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.

Abstract

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.

• Authors: Ee Tsin Wong, Justyna Szostak, Bjoern Titz, Tom Lee, Sin Kei Wong, Oksana Lavrynenko, Celine Merg, Maica Corciulo, Jovan Simicevic, Mehdi Auberson, Dariusz Peric, Remi Dulize, David Bornand, Guo Jie Loh, Kyeonghee Monica Lee, Jingjie Zhang, John H Miller 4th, Walter K Schlage, Emmanuel Guedj, Thomas Schneider, Blaine Phillips, Patrice Leroy, Mohamed Amin Choukrallah, Nicolas Sierro, Ansgar Buettner, Yang Xiang, Arkadiusz Kuczaj, Nikolai V Ivanov, Karsta Luettich, Patrick Vanscheeuwijck, Manuel C Peitsch, Julia Hoeng
• Journal: Archives of toxicology (Arch Toxicol) Vol. 95 Issue 5 Pg. 1805-1829 (05 2021) ISSN: 1432-0738 [Electronic] Germany
• PMID: 33963423 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aerosols
• Apolipoproteins E
• Smoke
• Nicotine

Topics

• Aerosols
• Animals
• Apolipoproteins E (metabolism)
• Electronic Nicotine Delivery Systems
• Female
• Inhalation Exposure
• Lung
• Mice
• Nicotine
• Respiratory Function Tests
• Smoke
• Smoking
• Nicotiana (toxicity)
• Tobacco Products
• Transcriptome