Effect of novel 1-alkyl-3-hydroxy-2-methylpyrid-4-one chelators on uptake and release of iron from macrophages.
The effect of several iron chelators on iron uptake and release by mouse peritoneal macrophages has been investigated. The 1,2-dimethyl (L1) and 1-ethyl-2-methyl (L1NEt) derivatives of 3-hydroxypyrid-4-one markedly enhanced iron mobilisation from macrophages pulsed with 59Fe-transferrin-antitransferrin immune complexes and were more effective than desferrioxamine, maltol, or mimosine. Release increased with increasing chelator concentration. None of the chelators donated significant amounts of iron to macrophages, and none showed any cytotoxic effect. The synthetic alpha-ketohydroxypyridine chelators may therefore be active in removing iron from the reticuloendothelial system as well as from hepatocytes, and indeed may be superior to desferrioxamine.
Brock
J H
JH
University Department of Bacteriology and Immunology, Western Infirmary, Glasgow, Scotland.
Licéaga
J
J
Arthur
H M
HM
Kontoghiorghes
G J
GJ
D000818:Animals; D000077543:Deferiprone; D003676:Deferoxamine / Q000494:pharmacology; D007501:Iron / Q000378:metabolism* / Q000493:pharmacokinetics; D007502:Iron Chelating Agents / Q000494:pharmacology*; D007504:Iron Radioisotopes; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008898:Mimosine / Q000494:pharmacology; D011728:Pyridones / Q000494:pharmacology*; D011753:Pyrones / Q000494:pharmacology
D007502:Iron Chelating Agents; D007504:Iron Radioisotopes; D011728:Pyridones; D011753:Pyrones; D000077543:Deferiprone; C048630:1-ethyl-2-methyl-3-hydroxypyridin-4-one; C008316:maltol; D008898:Mimosine; D007501:Iron; D003676:Deferoxamine