Effects of prolonged administration of D-penicillamine or captopril in various strains of rats. Brown Norway rats treated with D-penicillamine develop autoantibodies, circulating immune complexes, and disseminated intravascular coagulation.
D-Penicillamine and captopril, two drugs that induce autoimmune manifestations in man, were administered orally for 5 to 10 months to various strains of rats. Three to eight weeks after D-penicillamine administration in a dosage of 20 to 50 mg per day, 73% of Brown Norway (BN) rats became ill. The disease was characterized by weight loss, dermatitis, and a high mortality presumably caused by disseminated intravascular coagulation. Microscopy revealed widespread granulomatous and necrotic lesions. The plasma of these animals contained antinuclear antibodies and immune complexes. In the kidney deposits of IgG were found in a linear pattern along the glomerular basement membrane. IgG eluted from diseased kidneys bound both "in vitro" and "in vivo" to kidney basement membranes. BN rats initially receiving 5 mg of D-penicillamine per day and subsequently 20 and 50 mg per day did not develop disease. No adverse effects were noted in Lewis (LEW) and Sprague-Dawley (SD) rats treated with 20 or 50 mg of D-penicillamine per day, nor in BN and LEW rats treated with 20 mg of captopril per day.
D000818:Animals; D000974:Antibodies, Antinuclear / Q000032:analysis; D000936:Antigen-Antibody Complex / Q000032:analysis; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D001485:Basement Membrane / Q000276:immunology / Q000648:ultrastructure; D002216:Captopril / Q000633:toxicity*; D004211:Disseminated Intravascular Coagulation / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D005260:Female; D007074:Immunoglobulin G / Q000032:analysis; D007678:Kidney Glomerulus / Q000276:immunology / Q000648:ultrastructure; D008297:Male; D010396:Penicillamine / Q000633:toxicity*; D011392:Proline / Q000031:analogs & derivatives*; D011650:Pulmonary Alveoli / Q000276:immunology / Q000648:ultrastructure; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains
D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D007074:Immunoglobulin G; D011392:Proline; D002216:Captopril; D010396:Penicillamine