title: Systemic effects of acute cigarette smoke exposure in mice.
abstract: BACKGROUND
  Cigarette smoke (CS) causes both pulmonary and extrapulmonary disorders.
  
  
  OBJECTIVE
  To determine the pulmonary and extrapulmonary effects of acute CS exposure in regard to inflammation, oxidative stress and DNA damage.
  
  
  METHODS
  Mice were exposed to CS for 10 days and then their lungs, heart, liver, pancreas, kidneys, gastrocnemius muscle and subcutaneous (inguinal and flank) and visceral (retroperitoneum and periuterus) adipose tissues were excised. Bronchoalveolar lavage fluid samples were obtained for differential cell analysis. Inflammatory cell infiltration of the tissues was assessed by immunohistochemistry for Mac-3(+) cells, F4/80(+) cells and CD45(+) cells. Oxidative stress was determined by immunohistochemistry for thymidine glycol (a marker of DNA peroxidation) and 4-hydroxy hexenal (a marker of lipid peroxidation), by enzyme-linked immunosorbent assay for protein carbonyls (a marker of protein peroxidation) and by measurements of enzyme activities of glutathione peroxidase, superoxide dismutase and catalase. DNA double-strand breaks were assessed by immunohistochemistry for γH2AX.
  
  
  RESULTS
  CS exposure-induced inflammatory cell infiltration, oxidative stress and DNA damage in the lung. Neither inflammatory cell infiltration nor DNA damage was observed in any extrapulmonary organs. However, oxidative stress was increased in the heart and inguinal adipose tissue.
  
  
  CONCLUSIONS
  Induction of inflammatory cell infiltration and DNA damage by acute CS exposure was confined to the lung. However, an increased oxidative burden occurred in the heart and some adipose tissue, as well as in the lung.
  
  
  CONCLUSIONS
  Although extrapulmonary effects of CS are relatively modest compared with the pulmonary effects, some extrapulmonary organs are vulnerable to CS-induced oxidative stress.
authors.affiliation: Department of Respiratory Medicine, Tokyo Medical University Ibaraki Medical Center , Ibaraki , Japan .
authors.forename: Masayuki
authors.initials: M
authors.lastname: Itoh
authors.forename: Takao
authors.initials: T
authors.lastname: Tsuji
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakamura
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Fuchikami
authors.forename: Maki
authors.initials: M
authors.lastname: Takahashi
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Morozumi
authors.forename: Kazutetsu
authors.initials: K
authors.lastname: Aoshiba
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D053903:DNA Breaks, Double-Stranded; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006657:Histones / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress; D012906:Smoke / Q000009:adverse effects*; D013482:Superoxide Dismutase / Q000378:metabolism; D014026:Nicotiana
chemical_list: D006657:Histones; D012906:Smoke; C475961:gamma-H2AX protein, mouse; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase
keywords: Chronic obstructive pulmonary disease; DNA damage; cigarette smoke; inflammation; oxidative stress; systemic effect