title: Edaravone inhibits collagen-induced arthritis possibly through suppression of nuclear factor-kappa B.
abstract: OBJECTIVE
  Rheumatoid arthritis (RA) is a chronic autoimmune disease which is induced by proinflammatory cytokines or oxidative stress. The activation of nuclear factor-kappa B (NF-kappaB) that contributed to imbalance between apoptosis and proliferation of rheumatoid synovial cells (SC). Edaravone, clinically available free radical scavenger in Japan, is confirmed to be beneficial in the acute stage of stroke. We aimed to investigate the suppressive effect of edaravone on collagen-induced arthritis (CIA) mice and on the activated molecules in SC stimulated by interleukin-1beta (IL-1beta).
  
  
  METHODS
  Edaravone was administrated intravenously at a dose of 3mg/kg of body weight to CIA mice. The progression of CIA was evaluated by the macroscopic arthritis scoring system of paws. Interleukin-6 (IL-6) and matrix metalloproteinase-3 (MMP-3) concentrations in culture medium of human SC were measured by enzyme linked immunosorbent assays. Caspase-3/7 activity and nuclear factor-kappa B (NF-kappaB) protein level of cultured human SC were estimated by fluorometric assay and Western blot analysis, respectively.
  
  
  RESULTS
  Edaravone significantly decreased macroscopic arthritis score in CIA mice. Acceleration of IL-6 and MMP-3 productions and attenuation of caspase-3/7 activity in IL-1beta-stimulated SC were abated by edaravone. Activated NF-kappaB in IL-1beta-stimulated SC was suppressed by edaravone.
  
  
  CONCLUSIONS
  Edaravone, antioxidants available for clinical use, appears to have therapeutic effect on RA. We suggest that the inhibitory effect of edaravone on RA might be exerted, at least in part, through suppression of activated NF-kappaB. Therefore, we expect therapeutical use of edaravone as an anti-rheumatic agent.
authors.affiliation: Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, Kohasu, Okoh-Cho, Nankoku, Kochi 783-8505, Japan. ariik@kochi-u-ac.jp
authors.forename: Kaoru
authors.initials: K
authors.lastname: Arii
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Kumon
authors.forename: Kunio
authors.initials: K
authors.lastname: Sugahara
authors.forename: Ko
authors.initials: K
authors.lastname: Nakatani
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Tadashi
authors.initials: T
authors.lastname: Suehiro
authors.forename: Kozo
authors.initials: K
authors.lastname: Hashimoto
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000517:prevention & control*; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002478:Cells, Cultured; D000077553:Edaravone; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis; D051379:Mice; D013583:Synovial Membrane / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D051996:Transcription Factor RelA / Q000378:metabolism*
chemical_list: D015850:Interleukin-6; D051996:Transcription Factor RelA; D053148:Caspase 3; D053179:Caspase 7; D019278:Matrix Metalloproteinase 3; D000077553:Edaravone; D000983:Antipyrine