Effect of auranofin on plasma fibronectin, C reactive protein, and albumin levels in arthritic rats.
Auranofin, a member of a class of compounds with disease modifying activity, was given to arthritic rats to determine if it could reverse the abnormal plasma concentrations of fibronectin (Fn), C reactive protein (CRP), and albumin, which were unaffected by treatment with non-steroidal anti-inflammatory drugs (NSAIDs). When auranofin was orally administered for two weeks to adjuvant induced arthritic rats it significantly inhibited swelling of the injected and non-injected paws at doses of 3 and 10 mg/kg. Rocket electroimmunoassay measurement of plasma proteins in normal, arthritic, and auranofin treated arthritic rats indicated that auranofin at 10 mg/kg significantly decreased (by 77%) the abnormally high concentration of arthritic rat plasma Fn, though it had no effect on Fn concentrations when administered to normal rats. CRP, which was raised approximately twofold above normal in arthritic rats, was reduced by 56% after treatment of arthritic rats with auranofin at 10 mg/kg, though CRP concentrations in normal rats were unaffected by auranofin treatment. Depressed albumin concentrations in arthritic rats were significantly enhanced (by 30%) by dosing with 10 mg/kg of auranofin. At the 3 mg/kg dose, auranofin did not significantly change plasma concentrations of Fn, CRP, and albumin in arthritic rats. At a dose of 10 mg/kg, however, auranofin, in addition to inhibiting chronic systemic paw inflammation, also altered abnormal concentrations of plasma Fn, CRP, and albumin in the adjuvant arthritic rat, thus distinguishing auranofin from standard NSAIDs we have previously tested.
Connolly
K M
KM
Department of Chemotherapy, Glaxo Research Division, Research Triangle Park, North Carolina 27709.
Stecher
V J
VJ
Pruden
D J
DJ
D000818:Animals; D001168:Arthritis / Q000097:blood*; D001169:Arthritis, Experimental / Q000097:blood* / Q000188:drug therapy; D001310:Auranofin / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000032:analysis*; D005353:Fibronectins / Q000097:blood*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D012709:Serum Albumin / Q000032:analysis*
D005353:Fibronectins; D012709:Serum Albumin; D001310:Auranofin; D002097:C-Reactive Protein