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Original Research: COPD |

Carbocisteine Protects Against Emphysema Induced by Cigarette Smoke Extract in Rats

Masayuki Hanaoka, MD, PhD; Yunden Droma, MD, PhD; Yan Chen, MD; Toshihiko Agatsuma, MD; Yoshiaki Kitaguchi, MD; Norbert F. Voelkel, MD; Keishi Kubo, MD, PhD, FCCP
Author and Funding Information

From the First Department of Medicine (Drs Hanaoka, Droma, Chen, Agatsuma, Kitaguchi, and Kubo), Shinshu University School of Medicine, Matsumoto, Japan; and the Victoria Johnson Center for Obstructive Lung Diseases (Dr Voelkel), Virginia Commonwealth University, Richmond, VA.

Correspondence to: Masayuki Hanaoka, MD, PhD, First Department of Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan; e-mail: masayuki@shinshu-u.ac.jp


Funding/Support: This work was partly supported by a grant to the Respiratory Failure Research Group from the Ministry of Health, Labour and Welfare, Japan.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2011 American College of Chest Physicians


Chest. 2011;139(5):1101-1108. doi:10.1378/chest.10-0920
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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.

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