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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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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113187/
https://www.ncbi.nlm.nih.gov/pubmed/33963423
http://dx.doi.org/10.1007/s00204-021-03020-4
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author 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
author_facet 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
author_sort Wong, Ee Tsin
collection PubMed
description 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. SUPPLEMENTARY INFORMATION: The online version supplementary material available at 10.1007/s00204-021-03020-4.
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spelling pubmed-81131872021-05-13 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 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 Arch Toxicol Organ Toxicity and Mechanisms 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. SUPPLEMENTARY INFORMATION: The online version supplementary material available at 10.1007/s00204-021-03020-4. Springer Berlin Heidelberg 2021-05-07 2021 /pmc/articles/PMC8113187/ /pubmed/33963423 http://dx.doi.org/10.1007/s00204-021-03020-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Organ Toxicity and Mechanisms
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
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 6-month inhalation toxicology study in apoe(−/−) mice demonstrates substantially lower effects of e-vapor aerosol compared with cigarette smoke in the respiratory tract
topic Organ Toxicity and Mechanisms
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113187/
https://www.ncbi.nlm.nih.gov/pubmed/33963423
http://dx.doi.org/10.1007/s00204-021-03020-4
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