title: Effects of deferrioxamine on iron-catalyzed lipid peroxidation.
abstract: The kinetics of iron binding by deferrioxamine B mesylate and the ramifications of this process upon iron-catalyzed lipid peroxidation were assessed. The relative rates of Fe(III) binding by deferrioxamine varied for the chelators tested as follows: ADP greater than AMP greater than citrate greater than histidine greater than EDTA. The addition of a fivefold molar excess of deferrioxamine to that of Fe(III) did not result in complete binding (within 10 min) for any of the Fe(III) chelates tested except ADP:Fe(III). The rates of Fe(III) binding by deferrioxamine were greater at lower pH and when the competing chelator concentration was high in relationship to iron. The relatively slow binding of Fe(III) by deferrioxamine also affected lipid peroxidation, an iron-dependent process. The addition of deferrioxamine to an ascorbate- and ADP:Fe(III)-dependent lipid peroxidation system resulted in a time-dependent inhibition or stimulation of malondialdehyde formation (i.e., lipid peroxidation), depending on the ratio of deferrioxamine to iron. Converse to Fe(III), the rates of Fe(II) binding by deferrioxamine from the chelators tested above were rapid and complete (within 1 min), and resulted in the oxidation of Fe(II) to Fe(III). Lipid peroxidation dependent on Fe(II) autoxidation was stimulated by the addition of deferrioxamine. Malondialdehyde formation in this system was inhibited by the addition of catalase, and a similar extent of lipid peroxidation was achieved by substituting hydrogen peroxide for deferrioxamine. Collectively, these results suggest that the kinetics of Fe(III) binding by deferrioxamine is a slow, variable process, whereas Fe(II) binding is considerably faster. The binding of either valence of iron by deferrioxamine may result in variable effects on iron-catalyzed processes, such as lipid peroxidation, either via slow binding of Fe(III) or the rapid binding of Fe(II) with concomitant Fe(II) oxidation.
authors.affiliation: Biotechnology Center, Utah State University, Logan 84322-4705.
authors.forename: D M
authors.initials: DM
authors.lastname: Miller
authors.forename: N H
authors.initials: NH
authors.lastname: Spear
authors.forename: S D
authors.initials: SD
authors.lastname: Aust
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism; D002384:Catalysis; D003676:Deferoxamine / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000378:metabolism; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects*; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D007502:Iron Chelating Agents; D007501:Iron; D002374:Catalase; D013482:Superoxide Dismutase; D003676:Deferoxamine