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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.

ABSTRACT: 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.

SUBMITTER: Kogel U

PROVIDER: S-EPMC8519037 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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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<sup>-/-</sup> mouse model.

Kogel Ulrike U Wong Ee Tsin ET Szostak Justyna J Tan Wei Teck WT Lucci Francesco F Leroy Patrice P Titz Bjoern B Xiang Yang Y Low Tiffany T Wong Sin Kei SK Guedj Emmanuel E Ivanov Nikolai V NV Schlage Walter K WK Peitsch Manuel C MC Kuczaj Arkadiusz A Vanscheeuwijck Patrick P Hoeng Julia J

Journal of applied toxicology : JAT 20210406 10

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 e ...[more]

PMID: 33825214

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Project description:The objective of this study was to compare the biological and toxicological response of apolipoprotein E-deficient (Apoe-/-) mice to 3R4F mainstream smoke exposure for 2 months in whole-body exposure chambers (WBEC) and nose-only exposure chambers (NOEC). Female ApoE-/- mice were randomized into four groups: two Sham groups, exposed to filtered air, and two 3R4F groups, exposed to CS from the 3R4F reference cigarette (550 Âµg TPM/L). Half the number of mice in the Sham- and CS-exposed groups were exposed in WBECs and the other half in NOECs. The exposure phase lasted 9 weeks and included 1 week of adaption, during which exposure in both chamber types was escalated in dose and duration to a maximum of 4 h per day. The TPM concentration and exposure duration in WBECs were matched to those in NOECs on the basis of the regimen that the mice tolerated, as determined by in-life findings on acute signs of nicotine toxicity. Fresh air breaks were introduced during the exposure period to maintain carboxyhemoglobin (COHb) concentrations at acceptable levels. More frequent and longer fresh air breaks were required for exposure in the WBEC than in the NOEC because of the greater internal volumeâ€”and, consequently, the longer durationâ€”required to clear smoke from the WBEC than from the NOEC. For animals in NOECs, a 30-min fresh air break was introduced after 2 and 3 h of exposure. For animals in WBECs, a 30-min fresh air break was introduced after 1 and 2 h of exposure and a 60-min fresh air break after the third hour of exposure. The general condition and health of the mice following exposure were monitored throughout the study. Full necropsy was performed 16-20 h after the last exposure without prior fasting, in accordance with previously described methods (Vanscheeuwijck et al., 2002). Differences between WBEC and NOEC expsoure were analyzed with regard to aerosol uptake, disease endpoints (adaptive changes in nasal epithelia, changes in lung function and inflammatory parameters, plasma cholesterol/triglyceride levels in lipoprotein fractions, and atherosclerosis plaque development), and systems biology endpoints (changes in the lung proteome and liver, nasal epithelial, and heart transcriptomes). All procedures involving animals were performed in a facility accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International and licensed by the Agri-Food & Veterinary Authority of Singapore, with approval from an Institutional Animal Care and Use Committee and in compliance with the National Advisory Committee for Laboratory Animal Research Guidelines on the Care and Use of Animals for Scientific Purposes (NACLAR, 2004). Here, the protein expression data for lung tissue assessed by iTRAQ®-based quantitative proteomics will be described.

Dataset Information

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.

Publications

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<sup>-/-</sup> mouse model.

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Dataset Information

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.

Publications

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<sup>-/-</sup> mouse model.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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.