A 6-month inhalation toxicology study in Apoe−/− mice demonstrates substantially lower effects of e-vapor aerosol compared with cigarette smoke in the respiratory tract

Cigarette smoking is the major cause of chronic obstructive pulmonary disease. Considerable attention has been paid to the reduced harm potential of nicotine-containing inhalable products such as electronic cigarettes (e-cigarettes). We investigated the effects of mainstream cigarette smoke (CS) and...

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Bibliographic Details
Published in:	Archives of toxicology Vol. 95; no. 5; pp. 1805 - 1829
Main Authors:	Wong, Ee Tsin, Szostak, Justyna, Titz, Bjoern, Lee, Tom, Wong, Sin Kei, Lavrynenko, Oksana, Merg, Celine, Corciulo, Maica, Simicevic, Jovan, Auberson, Mehdi, Peric, Dariusz, Dulize, Remi, Bornand, David, Loh, Guo Jie, Lee, Kyeonghee Monica, Zhang, Jingjie, Miller, John H., Schlage, Walter K., Guedj, Emmanuel, Schneider, Thomas, Phillips, Blaine, Leroy, Patrice, Choukrallah, Mohamed Amin, Sierro, Nicolas, Buettner, Ansgar, Xiang, Yang, Kuczaj, Arkadiusz, Ivanov, Nikolai V., Luettich, Karsta, Vanscheeuwijck, Patrick, Peitsch, Manuel C., Hoeng, Julia
Format:	Journal Article
Language:	English
Published:	Berlin/Heidelberg Springer Berlin Heidelberg 01-05-2021 Springer Nature B.V
Subjects:	Aerosols Animals Apolipoprotein E Apolipoproteins E - metabolism Biomedical and Life Sciences Biomedicine Chronic obstructive pulmonary disease Cigarette smoke Cigarette smoking DNA methylation Electronic cigarettes Electronic Nicotine Delivery Systems Emphysema Environmental Health Exposure Female Flavor Flavors Gene expression Glycerol Inflammation Inhalation Inhalation Exposure Irritation Lung Lung diseases Lungs Mice Nicotiana - toxicity Nicotine Obstructive lung disease Occupational Medicine/Industrial Medicine Organ Toxicity and Mechanisms Oxidative stress Pharmacology/Toxicology Propylene Propylene glycol Proteomes Respiration Respiratory function Respiratory Function Tests Respiratory system Respiratory tract Smoke Smoking Tobacco Products Toxicology Transcriptome Transcriptomes Vapors Inflammation Emphysema Electronic cigarette Smoking COPD
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Summary:	Cigarette smoking is the major cause of chronic obstructive pulmonary disease. Considerable attention has been paid to the reduced harm potential of nicotine-containing inhalable products such as electronic cigarettes (e-cigarettes). We investigated the effects of mainstream cigarette smoke (CS) and e-vapor aerosols (containing nicotine and flavor) generated by a capillary aerosol generator on emphysematous changes, lung function, and molecular alterations in the respiratory system of female Apoe −/− mice. Mice were exposed daily (3 h/day, 5 days/week) for 6 months to aerosols from three different e-vapor formulations—(1) carrier (propylene glycol and vegetable glycerol), (2) base (carrier and nicotine), or (3) test (base and flavor)—or to CS from 3R4F reference cigarettes. The CS and base/test aerosol concentrations were matched at 35 µg nicotine/L. CS exposure, but not e-vapor exposure, led to impairment of lung function (pressure–volume loop area, A and K parameters, quasi-static elastance and compliance) and caused marked lung inflammation and emphysematous changes, which were confirmed histopathologically and morphometrically. CS exposure caused lung transcriptome (activation of oxidative stress and inflammatory responses), lipidome, and proteome dysregulation and changes in DNA methylation; in contrast, these effects were substantially reduced in response to the e-vapor aerosol exposure. Compared with sham, aerosol exposure (carrier, base, and test) caused a slight impact on lung inflammation and epithelia irritation. Our results demonstrated that, in comparison with CS, e-vapor aerosols induced substantially lower biological and pathological changes in the respiratory tract associated with chronic inflammation and emphysema.
ISSN:	0340-5761 1432-0738
DOI:	10.1007/s00204-021-03020-4