 95% CI: 1.27, 1.95) and unexposed students (aOR: 1.54, 95% CI: 1.39, 1.70). Similarly, the odds of ever using marijuana in an e-cigarette significantly increased among exposed (aOR: 1.35, 95% CI: 1.19, 1.53) and unexposed students (aOR: 1.29, 95% CI: 1.20, 1.39).ConclusionsLocal FTSRs in the California Bay Area were not associated with a change in e-cigarette use one year post-implementation. Increased ease of access and marijuana use may be explanatory factors.ImplicationsFTSRs were not associated with a decrease in current or ever e-cigarette use among high school students in the California Bay Area one-year post-implementation. Potential explanatory factors are that ease of access to e-cigarettes and using marijuana in an e-cigarette increased. More research is needed to understand the influence of these factors on youth access and behaviors. To address the youth e-cigarette epidemic, a comprehensive approach is needed, including policies, media campaigns, education programs, and cessation tools targeted to youth.

Dataset Information

Comparison between in vitro toxicities of tobacco- and menthol-flavored electronic cigarette liquids on human middle ear epithelial cells.

Publications

Comparison between in vitro toxicities of tobacco- and menthol-flavored electronic cigarette liquids on human middle ear epithelial cells.

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