PMID- 17629561
OWN - NLM
STAT- MEDLINE
DCOM- 20071126
LR  - 20181201
IS  - 0161-5890 (Print)
IS  - 0161-5890 (Linking)
VI  - 45
IP  - 2
DP  - 2008 Jan
TI  - Edaravone inhibits collagen-induced arthritis possibly through suppression of 
      nuclear factor-kappa B.
PG  - 463-9
AB  - 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. CONCLUSION: 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.
FAU - Arii, Kaoru
AU  - Arii K
AD  - Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, 
      Kochi University, Kohasu, Okoh-Cho, Nankoku, Kochi 783-8505, Japan. 
      ariik@kochi-u-ac.jp
FAU - Kumon, Yoshitaka
AU  - Kumon Y
FAU - Sugahara, Kunio
AU  - Sugahara K
FAU - Nakatani, Ko
AU  - Nakatani K
FAU - Ikeda, Yukio
AU  - Ikeda Y
FAU - Suehiro, Tadashi
AU  - Suehiro T
FAU - Hashimoto, Kozo
AU  - Hashimoto K
LA  - eng
PT  - Journal Article
DEP - 20070716
PL  - England
TA  - Mol Immunol
JT  - Molecular immunology
JID - 7905289
RN  - 0 (Interleukin-6)
RN  - 0 (Transcription Factor RelA)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 7)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - S798V6YJRP (Edaravone)
RN  - T3CHA1B51H (Antipyrine)
SB  - IM
MH  - Animals
MH  - Antipyrine/*analogs & derivatives/pharmacology
MH  - Arthritis, Experimental/*prevention & control
MH  - Caspase 3/metabolism
MH  - Caspase 7/metabolism
MH  - Cells, Cultured
MH  - Edaravone
MH  - Female
MH  - Humans
MH  - Interleukin-6/biosynthesis
MH  - Male
MH  - Matrix Metalloproteinase 3/biosynthesis
MH  - Mice
MH  - Synovial Membrane/drug effects/enzymology/pathology
MH  - Transcription Factor RelA/*metabolism
EDAT- 2007/07/17 09:00
MHDA- 2007/12/06 09:00
CRDT- 2007/07/17 09:00
PHST- 2007/03/02 00:00 [received]
PHST- 2007/05/21 00:00 [revised]
PHST- 2007/05/22 00:00 [accepted]
PHST- 2007/07/17 09:00 [pubmed]
PHST- 2007/12/06 09:00 [medline]
PHST- 2007/07/17 09:00 [entrez]
AID - S0161-5890(07)00246-5 [pii]
AID - 10.1016/j.molimm.2007.05.020 [doi]
PST - ppublish
SO  - Mol Immunol. 2008 Jan;45(2):463-9. doi: 10.1016/j.molimm.2007.05.020. Epub 2007 
      Jul 16.