title: Superiority of PC-SOD to other anti-COPD drugs for elastase-induced emphysema and alteration in lung mechanics and respiratory function in mice.
abstract: Bronchodilators (such as ipratropium bromide), steroids (such as fluticasone propionate), and newly developed anti-inflammatory drugs (such as roflumilast) are used for patients with chronic obstructive pulmonary disease (COPD). We recently reported that lecithinized superoxide dismutase (PC-SOD) confers a protective effect in mouse models of COPD. We here examined the therapeutic effect of the combined administration of PC-SOD with ipratropium bromide on pulmonary emphysema and compared the effect of PC-SOD to other types of drugs. The severity of emphysema in mice was assessed by various criteria. Lung mechanics (elastance) and respiratory function (ratio of forced expiratory volume in the first 0.05 s to forced vital capacity) were assessed. Administration of PC-SOD by inhalation suppressed elastase-induced pulmonary emphysema, alteration of lung mechanics, and respiratory dysfunction. The concomitant intratracheal administration of ipratropium bromide did not alter the ameliorating effects of PC-SOD. Administration of ipratropium bromide, fluticasone propionate, or roflumilast alone did not suppress the elastase-induced increase in the pulmonary level of superoxide anion, pulmonary inflammatory response, pulmonary emphysema, alteration of lung mechanics, or respiratory dysfunction as effectively as did PC-SOD. PC-SOD, but not the other drugs, showed a therapeutic effect even when the drug was administered after the development of emphysema. PC-SOD also suppressed the cigarette smoke-induced pulmonary inflammatory response and increase in airway resistance. Based on these results, we consider that the inhalation of PC-SOD would be therapeutically beneficial for COPD.
authors.affiliation: Dept. of Analytical Chemistry, Faculty of Pharmacy, Keio Univ., 1-5-30, Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Tanaka
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: D000280:Administration, Inhalation; D000403:Airway Resistance / Q000187:drug effects; D000631:Aminopyridines / Q000494:pharmacology / Q000627:therapeutic use; D000730:Androstadienes / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001549:Benzamides / Q000494:pharmacology / Q000627:therapeutic use; D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D003521:Cyclopropanes / Q000494:pharmacology / Q000627:therapeutic use; D000068298:Fluticasone; D005541:Forced Expiratory Volume; D009241:Ipratropium / Q000494:pharmacology / Q000627:therapeutic use; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D010196:Pancreatic Elastase; D010713:Phosphatidylcholines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D012143:Respiratory Physiological Phenomena / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D013481:Superoxides / Q000032:analysis; D014797:Vital Capacity
chemical_list: D000631:Aminopyridines; D000730:Androstadienes; D001549:Benzamides; D001993:Bronchodilator Agents; D003521:Cyclopropanes; D010713:Phosphatidylcholines; C424423:Roflumilast; D013481:Superoxides; D000068298:Fluticasone; D013482:Superoxide Dismutase; C434045:lecithinized superoxide dismutase; D010196:Pancreatic Elastase; D009241:Ipratropium