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Impact of whole‐body versus nose‐only inhalation exposure systems on systemic, respiratory, and cardiovascular endpoints in a 2‐month cigarette smoke exposure study in the ApoE −/− mouse model
Author(s) -
Kogel Ulrike,
Wong Ee Tsin,
Szostak Justyna,
Tan Wei Teck,
Lucci Francesco,
Leroy Patrice,
Titz Bjoern,
Xiang Yang,
Low Tiffany,
Wong Sin Kei,
Guedj Emmanuel,
Ivanov Nikolai V.,
Schlage Walter K.,
Peitsch Manuel C.,
Kuczaj Arkadiusz,
Vanscheeuwijck Patrick,
Hoeng Julia
Publication year - 2021
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.4149
Subject(s) - inhalation exposure , medicine , nicotine , lung , respiratory system , inhalation , physiology , endocrinology , toxicity , immunology , pathology , chemistry , anesthesia
Cigarette smoking is one major modifiable risk factor in the development and progression of chronic obstructive pulmonary disease and cardiovascular disease. To characterize and compare cigarette smoke (CS)‐induced disease endpoints after exposure in either whole‐body (WB) or nose‐only (NO) exposure systems, we exposed apolipoprotein E‐deficient mice to filtered air (Sham) or to the same total particulate matter (TPM) concentration of mainstream smoke from 3R4F reference cigarettes in NO or WB exposure chambers (EC) for 2 months. At matching TPM concentrations, we observed similar concentrations of carbon monoxide, acetaldehyde, and acrolein, but higher concentrations of nicotine and formaldehyde in NOEC than in WBEC. In both exposure systems, CS exposure led to the expected adaptive changes in nasal epithelia, altered lung function, lung inflammation, and pronounced changes in the nasal epithelial transcriptome and lung proteome. Exposure in the NOEC caused generally more severe histopathological changes in the nasal epithelia and a higher stress response as indicated by body weight decrease and lower blood lymphocyte counts compared with WB exposed mice. Erythropoiesis, and increases in total plasma triglyceride levels and atherosclerotic plaque area were observed only in CS‐exposed mice in the WBEC group but not in the NOEC group. Although the composition of CS in the breathing zone is not completely comparable in the two exposure systems, the CS‐induced respiratory disease endpoints were largely confirmed in both systems, with a higher magnitude of severity after NO exposure. CS‐accelerated atherosclerosis and other pro‐atherosclerotic factors were only significant in WBEC.