The chelation of nonheme iron within sickle erythrocytes by the hydroxypyridinone chelator CP094.
Nonheme, nonferritin iron has been detected in membrane preparations from sickle erythrocytes and has been suggested to catalyze free radical reactions in these cells contributing to the development of membrane oxidation. In this study the hydroxypyridinone iron chelator, CP094, currently being evaluated as a potentially therapeutic chelator, and desferrioxamine have been studied for their abilities to chelate the nonheme iron within intact sickle erythrocytes under physiological conditions. The results suggest that CP094 can enter sickle erythrocytes, chelate nonheme iron and suppress membrane lipid peroxidation within a timescale in which desferrioxamine does not enter the cells. Suppression of lipid peroxidation showed no protective effect in an in vitro system inducing the formation of irreversibly sickled cells.
Hartley
A
A
Department of Neurological Science, Royal Free Hospital School of Medicine, London, United Kingdom.
Rice-Evans
C
C
D000755:Anemia, Sickle Cell / Q000097:blood*; D004910:Erythrocyte Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D006418:Heme / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007501:Iron / Q000097:blood*; D007502:Iron Chelating Agents / Q000494:pharmacology*; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects; D011728:Pyridones / Q000494:pharmacology*; D012016:Reference Values
D007502:Iron Chelating Agents; D011728:Pyridones; C068543:1,2-diethyl-3-hydroxypyridin-4-one; D006418:Heme; D007501:Iron