Multi-endpoint analysis of human 3D airway epithelium following repeated exposure to whole electronic vapor product aerosol or cigarette smoke

被引:14
作者
Czekala, Lukasz [1 ]
Wieczorek, Roman [2 ]
Simms, Liam [1 ]
Yu, Fan [1 ]
Budde, Jessica [2 ]
Sticken, Edgar Trelles [2 ]
Rudd, Kathryn [1 ]
Verron, Thomas [1 ]
Brinster, Oleg [2 ]
Stevenson, Matthew [1 ]
Walele, Tanvir [1 ]
机构
[1] Imperial Brands PLC, 121 Winterstoke Rd, Bristol BS3 2LL, Avon, England
[2] Imperial Brands PLC Co, Reemtsma Cigarettenfabriken GmbH, Albert EinsteinRing 7, D-22761 Hamburg, Germany
来源
CURRENT RESEARCH IN TOXICOLOGY | 2021年 / 2卷
关键词
Cigarette; Electronic vapor product; Organotypic tissue model; Cilia; Immunohistochemistry; Pro-inflammatory markers; OBSTRUCTIVE PULMONARY-DISEASE; MODIFIED-RISK TOBACCO; IN-VITRO MODEL; LIQUID INTERFACE; MATRIX METALLOPROTEINASES; CILIA DYSFUNCTION; TNF-ALPHA; NICOTINE; DIFFERENTIATION; CULTURES;
D O I
10.1016/j.crtox.2021.02.004
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Smoking is a cause of serious diseases in smokers including chronic respiratory diseases. This study aimed to evaluate the tobacco harm reduction (THR) potential of an electronic vapor product (EVP, myblu (TM)) compared to a Kentucky Reference Cigarette (3R4F), and assessed endpoints related to chronic respiratory diseases. Endpoints included: cytotoxicity, barrier integrity (TEER), cilia function, immunohistochemistry, and pro-inflammatory markers. In order to more closely represent the user exposure scenario, we have employed the in vitro 3D organotypic model of human airway epithelium (MucilAir (TM), Epithelix) for respiratory assessment. The model was repeatedly exposed to either whole aerosol of the EVP, or whole 3R4F smoke, at the air liquid interface (ALI), for 4 weeks to either 30, 60 or 90 puffs on 3-exposure-per-week basis. 3R4F smoke generation used the ISO 20778:2018 regime and EVP aerosol used the ISO 20768:2018 vaping regime. Exposure to undiluted whole EVP aerosol did not trigger any significant changes in the level of proinflammatory mediators, cilia beating function, barrier integrity and cytotoxicity when compared with air controls. In contrast, exposure to diluted (1:17) whole cigarette smoke caused significant changes to all the endpoints mentioned above. To our knowledge, this is the first study evaluating the effects of repeated whole cigarette smoke and whole EVP aerosol exposure to a 3D lung model at the ALI. Our results add to the growing body of scientific literature supporting the THR potential of EVPs relative to combustible cigarettes and the applicability of the 3D lung models in human-relevant product risk assessments.
引用
收藏
页码:99 / 115
页数:17
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