The action of nine chelators on iron-dependent radical damage.
Nine iron chelators were tested in five systems for their effects on radical-generation and conversion at chelator: iron molar ratios from 0.1 to 10. Stimulatory actions might distinguish toxic from safer chelators. Radical-generating reactions which represent different aspects of iron (ferrous and ferric) availability were studied: a) the reaction with hydrogen peroxide to hydroxylate benzoate; b) the oxidation of ascorbate; c) the reaction with hydrogen peroxide to fragment proteins; d) the reaction with hydrogen peroxide to permit amplified chemiluminescence; and e) the induction of peroxidation of mitochondrial membrane lipids. The compounds used were HBED, CP130, Desferal, EDTA, pyridine-hydrazone (CGP 43'902B), Ferrozine, CP94 (CGP 46'700), L1 (CGP 37,391) and rhodotorulic acid (CGP 45 274). Only the hexadentate compounds HBED, CP130 and Desferal were uniformly inhibitory ("protective"). The protective compounds were also apparently more stable during radical fluxes than the other chelators.
Dean
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Cell Biology Group, Heart Research Institute, Sydney NSW, Australia.
Nicholson
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D000818:Animals; D001205:Ascorbic Acid / Q000737:chemistry; D001565:Benzoates / Q000737:chemistry; D005609:Free Radicals; D006900:Hydroxylation; D007501:Iron / Q000633:toxicity; D007502:Iron Chelating Agents / Q000494:pharmacology; D007700:Kinetics; D008163:Luminescent Measurements; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013329:Structure-Activity Relationship; D013367:Submitochondrial Particles / Q000187:drug effects / Q000378:metabolism
D001565:Benzoates; D005609:Free Radicals; D007502:Iron Chelating Agents; D012710:Serum Albumin, Bovine; D007501:Iron; D001205:Ascorbic Acid