No medication exists that clearly improves mortality of chronic obstructive pulmonary disease (COPD). Oxidative molecules, in particular superoxide anions play important roles in the COPD-associated abnormal inflammatory response and pulmonary emphysema, which arises due to an imbalance in proteases and antiproteases and increased apoptosis. Superoxide dismutase (SOD) catalyses the dismutation of a superoxide anions. Lecithinized SOD (PC-SOD) has overcome a number of the clinical limitations of SOD, including low tissue affinity and low stability in plasma. In this study, we examine the effect of PC-SOD on elastase-induced pulmonary emphysema, an animal model of COPD. The severity of the pulmonary inflammatory response and emphysema in mice was assessed by various criteria, such as the number of leucocytes in the bronchoalveolar lavage fluid and the enlargement of airspace. Not only intravenous administration but also inhalation of PC-SOD suppressed elastase-induced pulmonary inflammation, emphysema and dysfunction. Inhalation of PC-SOD suppressed the elastase-induced increase in the pulmonary level of superoxide anions and apoptosis. Inhalation of PC-SOD also suppressed elastase-induced activation of proteases and decreased in the level of antiproteases and expression of pro-inflammatory cytokines and chemokines. We also found that inhalation of PC-SOD suppressed cigarette smoke-induced pulmonary inflammation. The results suggest that PC-SOD protects against pulmonary emphysema by decreasing the pulmonary level of superoxide anions, resulting in inhibition of inflammation and apoptosis and amelioration of the protease/antiprotease imbalance. We propose that inhalation of PC-SOD would be therapeutically beneficial for COPD.
- chronic obstructive pulmonary disease
- lecithinized superoxide dismutase
- pulmonary disease
- superoxide dismutase
- Received January 6, 2011.
- Revision received June 1, 2011.
- Accepted June 3, 2011.
- The American Society for Pharmacology and Experimental Therapeutics