Mechanism of exacerbation of rheumatoid synovitis by total-dose iron-dextran infusion: in-vivo demonstration of iron-promoted oxidant stress.
The mechanism by which a synovial flare occurred in a patient with rheumatoid arthritis after intravenous infusion of iron-dextran was investigated. After the infusion, serum and synovial-fluid iron-binding capacity became saturated, giving rise to low-molecular-mass iron chelates with the capacity to cause oxidative damage ("bleomycin-iron"). At the same time lipid peroxidation and the concentration of oxidised ascorbic acid (dehydroascorbate) increased in both serum and synovial fluid, and red-cell glutathione fell. These changes corresponded closely to an exacerbation of rheumatoid synovitis. Hepatic function was transiently disturbed 7 days after the infusion, reflecting hepatic oxidant stress within the iron-loaded liver. Such changes provide clear evidence that iron-catalysed oxidative reactions influence the inflammatory process in human beings.
D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D001761:Bleomycin; D005260:Female; D005978:Glutathione / Q000097:blood; D006801:Humans; D007262:Infusions, Intravenous; D007501:Iron / Q000378:metabolism*; D007505:Iron-Dextran Complex / Q000008:administration & dosage / Q000009:adverse effects*; D007719:Knee Joint / Q000503:physiopathology; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008875:Middle Aged; D013585:Synovitis / Q000378:metabolism*
D008054:Lipid Peroxides; D001761:Bleomycin; D007505:Iron-Dextran Complex; D007501:Iron; D005978:Glutathione