title: Effects of lecithinized superoxide dismutase and/or pirfenidone against bleomycin-induced pulmonary fibrosis.
abstract: BACKGROUND
  Idiopathic pulmonary fibrosis (IPF) involves lung injury induced by reactive oxygen species (ROS), such as superoxide anion, and fibrosis. Superoxide dismutase (SOD) catalyses the dismutation of superoxide anion to hydrogen peroxide. We recently reported that inhalation of lecithinized SOD (PC-SOD) ameliorated bleomycin-induced pulmonary fibrosis. We here studied effects of PC-SOD on bleomycin-induced pulmonary fibrosis and lung dysfunction and compared the results to those obtained with pirfenidone, a newly developed drug for IPF.
  
  
  METHODS
  Lung mechanics (elastance) and respiratory function (FVC) were assessed using a computer-controlled ventilator. Respiratory function was evaluated by monitoring percutaneous arterial oxygen saturation (SpO2).
  
  
  RESULTS
  Both inhalation of PC-SOD and oral administration of pirfenidone ameliorated bleomycin-induced pulmonary fibrosis and changes in lung mechanics. Administration of bleomycin produced a decrease in both FVC and SpO2. PC-SOD treatment led to significant recovery of both parameters, whereas pirfenidone improved only SpO2. PC-SOD suppressed the bleomycin-induced pulmonary inflammatory response and production of superoxide anions in the lung more effectively than pirfenidone. Furthermore, both PC-SOD and pirfenidone produced a therapeutic effect even when the drug was administered after the development of fibrosis. PC-SOD and pirfenidone also produced a synergistic therapeutic effect.
  
  
  CONCLUSIONS
  These results suggest that the superior activity of PC-SOD to pirfenidone against bleomycin-induced pulmonary fibrosis and lung dysfunction is due to its unique antioxidant activity. We propose that treatment of IPF with a combination of PC-SOD and pirfenidone could be therapeutically beneficial.
authors.affiliation: Department of Analytical Chemistry, Faculty of Pharmacy, Keio University, Tokyo; Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto.
authors.forename: Ken-Ichiro
authors.initials: KI
authors.lastname: Tanaka
authors.affiliation: Department of Internal Medicine, Division of Respiratory, Infection, and Oncology, Nippon Medical School, Tokyo, Japan.
authors.forename: Arata
authors.initials: A
authors.lastname: Azuma
authors.affiliation: Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Miyazaki
authors.affiliation: Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto.
authors.forename: Keizo
authors.initials: K
authors.lastname: Sato
authors.affiliation: Department of Analytical Chemistry, Faculty of Pharmacy, Keio University, Tokyo; Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto. Electronic address: mizushima-th@pha.keio.ac.jp.
authors.forename: Tohru
authors.initials: T
authors.lastname: Mizushima
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use; D001761:Bleomycin / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000627:therapeutic use; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D010713:Phosphatidylcholines / Q000008:administration & dosage*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D011728:Pyridones / Q000008:administration & dosage* / Q000627:therapeutic use; D013482:Superoxide Dismutase / Q000008:administration & dosage*; D016896:Treatment Outcome; D014797:Vital Capacity / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016166:Free Radical Scavengers; D010713:Phosphatidylcholines; D011728:Pyridones; D001761:Bleomycin; C093844:pirfenidone; D013482:Superoxide Dismutase; C434045:lecithinized superoxide dismutase