Electronic cigarette solvents, pulmonary irritation, and endothelial dysfunction: role of acetaldehyde and formaldehyde
Electronic cigarette solvents, pulmonary irritation, and endothelial dysfunction: role of acetaldehyde and formaldehyde
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DOI：
10.1152/ajpheart.00878.2020
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发表时间：
2021-04-01
影响因子：
4.8
通讯作者：
Conklin, Daniel J.
中科院分区：
文献类型：
--
作者：
Jin, Lexiao;Lynch, Jordan;Conklin, Daniel J.
在美国使用电子烟(E-cig)十多年后，关于电子烟的使用和长期心肺疾病风险的不确定性依然存在。由于所有的电子烟都使用丙二醇和植物甘油(PG-VG)并产生丰富的饱和醛，小鼠通过吸入PG-VG衍生的气雾剂、甲醛(FA)、乙醛(AA)或过滤空气来暴露。暴露和心肺损伤的生物标志物通过质谱仪(尿代谢物)、放射性遥测(呼吸反射)、等长肌图(主动脉)和流式细胞仪(血液标志物)进行监测。与空气对照组相比，急性PG-VG暴露对肺反射(呼吸频率减慢，-50%)、内皮依赖性松弛(-61.8+/-4.2%)、白细胞减少(-47+/-7%)、红细胞(+6+/-1%)和血红蛋白(+4+/-1%)等多项生物标志物有显著影响。值得注意的是，FA暴露概括了PG-VG气雾剂对肺刺激反射和内皮功能障碍的显著影响，而AA暴露没有。为了尝试将PG-VG暴露与FA或AA暴露联系起来，采用GC-MS测定尿甲酸盐和醋酸盐水平。虽然FA和AA暴露都不会分别改变其主要代谢物甲酸盐或醋酸盐的排泄，但与空气暴露对照组相比，PG-VG气雾剂暴露显著增加暴露后尿醋酸酯，但不增加甲酸盐。这些数据表明，使用电子烟可能会增加心肺疾病的风险，而不是依赖于尼古丁和/或调味品的存在。这项研究表明，烟草产品衍生的气雾剂中的FA水平应该被调节到不会导致心肺损害的生物标志物的水平。仍然需要可靠的生物标志物来监测吸入的FA和AA.NEW&值得注意的是，使用电子烟(E-CIG)会导致健康人的内皮功能障碍(ED)，但E-CIG气雾剂中导致ED的特定成分尚不清楚。我们的研究表明，甲醛是在加热E-CIG溶剂(丙二醇，PG；植物甘油，VG)时形成的。单独暴露于甲醛或PG-VG气雾剂可刺激雌性小鼠的ED。由于ED不依赖尼古丁和调味剂，这些数据反映了使用PG-VG的电子烟的“普遍缺陷”。
After more than a decade of electronic cigarette (E-cig) use in the United States, uncertainty persists regarding E-cig use and long-term cardiopulmonary disease risk. As all E-cigs use propylene glycol and vegetable glycerin (PG-VG) and generate abundant saturated aldehydes, mice were exposed by inhalation to PG-VG-derived aerosol, formaldehyde (FA), acetaldehyde (AA), or filtered air. Biomarkers of exposure and cardiopulmonary injury were monitored by mass spectrometry (urine metabolites), radiotelemetry (respiratory reflexes), isometric myography (aorta), and flow cytometry (blood markers). Acute PG-VG exposure significantly affected multiple biomarkers including pulmonary reflex (decreased respiratory rate, -50%), endothelium-dependent relaxation (-61.8 +/- 4.2%), decreased WBC (-47 +/- 7%), and, increased RBC (+6 +/- 1%) and hemoglobin (+4 +/- 1%) versus air control group. Notably, FA exposure recapitulated the prominent effects of PG-VG aerosol on pulmonary irritant reflex and endothelial dysfunction, whereas AA exposure did not. To attempt to link PG-VG exposure with FA or AA exposure, urinary formate and acetate levels were measured by GC-MS. Although neither FA nor AA exposure altered excretion of their primary metabolite, formate or acetate, respectively, compared with air-exposed controls, PG-VG aerosol exposure significantly increased post-exposure urinary acetate but not formate. These data suggest that E-cig use may increase cardiopulmonary disease risk independent of the presence of nicotine and/or flavorings. This study indicates that FA levels in tobacco product-derived aerosols should be regulated to levels that do not induce biomarkers of cardiopulmonary harm. There remains a need for reliable biomarkers of exposure to inhaled FA and AA.NEW & NOTEWORTHY Use of electronic cigarettes (E-cig) induces endothelial dysfunction (ED) in healthy humans, yet the specific constituents in E-cig aerosols that contribute to ED are unknown. Our study implicates formaldehyde that is formed in heating of E-cig solvents (propylene glycol, PG; vegetable glycerin, VG). Exposure to formaldehyde or PG-VG-derived aerosol alone stimulated ED in female mice. As ED was independent of nicotine and flavorants, these data reflect a "universal flaw" of E-cigs that use PG-VG.