Exposure to the heated tobacco product IQOS generates apoptosis-mediated pulmonary emphysema in murine lungs
Exposure to the heated tobacco product IQOS generates apoptosis-mediated pulmonary emphysema in murine lungs
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DOI：
10.1152/ajplung.00215.2021
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发表时间：
2022-05-01
影响因子：
4.9
通讯作者：
Takahashi, Kazuhisa
中科院分区：
文献类型：
--
作者：
Nitta, Naoko Arano;Sato, Tadashi;Takahashi, Kazuhisa
肺气肿主要是由长期接触香烟烟雾(CS)引起的。新型烟草替代品，如加热烟草产品(HTPs)，已经成为香烟的更健康替代品。100s是日本最受欢迎的HTP，与传统香烟相比，它被宣传为无害。虽然一些研究已经报道了它的毒性，但很少进行体内研究。将12周龄C57BL6/J雄性小鼠随机分为3组，分别暴露于空气(对照组)、100s气雾剂和CS中6mo。暴露后，iQOS和CS组的体重增加与对照组相比显著受到抑制(4.93g；iQOS与AIR和5.504 g；CS与AIR)。100s组血清可替宁水平明显高于对照组。与对照组相比，IQOS组和CS组大鼠肺泡灌洗液中中性粒细胞和淋巴细胞计数明显增加。慢性IQOS暴露所致肺气肿与CS组相似。此外，在暴露于iQOS的小鼠的肺中，涉及细胞凋亡相关途径的基因的表达水平显著上调。细胞色素c、裂解caspase-3和裂解多聚(ADP-核糖)聚合酶-1在iQOS组较对照组高表达。与对照组相比，100s组单链DNA和TdT介导的dUTP缺口末端标记阳性的肺泡间隔细胞计数明显增加。总之，长期暴露在iQOS气雾剂中，主要通过与细胞凋亡相关的途径诱发肺气肿。这表明HTP并不是完全安全的烟草产品。
Pulmonary emphysema is predominantly caused by chronic exposure to cigarette smoke (CS). Novel tobacco substitutes, such as heated tobacco products (HTPs), have emerged as healthier alternatives to cigarettes. 100S, the most popular HTP in Japan, is advertised as harmless compared with conventional cigarettes. Although some studies have reported its toxicity, few in vivo studies have been conducted. Here, 12-wk-old C57BL6/J male mice were divided into three groups and exposed to air (as control), 100S aerosol, or CS for 6 mo. After exposure, the weight gain was significantly suppressed in the IQOS and CS groups compared with the control ( 4.93 g; IQOS vs. air and 5.504 g; CS vs. air). The serum cotinine level was significantly higher in the 100S group than in the control group. The neutrophils and lymphocyte count increased in the bronchoalveolar lavage fluid of the IQOS and CS groups compared with those in the control group. Chronic IQOS exposure induced pulmonary emphysema similar to that observed in the CS group. Furthermore, expression levels of the genes involved in the apoptosis-related pathways were significantly upregulated in the lungs of the IQOS-exposed mice. Cytochrome c, cleaved caspase-3, and cleaved poly (ADP-ribose) polymerase-1 were overexpressed in the IQOS group compared with the control. Single-stranded DNA and TdT-mediated dUTP nick-end labeling-positive alveolar septal cell count significantly increased in the 100S group compared with the control. In conclusion, chronic exposure to IQOS aerosol induces pulmonary emphysema predominantly via apoptosis-related pathways. This suggests that HTPs are not completely safe tobacco products.