Edaravone inhibits collagen-induced arthritis possibly through suppression of nuclear factor-kappa B.
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.
Arii
Kaoru
K
Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, Kohasu, Okoh-Cho, Nankoku, Kochi 783-8505, Japan. ariik@kochi-u-ac.jp
Kumon
Yoshitaka
Y
Sugahara
Kunio
K
Nakatani
Ko
K
Ikeda
Yukio
Y
Suehiro
Tadashi
T
Hashimoto
Kozo
K
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*
D015850:Interleukin-6; D051996:Transcription Factor RelA; D053148:Caspase 3; D053179:Caspase 7; D019278:Matrix Metalloproteinase 3; D000077553:Edaravone; D000983:Antipyrine