Nicotine Affects Multiple Biological Processes in EpiDermTM Organotypic Tissues and Keratinocyte Monolayers

Pozuelos, Giovanna L.; Rubin, Matine A.; Vargas, Samantha; Ramírez, Erik; Bandaru, Dhiresh; Sha, Jihui; Wohlschlegel, James; Talbot, Prue

doi:10.3390/atmos13050810

Cited by 4 publications

(3 citation statements)

References 71 publications

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“…A study by Pozuelos et al examined the effect of nicotine on both keratinocyte cultures and a 3D model of human skin (EpiDermTM). The results showed that nicotine damages cellular organs, disrupts the homeostasis of reactive oxygen species, and causes oxidative damage to skin cells [ 25 ]. Likewise, Lee and colleagues examined the effects of nicotine on immortalized and malignant keratinocytes.…”

Section: Discussionmentioning

confidence: 99%

Nicotine Exerts Cytotoxic Effects in a Panel of Healthy Cell Lines and Strong Irritating Potential on Blood Vessels

Chioran

Sitaru

Macaşoi

et al. 2022

IJERPH

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The use of tobacco products is a major global public health issue, as it is the leading cause of preventable death worldwide. In addition, nicotine (NIC) is a key component of electronic and conventional cigarettes. Although nicotine’s addictive potential is well known, its health effects are not entirely understood. Thus, the main objective of the present study was to evaluate its toxicological profile both in vitro, at the level of three healthy cell lines, and in ovo, at the level of the chorioallantoic membrane. Five different concentrations of nicotine were used in keratinocytes, cardiomyocytes, and hepatocytes for the purpose of evaluating cell viability, cell morphology, and its impact on nuclei. Additionally, the hen’s egg test on the chorioallantoic membrane (HET-CAM) method was used to assess the biocompatibility and irritant potential of the chorioallantoic membrane. Across all cell lines studied, nicotine was proven to be significantly damaging to cell viability, with the highest concentration tested resulting in less than 2% viable cells. Moreover, the morphology of cells changed dramatically, with alterations in their shape and confluence. Nicotine-induced cell death appears to be apoptotic, based on its impact on the nucleus. In addition, nicotine was also found to have a very strong irritating effect on the chorioallantoic membrane. In conclusion, nicotine has an extremely strong toxicological profile, as demonstrated by the drastic reduction of cell viability and the induction of morphological changes and nuclear alterations associated with cellular apoptosis. Additionally, the HET-CAM method led to the observation of a strong irritating effect associated with nicotine.

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Section: Discussionmentioning

confidence: 99%

Nicotine Exerts Cytotoxic Effects in a Panel of Healthy Cell Lines and Strong Irritating Potential on Blood Vessels

Chioran

Sitaru

Macaşoi

et al. 2022

IJERPH

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“…Our EC participants used second generation products that can operate at high powers, which may have generated aerosols that were more toxic than those produced by low powered fourth generation ECs. However, fourth generation products, such as JUUL TM , contain high concentrations of nicotine (~60 mg/mL) [ 70 , 71 ], flavor chemicals, and coolants [ 72 ] that could affect gene expression and/or protein levels, as shown in other tissues [ 51 , 73 , 74 ] and may produce results that differ from the current study. A greater number of DEGs were identified in the EC vs. NS set than in the CS vs. NS and CS vs. EC sets, similar to several previous studies [ 17 , 18 ].…”

Section: Discussionmentioning

confidence: 83%

Transcriptomic Evidence That Switching from Tobacco to Electronic Cigarettes Does Not Reverse Damage to the Respiratory Epithelium

Pozuelos

Kagda

Rubin

et al. 2022

Toxics

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The health benefits of switching from tobacco to electronic cigarettes (ECs) are neither confirmed nor well characterized. To address this problem, we used RNA-seq analysis to compare the nasal epithelium transcriptome from the following groups (n = 3 for each group): (1) former smokers who completely switched to second generation ECs for at least 6 months, (2) current tobacco cigarette smokers (CS), and (3) non-smokers (NS). Group three included one former cigarette smoker. The nasal epithelial biopsies from the EC users vs. NS had a higher number of differentially expressed genes (DEGs) than biopsies from the CS vs. NS and CS vs. EC sets (1817 DEGs total for the EC vs. NS, 407 DEGs for the CS vs. NS, and 116 DEGs for the CS vs. EC comparison). In the EC vs. NS comparison, enriched gene ontology terms for the downregulated DEGs included cilium assembly and organization, whereas gene ontologies for upregulated DEGs included immune response, keratinization, and NADPH oxidase. Similarly, ontologies for cilium movement were enriched in the downregulated DEGs for the CS vs. NS group. Reactome pathway analysis gave similar results and also identified keratinization and cornified envelope in the upregulated DEGs in the EC vs. NS comparison. In the CS vs. NS comparison, the enriched Reactome pathways for upregulated DEGs included biological oxidations and several metabolic processes. Regulator effects identified for the EC vs. NS comparison were inflammatory response, cell movement of phagocytes and degranulation of phagocytes. Disease Ontology Sematic Enrichment analysis identified lung disease, mouth disease, periodontal disease and pulmonary fibrosis in the EC vs. NS comparison. Squamous metaplasia associated markers, keratin 10, keratin 13 and involucrin, were increased in the EC vs. NS comparison. Our transcriptomic analysis showed that gene expression profiles associated with EC use are not equivalent to those from non-smokers. EC use may interfere with airway epithelium recovery by promoting increased oxidative stress, inhibition of ciliogenesis, and maintaining an inflammatory response. These transcriptomic alterations may contribute to the progression of diseases with chronic EC use.

