MISC

2011年10月

The Specific Free Radical Scavenger Edaravone Suppresses Fibrosis in the Bleomycin-Induced and Tight Skin Mouse Models of Systemic Sclerosis

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

63
10
開始ページ
3086
終了ページ
3097
記述言語
英語
掲載種別
DOI
10.1002/art.30470
出版者・発行元
WILEY-BLACKWELL

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 beta 1, 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.

Web of Science ® 被引用回数 : 20

リンク情報
DOI
https://doi.org/10.1002/art.30470
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/21618208
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000295293000030&DestApp=WOS_CPL

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