title: Therapeutic effect of lecithinized superoxide dismutase on pulmonary emphysema.
abstract: No medication exists that clearly improves the 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 because of an imbalance in proteases and antiproteases and increased apoptosis. Superoxide dismutase (SOD) catalyzes the dismutation of superoxide anions. Lecithinized human Cu/Zn- 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 leukocytes 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 proinflammatory 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 the 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.
authors.affiliation: Graduated School of Medical and Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Tanaka
authors.forename: Yuta
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Yuri
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Takushi
authors.initials: T
authors.lastname: Namba
authors.forename: Keizo
authors.initials: K
authors.lastname: Sato
authors.forename: Kazutetsu
authors.initials: K
authors.lastname: Aoshiba
authors.forename: Arata
authors.initials: A
authors.lastname: Azuma
authors.forename: Tohru
authors.initials: T
authors.lastname: Mizushima
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D054709:Lecithins / Q000737:chemistry* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D010447:Peptide Hydrolases / Q000378:metabolism; D010713:Phosphatidylcholines / Q000737:chemistry; D011014:Pneumonia / Q000188:drug therapy / Q000473:pathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy; D011656:Pulmonary Emphysema / Q000188:drug therapy*; D012129:Respiratory Function Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000737:chemistry* / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D000515:alpha 1-Antitrypsin / Q000378:metabolism
chemical_list: D018925:Chemokines; D016207:Cytokines; D054709:Lecithins; D010713:Phosphatidylcholines; D000515:alpha 1-Antitrypsin; D013481:Superoxides; D013482:Superoxide Dismutase; D010447:Peptide Hydrolases; D010196:Pancreatic Elastase