title: The specific free radical scavenger edaravone suppresses fibrosis in the bleomycin-induced and tight skin mouse models of systemic sclerosis.
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.
  
  
  CONCLUSIONS
  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.
authors: Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors: Ayumi
authors: A
authors: Yoshizaki
authors: Koichi
authors: K
authors: Yanaba
authors: Asako
authors: A
authors: Ogawa
authors: Yohei
authors: Y
authors: Iwata
authors: Fumihide
authors: F
authors: Ogawa
authors: Motoi
authors: M
authors: Takenaka
authors: Kazuhiro
authors: K
authors: Shimizu
authors: Yoshihide
authors: Y
authors: Asano
authors: Takafumi
authors: T
authors: Kadono
authors: Shinichi
authors: S
authors: Sato