Combined biological effects and lung proteomics analysis in mice reveal different toxic impacts of electronic cigarette aerosol and combustible cigarette smoke on the respiratory system

Combustible cigarettes produce many toxic substances that have been linked to diseases, such as lung cancer and chronic obstructive pulmonary disease. For those smokers unable or unwilling to quit, electronic cigarettes (e-cigarettes) could be used as an alternative to cigarettes. However, the effects and mechanisms of e-cigarette aerosol (ECA) on respiratory function have not been fully elucidated, and in vivo studies of its safety are limited compared to cigarette smoke (CS). In this article, we chose nicotine levels as dosing references and C57BL/6 mice for a 10-week subchronic inhalation toxicity study. A comprehensive set of toxicological endpoints was used to study the effect of exposure. Both CS (6 mg/kg) and ECA (6 or 12 mg/kg) inhalation had decreased the animal’s lung function and increased levels of inflammation markers, along with pathological changes in the airways and lungs, with ECA displaying a relatively small effect at the same dose. Proteomic analysis of lung tissue showed greater overall protein changes by CS than that of ECA, with more severe inflammatory network perturbations. Compared with ECA, KEGG analysis of CS revealed upregulation of more inflammatory and virus-related pathways. Protein–protein interactions (PPI) showed that both ECA and CS significantly changed ribosome and complement system-related proteins in mouse lung tissue. The results support that e-cigarette aerosol is less harmful to the respiratory system than cigarette smoke at the same dose using this animal model, thus providing additional evidence for the relative safety of e-cigarettes.