The induction of an erosive arthropathy in the guinea pig with copper II bisglycinate and its treatment with antirheumatic drugs.
Single intra-articular injections of copper II bisglycinate [Cu(II)gly] (30-300 micrograms) into guinea-pig knee joints induce progressive joint degradation which first appears after about 2 weeks and peaks about 12 weeks after injection. The stable complex, copper II bishistidinate (300 micrograms) was without effect. The Cu(II)gly induced syndrome has features more in common with osteoarthritis than rheumatoid arthritis in that erosion occurs in the absence of persistent synovial inflammation. The possibility that the damage may be caused by Cu(II)gly inducing free radical formation within the joint, leading to a self-perpetuating chain reaction is discussed. D-Penicillamine and other drugs were tested for their effects on the histological changes induced 4 weeks after the intra-articular injections of 100 micrograms Cu(II)gly. Few significant effects were observed and these were restricted to D-penicillamine, which caused inconsistent protection, sodium aurothiomalate which protected at a dose causing weight loss and prednisolone which exacerbated joint damage. It is concluded that the variability of the control response will need to be reduced before the model can be used for routine drug evaluation but it may be of value in the study of chronic degradative joint disease.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001168:Arthritis / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D004195:Disease Models, Animal; D005998:Glycine / Q000008:administration & dosage; D006168:Guinea Pigs; D006639:Histidine / Q000008:administration & dosage; D007270:Injections, Intra-Articular; D007719:Knee Joint / Q000473:pathology; D008297:Male; D009942:Organometallic Compounds / Q000008:administration & dosage; D010003:Osteoarthritis / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D010396:Penicillamine / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D009942:Organometallic Compounds; C045576:copper bis(histidinate); D006639:Histidine; C018493:cupric glycinate; D010396:Penicillamine; D005998:Glycine