Suppression of adjuvant arthritis of rats by a novel matrix metalloproteinase‐inhibitor

T Hamada, N Arima, M Shindo… - British journal of …, 2000 - Wiley Online Library
T Hamada, N Arima, M Shindo, K Sugama, Y Sasaguri
British journal of pharmacology, 2000Wiley Online Library
BAY 12‐9566 (4‐[4‐(chlorophenyl) phenyl]‐4‐oxo‐2S‐(phenylthiomethyl) butanoic acid) is
a newly developed, synthetic matrix metalloproteinase (MMP) inhibitor (MMPI) that
selectively inhibits MMP‐2, MMP‐3 and MMP‐9 isozymes. We study the effect of BAY 12‐
9566 on inflammation and cartilage destruction in adjuvant‐induced arthritis (AA) in rats.
Rats were injected with adjuvant and treated for 21 days with vehicle, Indomethacin or BAY
12‐9566. AA was assessed: by measuring arthritic index, paw volume, urinary pyridinoline …
  • BAY 12‐9566 (4‐[4‐(chlorophenyl)phenyl]‐4‐oxo‐2S‐(phenylthiomethyl) butanoic acid) is a newly developed, synthetic matrix metalloproteinase (MMP) inhibitor (MMPI) that selectively inhibits MMP‐2, MMP‐3 and MMP‐9 isozymes. We study the effect of BAY 12‐9566 on inflammation and cartilage destruction in adjuvant‐induced arthritis (AA) in rats.
  • Rats were injected with adjuvant and treated for 21 days with vehicle, Indomethacin or BAY 12‐9566. AA was assessed: by measuring arthritic index, paw volume, urinary pyridinoline (Pyr) and deoxypyridinoline (Dpyr); by examining joint inflammation; and by microscopic morphometry of articular cartilages.
  • Oral treatment of rats for 22 days with 50 mg kg−1 body weight/d BAY 12‐9566 showed decreased AA as determined by improvement in body weight gain (P<0.01), arthritic index (P<0.05) and swelling of paws contralateral to the adjuvant injection site (P<0.05). Neutrophil infiltration and collagen degradation were also significantly lower (P<0.01) in this treatment group. Cartilage destruction was successfully suppressed (P<0.01) in rats treated with either 50 mg kg−1 body weight/d BAY 12‐9566 or 1 mg kg−1 body weight/d Indomethacin.
  • These results indicate that BAY 12‐9566 successfully suppressed inflammation and cartilage destruction in rats with AA. Moreover, these results also suggested that MMP‐2, MMP‐3 and MMP‐9 are involved in arthritic diseases such as rheumatoid arthritis.
British Journal of Pharmacology (2000) 131, 1513–1520; doi:10.1038/sj.bjp.0703751
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