Investigation of the anti-inflammatory properties of hydroxypyridinones.
Synovial iron deposition associated with rheumatoid disease may result in the production of highly reactive oxygen free radicals, leading to tissue damage. This chain of events can be interrupted by iron chelation. Families of strong iron (III) chelators have been tested for their iron scavenging properties in vitro and their effects assessed in vivo using a rat model of inflammation. All the chelators competed successfully for iron with apotransferrin, and some removed up to 34% of iron from ferritin. The best anti-inflammatory effects were achieved with the most hydrophilic chelators and those which chelated iron most avidly. Activity was dependent on dose. The route of administration was also an important factor with lower affinity chelators. This work introduces a range of simple bidentate iron chelators, which under certain conditions exceed desferrioxamine in their iron scavenging abilities, and some of which, in this simple animal model, approach indomethacin in their anti-inflammatory capabilities.
Hewitt
S D
SD
Cancer Research Unit, University of York, Heslington.
Hider
R C
RC
Sarpong
P
P
Morris
C J
CJ
Blake
D R
DR
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000378:metabolism / Q000627:therapeutic use*; D008958:Models, Molecular; D010998:Pleurisy / Q000188:drug therapy* / Q000378:metabolism; D011728:Pyridones / Q000378:metabolism / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007502:Iron Chelating Agents; D011728:Pyridones; D007501:Iron