The specific free radical scavenger edaravone suppresses fibrosis in the bleomycin-induced and tight skin mouse models of systemic sclerosis

Ayumi Yoshizaki, Koichi Yanaba, Asako Ogawa, Yohei Iwata, Fumihide Ogawa, Motoi Takenaka, Kazuhiro Shimizu, Yoshihide Asano, Takafumi Kadono, Shinichi Sato

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

Objective Patients with systemic sclerosis (SSc) exhibit enhanced production of free radicals due to ischemia and reperfusion injury following Raynaud's phenomenon, an initial clinical manifestation. Oxidative stress induces cytokine production, inflammatory cell recruitment, and tissue injury in several inflammatory diseases. The aim of this study was to examine the effect of edaravone, a free radical scavenger, on the development of fibrosis and autoimmunity in two different mouse models of SSc. Methods The bleomycin-induced SSc model in mice and the tight skin mouse model were used to evaluate the effect of edaravone on fibrosis and immunologic abnormalities. To assess the reaction of fibroblasts to stimulation with free radicals, fibroblasts from these mice were cultured with NONOate, a nitric oxide-releasing agent, and hydrogen peroxide. Results Treatment with edaravone reduced fibrosis in mice with bleomycin-induced SSc and in TSK/+ mice. The production of free radicals was also attenuated by edaravone in both models. In addition, production of fibrogenic cytokines such as interleukin-6 and transforming growth factor β1, production of anti-topoisomerase I antibody, and the degree of hypergammaglobulinemia were reduced by edaravone. Furthermore, bleomycin induced the production of H2O2 and nitric oxide from inflammatory cells, and collagen production was increased in fibroblasts cultured with H2O2 and NONOate. Conclusion This study is the first to show that edaravone has a significant inhibitory effect on fibrosis both in the bleomycin-induced SSc model and in TSK/+ mice. These results indicate that edaravone should be further evaluated for potential use as an antifibrotic agent in SSc.

Original languageEnglish
Pages (from-to)3086-3097
Number of pages12
JournalArthritis and Rheumatism
Volume63
Issue number10
DOIs
Publication statusPublished - 10-2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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