Carbon monoxide-bound hemoglobin-vesicles for the treatment of bleomycin-induced pulmonary fibrosis

Saori Nagao, Kazuaki Taguchi, Hiromi Sakai, Ryota Tanaka, Hirohisa Horinouchi, Hiroshi Watanabe, Koichi Kobayashi, Masaki Otagiri, Toru Maruyama

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Carbon monoxide (CO) has potent anti-inflammatory and anti-oxidant effects. We report herein on the preparation of a nanotechnology-based CO donor, CO-bound hemoglobin-vesicles (CO-HbV). We hypothesized that CO-HbV could have a therapeutic effect on idiopathic pulmonary fibrosis (IPF), an incurable lung fibrosis, that is thought to involve inflammation and the production of reactive oxygen species (ROS). Pulmonary fibril formation and respiratory function were quantitatively evaluated by measuring hydroxyproline levels and forced vital capacity, respectively, using a bleomycin-induced pulmonary fibrosis mice model. CO-HbV suppressed the progression of pulmonary fibril formation and improved respiratory function compared to saline and HbV. The suppressive effect of CO-HbV on pulmonary fibrosis can be attributed to a decrease in ROS generation by inflammatory cells, NADPH oxidase 4 and the production of inflammatory cells, cytokines and transforming growth factor-β in the lung. This is the first demonstration of the inhibitory effect of CO-HbV on the progression of pulmonary fibrosis via the anti-oxidative and anti-inflammatory effects of CO in the bleomycin-induced pulmonary fibrosis mice model. CO-HbV has the potential for use in the treatment of, not only IPF, but also a variety of other ROS and inflammation-related disorders.

Original languageEnglish
Pages (from-to)6553-6562
Number of pages10
JournalBiomaterials
Volume35
Issue number24
DOIs
Publication statusPublished - 2014 Aug
Externally publishedYes

Keywords

  • Antioxidant
  • Fibrosis
  • Inflammation
  • Liposome
  • Lung

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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  • Cite this

    Nagao, S., Taguchi, K., Sakai, H., Tanaka, R., Horinouchi, H., Watanabe, H., Kobayashi, K., Otagiri, M., & Maruyama, T. (2014). Carbon monoxide-bound hemoglobin-vesicles for the treatment of bleomycin-induced pulmonary fibrosis. Biomaterials, 35(24), 6553-6562. https://doi.org/10.1016/j.biomaterials.2014.04.049