Inhibitory Effects of TRK-530 on Rat Adjuvant Arthritis

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Abstract
TRK-530 is a novel bisphosphonate derivative. We examined the anti-inflammatory effects of TRK-530 on adjuvant arthritis (AA) rats. When TRK-530 at a dose of 2.5 mg/kg was administered for 2 weeks to AA rats, it inhibited destructive changes in arthritic joints such as paw edema, bone loss and joint degeneration. TRK-530 also inhibited splenomegaly and suppressed the increase in serum sialic acid which is measured as a systemic parameter of inflammation. To clarify the inhibitory mechanism of TRK-530, interleukin-1 (IL-1)-like activities of resident peritoneal macrophages in AA rats given TRK-530 were compared with those of control rats. We found that TRK-530 inhibited IL-1-like activity induced by bacterial lipopolysaccharide 6 weeks after administration when the IL-1-like activities of control rats were still at high levels. These findings suggest that TRK-530 exerts anti-inflammatory activities in AA rats.

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