Inhibitory effects of TRK-530 on rat adjuvant arthritis.
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.
Tanahashi
M
M
Basic Research Laboratories, Toray Industries, Inc., Kanagawa, Japan. tanahash@blab.toray.co.jp
Funaba
Y
Y
Itoh
M
M
Kawabe
N
N
Nakadate-Matsushita
T
T
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D001853:Bone Marrow / Q000473:pathology; D001842:Bone and Bones / Q000473:pathology; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D005528:Foot / Q000473:pathology; D006614:Hindlimb / Q000473:pathology; D007375:Interleukin-1 / Q000097:blood; D017737:Macrophages, Peritoneal / Q000187:drug effects; D019158:N-Acetylneuraminic Acid / Q000097:blood; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004164:Diphosphonates; D007375:Interleukin-1; C109548:TRK 530; D019158:N-Acetylneuraminic Acid