title: Characterization of biochemical, functional and structural changes in mice respiratory organs chronically exposed to cigarette smoke.
abstract: Female C57BL/6 mice were exposed to mainstream cigarette smoke at 600 μg WTPM/L, 4 h/day and 5 days/week for up to 52 weeks. At 26, 52 and 65 weeks (52 weeks of exposure plus 13 weeks of no exposure), lungs were assessed for inflammation, function, histopathology and morphometry. Structural changes were observed and accompanied by altered lung function at 26 and 52 weeks (e.g. increase of static compliance and hysteresis, and decrease of elastance). Lung morphometry quantified significant increase in airspace enlargement at 52 weeks. Chronic smoke exposure induced inflammation in respiratory organs, e.g. mixed inflammatory cell infiltrates, perivascular lymphocyte infiltrates and pigmented alveolar macrophages in the lungs. Minimal or mild alveolar emphysema was diagnosed in 70% by 26 weeks or 80% by 52 weeks. After 13 weeks of recovery, most biochemical, histopathological and morphometrical alterations were restored, while emphysema was observed to persist at 18% incidence by 65 weeks. In conclusion, the employed exposure conditions induced emphysematous changes in the lungs, accompanied by altered lung function and morphological/histopathological changes. Following the 13 weeks of no exposure, morphological changes persisted, although some functional/biochemical alterations regressed.
authors.affiliation: Product Science Division, R&D Group, Japan Tobacco Inc. , Kanagawa , Japan .
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsuji
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Fujimoto
authors.forename: Kyeonghee Monica
authors.initials: KM
authors.lastname: Lee
authors.forename: Roger
authors.initials: R
authors.lastname: Renne
authors.forename: Asuka
authors.initials: A
authors.lastname: Iwanaga
authors.forename: Chigusa
authors.initials: C
authors.lastname: Okubo
authors.forename: Saeko
authors.initials: S
authors.lastname: Onami
authors.forename: Ayako Koizumi
authors.initials: AK
authors.lastname: Nomura
authors.forename: Tomoki
authors.initials: T
authors.lastname: Nishino
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoshimura
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects / Q000473:pathology; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002263:Carboxyhemoglobin / Q000032:analysis; D002452:Cell Count; D002454:Cell Differentiation; D003367:Cotinine / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D004646:Emphysema / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008810:Mice, Inbred C57BL; D009538:Nicotine / Q000097:blood; D009929:Organ Size / Q000187:drug effects; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D000393:Air Pollutants; D016207:Cytokines; D014028:Tobacco Smoke Pollution; D009538:Nicotine; D002263:Carboxyhemoglobin; D007770:L-Lactate Dehydrogenase; D003367:Cotinine
keywords: Chronic obstructive pulmonary disease (COPD); cigarette smoke; partial reversibility; pulmonary inflammation; static compliance