Effects of lecithinized superoxide dismutase and/or pirfenidone against bleomycin-induced pulmonary fibrosis

Ken Ichiro Tanaka, Arata Azuma, Yuri Miyazaki, Keizo Sato, Tohru Mizushima

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)

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 (SpO 2). 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.

Original languageEnglish
Pages (from-to)1011-1019
Number of pages9
JournalChest
Volume142
Issue number4
DOIs
Publication statusPublished - 2012 Oct

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

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