Carbocisteine protects against emphysema induced by cigarette smoke extract in rats.
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.
Hanaoka
Masayuki
M
First Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan. Electronic address: masayuki@shinshu-u.ac.jp.
Droma
Yunden
Y
First Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Chen
Yan
Y
First Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Agatsuma
Toshihiko
T
First Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Kitaguchi
Yoshiaki
Y
First Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Voelkel
Norbert F
NF
Victoria Johnson Center for Obstructive Lung Diseases, Virginia Commonwealth University, Richmond, VA.
Kubo
Keishi
K
First Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
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
D002233:Carbocysteine