Stimulation and inhibition of iron-dependent lipid peroxidation by desferrioxamine.
Peroxidation of rat brain synaptosomes was assessed by the formation of thiobarbituric acid reactive products in either 50 mM potassium phosphate buffer (pH 7.4) or pH adjusted saline. In phosphate, addition of Fe2+ resulted in a dose-related increase in lipid peroxidation. In saline, stimulation of lipid peroxidation by Fe2+ was maximal at 30 uM, and was less at concentrations of 100 uM and above. Whereas desferrioxamine caused a dose-related inhibition of iron-dependent lipid peroxidation in phosphate, it stimulated lipid peroxidation with Fe2+ by as much as 7-fold in saline. The effects of desferrioxamine depended upon the oxidation state of iron, and the concentration of desferrioxamine and lipid. The results suggest that lipid and desferrioxamine compete for available iron. The data are consistent with the hypothesis that either phosphate or desferrioxamine may stimulate iron-dependent lipid peroxidation under certain circumstances by favoring formation of Fe2+/Fe3+ ratios.
Braughler
J M
JM
CNS Diseases Research Unit, Upjohn Company, Kalamazoo, MI 49001.
Chase
R L
RL
Pregenzer
J F
JF
D000818:Animals; D001921:Brain / Q000166:cytology; D003676:Deferoxamine / Q000494:pharmacology*; D007501:Iron / Q000378:metabolism*; D008054:Lipid Peroxides / Q000378:metabolism*; D008823:Micelles; D051381:Rats; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013858:Thiobarbiturates
D008054:Lipid Peroxides; D008823:Micelles; D013858:Thiobarbiturates; D007501:Iron; D003676:Deferoxamine; C029684:thiobarbituric acid