title: Carbocisteine protects against emphysema induced by cigarette smoke extract in rats.
abstract: BACKGROUND
  Chronic inflammation, imbalance of proteolytic and antiproteolytic activities, oxidative stress, and apoptosis of lung structural cells contribute to the pathogenesis of COPD. There is increasing evidence that carboxymethylcysteine (also known as carbocisteine) (CMC), which is commonly used for its mucoactive property, has diverse pharmacologic actions, including significant antioxidant activity. We hypothesize that CMC protects against cigarette smoke extract (CSE)-induced emphysema in rats via its antioxidant action.
  
  
  METHODS
  Sprague-Dawley rats were divided into four groups (n = 6 in each group): control group, CSE group, CSE + 125 mg/kg/d of CMC group, and CSE + 250 mg/kg/d of CMC group. The CSE was injected intraperitoneally once a week for 3 weeks, and CMC was administered daily via a gastric gavage for the same duration. Antioxidant activity in the pulmonary and serum levels, apoptotic index, caspase-3 activity, and matrix metalloproteinase (MMP)-2 and MMP-9 activities in lung tissues were measured.
  
  
  RESULTS
  CMC significantly protected against alveolar enlargement and parenchymal destruction in rats injected with CSE, resulting in prevention of the development of CSE-induced emphysema in the rats. CMC significantly protected the antioxidant activity in both the pulmonary and systemic levels, reduced pathologic apoptosis, and inhibited MMP-2 and MMP-9 activities in the lungs of rats with CSE-induced emphysema.
  
  
  CONCLUSIONS
  CMC protected against the development of CSE-induced emphysema in rats. The molecular mechanisms that were involved with stabilizing the biologic antioxidant activity resulted from the administration of CMC, which was connected to the inhibition of apoptosis and the reversal of the imbalance of proteolytic and antiproteolytic enzyme activities, eventually achieving the protection of the alveolar architecture of rats with emphysema.
authors.affiliation: First Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan. Electronic address: masayuki@shinshu-u.ac.jp.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hanaoka
authors.affiliation: First Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Yunden
authors.initials: Y
authors.lastname: Droma
authors.affiliation: First Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: First Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Agatsuma
authors.affiliation: First Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kitaguchi
authors.affiliation: Victoria Johnson Center for Obstructive Lung Diseases, Virginia Commonwealth University, Richmond, VA.
authors.forename: Norbert F
authors.initials: NF
authors.lastname: Voelkel
authors.affiliation: First Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Keishi
authors.initials: K
authors.lastname: Kubo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002233:Carbocysteine / Q000494:pharmacology / Q000627:therapeutic use*; D008168:Lung / Q000187:drug effects; D008297:Male; D011656:Pulmonary Emphysema / Q000209:etiology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012907:Smoking / Q000009:adverse effects
chemical_list: D002233:Carbocysteine