Therapeutic effect of lecithinized superoxide dismutase on bleomycin-induced pulmonary fibrosis

Ken Ichiro Tanaka, Tomoaki Ishihara, Arata Azuma, Shoji Kudoh, Masahito Ebina, Toshihiro Nukiwa, Yukihiko Sugiyama, Yuichi Tasaka, Takushi Namba, Tsutomu Ishihara, Keizo Sato, Yutaka Mizushima, Tohru Mizushima

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53 Citations (Scopus)

Abstract

Idiopathic pulmonary fibrosis (IPF) is thought to involve inflammatory infiltration of leukocytes, lung injury induced by reactive oxygen species (ROS), in particular superoxide anion, and fibrosis (collagen deposition). No treatment has been shown to improve definitively the prognosis for IPF patients. Superoxide dismutase (SOD) catalyzes the dismutation of superoxide anion to hydrogen peroxide, which is subsequently detoxified by catalase. Lecithinized SOD (PC-SOD) has overcome clinical limitations of SOD, including low tissue affinity and low stability in plasma. In this study, we examined the effect of PC-SOD on bleomycin-induced pulmonary fibrosis. Severity of the bleomycin-induced fibrosis in mice was assessed by various methods, including determination of hydroxyproline levels in lung tissue. Intravenous administration of PC-SOD suppressed the bleomycin-induced increase in the number of leukocytes in bronchoalveolar lavage fluid. Bleomycin-induced collagen deposition and increased hydroxyproline levels in the lung were also suppressed in animals treated with PC-SOD, suggesting that PC-SOD suppresses bleomycininduced pulmonary fibrosis. The dose-response profile of PC-SOD was bell-shaped, but concurrent administration of catalase restored the ameliorative effect at high doses of PC-SOD. Intratracheal administration or inhalation of PC-SOD also attenuated the bleomycininduced inflammatory response and fibrosis. The bell-shaped doseresponse profile of PC-SOD was not observed for these routes of administration. We consider that, compared with intravenous administration, inhalation of PC-SOD may be a more therapeutically beneficial route of administration due to the higher safety and quality of life of the patient treated with this drug.

Original languageEnglish
Pages (from-to)L348-L360
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume298
Issue number3
DOIs
Publication statusPublished - 2010 Mar

Keywords

  • Idiopathic pulmonary fibrosis
  • Reactive oxygen species

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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    Tanaka, K. I., Ishihara, T., Azuma, A., Kudoh, S., Ebina, M., Nukiwa, T., Sugiyama, Y., Tasaka, Y., Namba, T., Ishihara, T., Sato, K., Mizushima, Y., & Mizushima, T. (2010). Therapeutic effect of lecithinized superoxide dismutase on bleomycin-induced pulmonary fibrosis. American Journal of Physiology - Lung Cellular and Molecular Physiology, 298(3), L348-L360. https://doi.org/10.1152/ajplung.00289.2009