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“…Cellular morphology is a crucial aspect of cytotoxic evaluations, which involve assessing the toxic effects of various substances on living cells. Cellular morphology refers to the physical structure and shape of cells, and it plays a significant role in understanding the impact of cytotoxic agents [30]. Nicotine derived from electronic cigarettes induced a profound and concentration-dependent alteration in the morphology of human keratinocytes.…”

Section: Resultsmentioning

confidence: 99%

Comparative in Vitro and in Ovo Study of the Cytotoxic Profile of Nicotine From Electronic Cigarettes Versus Chewing Gum

DAN

2023

FARMACIA

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This study aimed to assess and compare the cytotoxic and vascular effects of e-liquid used in electronic cigarette (e-liquid) and nicotine containing chewing gum (NCG) using in vitro models of keratinocytes and cardiomyocytes, as well as in ovo models using the chorioallantoic membrane of developing chicken embryos. In the in vitro experiments, both cell lines were exposed to e-liquid and NCG at similar and relevant concentrations for in vivo administration. The results demonstrated that e-liquid exerted a more pronounced cytotoxic impact when compared to NCG. E-liquid caused a significant decrease in cell viability (up to about 46%) and induced substantial alterations in cellular morphology and nuclei. This finding implies an elevated risk linked to the use of electronic cigarettes, emphasizing that the cumulative content of harmful substances in these devices, beyond nicotine, contributes to their potential adverse effects. Additionally, in the in ovo evaluation, e-liquid revealed alarming signs of vascular irritation, including haemorrhage, lysis and intravascular coagulation within the chorioallantoic membrane. These findings underscore the vascular and skin health risks associated with e-liquid, prompting a need for comprehensive investigation into the long-term consequences for users. As a conclusion, the study outcomes highlight that, in vitro, the e-liquid used in electronic cigarette exerts heightened toxic effects on both keratinocytes and cardiomyocytes in comparison to the impact observed with nicotine containing chewing gum. RezumatPrezentul studiu și-a propus să evalueze și să compare efectele citotoxice și vasculare ale e-lichidului utilizat în țigări electronice (e-lichid) și guma de mestecat care conține nicotină (NCG) utilizând modele in vitro de keratinocite și cardiomiocite, precum și modele in ovo folosind membrana corioalantoică a embrionilor de pui. În experimentele in vitro, ambele linii celulare au fost expuse la e-lichid și NCG la concentrații similare și relevante pentru administrarea in vivo. Rezultatele au demonstrat că e-lichidul a exercitat un impact citotoxic mai pronunțat în comparație cu NCG. E-lichidul a provocat o scădere semnificativă a viabilității celulare (până la aproximativ 46%) și a indus modificări substanțiale în morfologia și nucleii celulelor. Această constatare indică un risc crescut asociat utilizării țigărilor electronice, evidențiind conținutul cumulativ de substanțe nocive din aceste dispozitive, nu doar de nicotină, care contribuie la potențialele lor efecte adverse. În plus, în evaluarea in ovo, e-liquid a indus semne alarmante de iritație vasculară, inclusiv hemoragie, liză și coagulare intravasculară în membrana corioalantoidiană. Aceste constatări subliniază riscurile pentru sănătatea vasculară și a pielii asociate cu lichidul din țigările electronice, accentuând necesitatea unei investigații ample a consecințelor pe termen lung pentru utilizatori. În concluzie, rezultatele studiului evidențiază că, in vitro, lichidul provenit de la țigările electronice exe...

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Nicotine Affects Multiple Biological Processes in EpiDermTM Organotypic Tissues and Keratinocyte Monolayers

Cited by 4 publications

References 71 publications

Nicotine Exerts Cytotoxic Effects in a Panel of Healthy Cell Lines and Strong Irritating Potential on Blood Vessels

Nicotine Exerts Cytotoxic Effects in a Panel of Healthy Cell Lines and Strong Irritating Potential on Blood Vessels

Transcriptomic Evidence That Switching from Tobacco to Electronic Cigarettes Does Not Reverse Damage to the Respiratory Epithelium

Comparative in Vitro and in Ovo Study of the Cytotoxic Profile of Nicotine From Electronic Cigarettes Versus Chewing Gum

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