Chemical Adducts of Reactive Flavor Aldehydes Formed in E-Cigarette Liquids Are Cytotoxic and Inhibit Mitochondrial Function in Respiratory Epithelial Cells.
Chemical Adducts of Reactive Flavor Aldehydes Formed in E-Cigarette Liquids Are Cytotoxic and Inhibit Mitochondrial Function in Respiratory Epithelial Cells.
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DOI：
10.1093/ntr/ntaa185
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发表时间：
2020-12-15
期刊：
影响因子：
--
通讯作者：
Jordt SE
中科院分区：
文献类型：
--
作者：
Jabba SV;Diaz AN;Erythropel HC;Zimmerman JB;Jordt SE
电子烟中的香料醛，包括香草醛、乙基香草醛（香草）和苯甲醛（浆果/水果），与电子液体溶剂、丙二醇和植物甘油（PG/VG）迅速发生化学反应，形成名为香料醛PG/VG缩醛的化学加合物，其可以有效地转移到电子烟气溶胶中。本研究的目的是比较缩醛及其母体醛在呼吸道上皮细胞中的细胞毒性和代谢毒性作用。在支气管（BEAS-2B）和肺泡（A549）上皮细胞中进行细胞代谢测定，评估苯甲醛、香草醛、乙基香草醛及其相应的PG缩醛对线粒体功能的关键生物能量参数的影响。在BEAS-2B细胞和原代人鼻上皮细胞（HNEpC）中使用活/死细胞试验分析苯甲醛和香草醛及其相应PG缩醛的潜在细胞毒性作用。在BEAS-2B细胞中使用Click-iT EDU细胞增殖测定比较香草醛和香草醛PG缩醛的细胞抑制作用。与它们的母体醛相比，PG缩醛降低了细胞能量代谢功能的关键参数，包括基础呼吸、三磷酸腺苷产生和备用呼吸能力。与苯甲醛相比，苯甲醛PG缩醛（1-10 mM）增加BEAS-2B和HNEpC中的细胞死亡率。香草醛PG缩醛在最高测试浓度下比香草醛更具细胞毒性，而两者均以浓度依赖性方式减少细胞增殖。在电子液体中形成的风味醛和溶剂化学品之间的反应产物具有与其母体风味醛不同的毒理学性质，并且可能有助于电子烟气雾剂在电子烟使用者的呼吸系统中的健康影响。由于没有可用的缩醛吸入毒性研究，本研究的数据将为使用体外和体内模型进行进一步毒理学研究提供基础。这项研究表明，制造商在生产时披露的电子烟液成分可能不足以为电子烟液和电子尼古丁输送系统的使用提供全面的风险评估，因为电子烟液随着时间的推移会产生化学不稳定性和新化合物的形成。
Flavor aldehydes in e-cigarettes, including vanillin, ethyl vanillin (vanilla), and benzaldehyde (berry/fruit), rapidly undergo chemical reactions with the e-liquid solvents, propylene glycol, and vegetable glycerol (PG/VG), to form chemical adducts named flavor aldehyde PG/VG acetals that can efficiently transfer to e-cigarette aerosol. The objective of this study was to compare the cytotoxic and metabolic toxic effects of acetals and their parent aldehydes in respiratory epithelial cells. Cell metabolic assays were carried out in bronchial (BEAS-2B) and alveolar (A549) epithelial cells assessing the effects of benzaldehyde, vanillin, ethyl vanillin, and their corresponding PG acetals on key bioenergetic parameters of mitochondrial function. The potential cytotoxic effects of benzaldehyde and vanillin and their corresponding PG acetals were analyzed using the LIVE/DEAD cell assay in BEAS-2B cells and primary human nasal epithelial cells (HNEpC). Cytostatic effects of vanillin and vanillin PG acetal were compared using Click-iT EDU cell proliferation assay in BEAS-2B cells. Compared with their parent aldehydes, PG acetals diminished key parameters of cellular energy metabolic functions, including basal respiration, adenosine triphosphate production, and spare respiratory capacity. Benzaldehyde PG acetal (1–10 mM) increased cell mortality in BEAS-2B and HNEpC, compared with benzaldehyde. Vanillin PG acetal was more cytotoxic than vanillin at the highest concentration tested while both diminished cellular proliferation in a concentration-dependent manner. Reaction products formed in e-liquids between flavor aldehydes and solvent chemicals have differential toxicological properties from their parent flavor aldehydes and may contribute to the health effects of e-cigarette aerosol in the respiratory system of e-cigarette users. With no inhalation toxicity studies available for acetals, data from this study will provide a basis for further toxicological studies using in vitro and in vivo models. This study suggests that manufacturers’ disclosure of e-liquid ingredients at time of production may be insufficient to inform a comprehensive risk assessment of e-liquids and electronic nicotine delivery systems use, due to the chemical instability of e-liquids over time and the formation of new compounds.
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DOI：
10.1164/rccm.201903-0615oc
发表时间：
2019-12-01
影响因子：
24.7
作者：
Ghosh, Arunava;Coakley, Raymond D.;Tarran, Robert
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DOI：
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发表时间：
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影响因子：
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DOI：
10.1152/ajplung.00389.2017
发表时间：
2018-11-01
影响因子：
4.9
作者：
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影响因子：
15.9
作者：
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