Redox cycling and lipid peroxidation: the central role of iron chelates.
Toxicities associated with redox cycling, including lipid peroxidation, are often attributed to the hydroxyl radical through a superoxide-driven, iron-catalyzed Haber-Weiss reaction. However, other cellular reducing agents more prevalent than superoxide, i.e., glutathione, ascorbate, cysteine and certain enzymes, can also reduce chelated iron and thereby initiate lipid peroxidation which is not inhibited by superoxide dismutase. The autoxidation of ferrous chelates yields partially reduced oxygen intermediates similar to those produced during the iron-catalyzed Haber-Weiss reaction. The mechanism of their formation, and the nature of the strong oxidant responsible for the initiation of lipid peroxidation are poorly understood, but are apparently influenced by the chelation of the iron. These conclusions stem from experiments which demonstrated variable amounts of inhibition of lipid peroxidation, dependent on the autoxidation of various ferrous chelates, by added superoxide dismutase or catalase. In addition, certain ferrous chelates are unable to initiate peroxidation of lipids in a liposomal configuration, yet capable of initiating peroxidation of lipids which were dispersed with a detergent. The results of these studies point out the need to isolate and identify the predominant physiological iron chelates for assessment of their ability to participate in redox related toxicities within the cell.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002951:Citrates / Q000494:pharmacology; D019343:Citric Acid; D004492:Edetic Acid / Q000494:pharmacology; D004798:Enzymes / Q000097:blood; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D007502:Iron Chelating Agents / Q000378:metabolism*; D050356:Lipid Metabolism; D008054:Lipid Peroxides / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats
D002951:Citrates; D004798:Enzymes; D007502:Iron Chelating Agents; D008054:Lipid Peroxides; D019343:Citric Acid; D000244:Adenosine Diphosphate; D004492:Edetic Acid; D005978:Glutathione