E-Cigarette Affects the Metabolome of Primary Normal Human Bronchial Epithelial Cells

Abstract

E-cigarettes are widely believed to be safer than conventional cigarettes and have been even suggested as aids for smoking cessation. However, while reasonable with some regards, this judgment is not yet supported by adequate biomedical research data. Since bronchial epithelial cells are the immediate target of inhaled toxicants, we hypothesized that exposure to e-cigarettes may affect the metabolome of human bronchial epithelial cells (HBEC) and that the changes are, at least in part, induced by oxidant-driven mechanisms. Therefore, we evaluated the effect of e-cigarette liquid (ECL) on the metabolome of HBEC and examined the potency of antioxidants to protect the cells. We assessed the changes of the intracellular metabolome upon treatment with ECL in comparison of the effect of cigarette smoke condensate (CSC) with mass spectrometry and principal component analysis on air-liquid interface model of normal HBEC. Thereafter, we evaluated the capability of the novel antioxidant tetrapeptide O-methyl-l-tyrosinyl-γ-l-glutamyl-l-cysteinylglycine (UPF1) to attenuate the effect of ECL. ECL caused a significant shift in the metabolome that gradually gained its maximum by the 5th hour and receded by the 7th hour. A second alteration followed at the 13th hour. Treatment with CSC caused a significant initial shift already by the 1st hour. ECL, but not CSC, significantly increased the concentrations of arginine, histidine, and xanthine. ECL, in parallel with CSC, increased the content of adenosine diphosphate and decreased that of three lipid species from the phosphatidylcholine family. UPF1 partially counteracted the ECL-induced deviations, UPF1’s maximum effect occurred at the 5th hour. The data support our hypothesis that ECL profoundly alters the metabolome of HBEC in a manner, which is comparable and partially overlapping with the effect of CSC. Hence, our results do not support the concept of harmlessness of e-cigarettes.

Identification of apoptosis‐associated protein factors distinctly expressed in cigarette smoke condensate‐exposed airway bronchial epithelial cells

“…Exposure to low concentrations of CSC increases the proliferation of NCI‐H292 cells, while exposure to high concentrations of CSC induces cytotoxicity [22] . Other studies using CSC at a dose of 10 µg/mL in the BEAS‐2B cell model have reported results highly consistent with ours [23,24] . Interestingly, our study indicates that CSC had no effect on cell necrosis.…”

Overview of Electronic Nicotine Delivery Systems: A Systematic Review

“…Cells Interleukins (IL) 227 Vascular endothelia growth factor 227 Tumor necrosis factor alpha (tnfa) 227 Monocyte chemotactic protein-1 227 Epidermal growth factor (EGF) 227 Ethylene (oxidative stress) 242 Metabolome alteration 268 sNox2-dp; 8-isoPGF2a, nitric oxide (NO) bioavailability, vitamin E, flow-mediated dilatation (FMD) (oxidative stress) 269 Intracellular glutathione (GSH) levels (oxidative stress) 279 Nicotinic acetylcholine receptor (α7 nAChR) 293 Hydrogen peroxide (H 2 O 2 ) (oxidative stress) 294 NFR2 localization (sign of oxidant-stress) 301 DNA damage 305 Cell cycle arrest 305 …”

Human lung epithelial cell cultures for analysis of inhaled toxicants: Lessons learned and future directions

“…Interestingly, comparative studies between epithelial cell lines (BEAS-2B and A549) and such differentiated ALI cultures show that these primary cultures may be more resistant to the toxic effects than cell lines . In addition to various studies using investigator-established ALI airway epithelial cell cultures (Zarcone et al, 2016;Aug et al, 2015), also these commercial ALI systems have been applied in in vitro toxicology studies (Reus et al, 2014;Kuper et al, 2015;Neilson et al, 2015). As an alternative to ALI culture, rotating bioreactors have been developed in which epithelial monolayers are alternately submerged in culture media or exposed to air on the apical side (Raredon et al, 2015).…”

“…Although an extensive discussion of the various read-outs is beyond the scope of this review, it needs to be stressed that a range of other parameters are currently assessed to determine the biological effect of an inhaled toxicant in in vitro cell culture systems. These include the various -omics techniques, as illustrated by the effect of electronic cigarette liquid on the metabolome of airway epithelial cells (Aug et al, 2015), markers of oxidative stress, induction of an oxidative stress response and inflammatory response (Zarcone et al, 2016;Zarcone et al, 2017;Kuper et al, 2015;Kooter et al, 2013), induction of the integrated stress response (Zarcone et al, 2016;Zarcone et al, 2017), impairment of autophagy (Shivalingappa et al, 2015), and impairment of epithelial antimicrobial defence (Amatngalim et al, 2017;Herr et al, 2009;Wu et al, 2014). Adsorption of test compounds can be specifically addressed by using radiolabeled substances that are applied via the apical surface, as demonstrated by Reus et al using the MucilAirTM model of differentiated human bronchial epithelial cells (Reus et al, 2014).…”