Reactive Oxygen Species, Mitochondrial Membrane Potential, and Cellular Membrane Potential Are Predictors of E-Liquid Induced Cellular Toxicity.
Reactive Oxygen Species, Mitochondrial Membrane Potential, and Cellular Membrane Potential Are Predictors of E-Liquid Induced Cellular Toxicity.
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DOI：
10.1093/ntr/ntaa177
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发表时间：
2020-12-15
期刊：
影响因子：
--
通讯作者：
Sassano MF
中科院分区：
文献类型：
--
作者：
Correia-Álvarez E;Keating JE;Glish G;Tarran R;Sassano MF
电子烟的口味对成年人和从不吸烟的年轻人很有吸引力。在过去十年中，消费迅速增长，仅在美国市场，就有超过8000种独特的口味。美国食品和药物管理局（FDA）已经开始对电子烟液体进行监管，但很多都没有经过测试，它们在细胞水平和对人体健康的影响仍不清楚。我们在人类细胞系HEK293T上测试了电子液体，并使用高通量筛选（HTS）方法测量了毒性、线粒体膜电位（ΔΨ m）、活性氧生成（ROS）和细胞膜电位（Vm）。我们的HTS工作包括单剂量和16点剂量反应曲线，允许平行测试≥90种市售电子液体，以提供快速的细胞效应评估，作为快速初步毒性方法的概念证明。并通过气相色谱-质谱联用分析了香精的化学成分。我们发现，电子液体导致ΔΨ m和Vm的减少，ROS的产生和毒性以剂量依赖性的方式增加。此外，五种特定化学成分的存在：香兰素、苯甲醇、乙托因、肉桂醛和甲基环戊烯诺酮，而不是尼古丁，与所研究的细胞性状的变化有关。我们的数据表明ΔΨ m、ROS、Vm和毒性可能表明电子烟液暴露后细胞死亡的程度。应该优先考虑对口味的影响进行进一步研究，以帮助FDA等政策制定者监管电子烟液体的成分。电子烟液的细胞毒性可以用适用于HTS的参数来预测。我们的数据表明ΔΨ m、ROS、Vm和毒性可能表明电子烟液暴露后细胞死亡的程度，这种毒性与化学成分有关，即调味成分。应该优先考虑对口味的影响进行进一步研究，以帮助FDA等政策制定者监管电子烟液体的成分。
The use of flavors in electronic cigarettes appeals to adults and never-smoking youth. Consumption has rapidly increased over the last decade, and in the U.S. market alone, there are over 8000 unique flavors. The U.S. Food and Drug Administration (FDA) has begun to regulate e-liquids, but many have not been tested, and their impact, both at the cellular level, and on human health remains unclear. We tested e-liquids on the human cell line HEK293T and measured toxicity, mitochondrial membrane potential (ΔΨ m), reactive oxygen species production (ROS), and cellular membrane potential (Vm) using high-throughput screening (HTS) approaches. Our HTS efforts included single-dose and 16-point dose–response curves, which allowed testing of ≥90 commercially available e-liquids in parallel to provide a rapid assessment of cellular effects as a proof of concept for a fast, preliminary toxicity method. We also investigated the chemical composition of the flavors via gas chromatography–mass spectrometry. We found that e-liquids caused a decrease in ΔΨ m and Vm and an increase in ROS production and toxicity in a dose-dependent fashion. In addition, the presence of five specific chemical components: vanillin, benzyl alcohol, acetoin, cinnamaldehyde, and methyl-cyclopentenolone, but not nicotine, were linked with the changes observed in the cellular traits studied. Our data suggest that ΔΨ m, ROS, Vm, and toxicity may be indicative of the extent of cell death upon e-liquid exposure. Further research on the effect of flavors should be prioritized to help policy makers such as the FDA to regulate e-liquid composition. E-liquid cellular toxicity can be predicted using parameters amenable to HTS. Our data suggest that ΔΨ m, ROS, Vm, and toxicity may be indicative of the extent of cell death upon e-liquid exposure, and this toxicity is linked to the chemical composition, that is, flavoring components. Further research on the effect of flavors should be prioritized to help policy makers such as the FDA to regulate e-liquid composition.
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DOI：
10.3390/ijerph111111192
发表时间：
2014-10-28
影响因子：
--
作者：
Bekki K;Uchiyama S;Ohta K;Inaba Y;Nakagome H;Kunugita N
通讯作者：
Kunugita N
影响因子：
10.4
作者：
Allen JG;Flanigan SS;LeBlanc M;Vallarino J;MacNaughton P;Stewart JH;Christiani DC
通讯作者：
Christiani DC
影响因子：
3.7
作者：
Hahn J;Monakhova YB;Hengen J;Kohl-Himmelseher M;Schüssler J;Hahn H;Kuballa T;Lachenmeier DW
通讯作者：
Lachenmeier DW
影响因子：
4.3
作者：
Du, Kuo;McGilll, Mitchell R.;Jaeschke, Hartmut
通讯作者：
Jaeschke, Hartmut
影响因子：
5.2
作者：
Behar, Rachel Z.;Luo, Wentai;Talbot, Prue
通讯作者：
Talbot, Prue