The control of iron-induced oxidative damage in isolated rat-liver mitochondria by respiration state and ascorbate.
The reaction of iron (II) with H2O2 is believed to generate highly reactive species (e.g. .OH) capable of initiating biological damage. This study investigates the possibility that the severity of oxidative damage induced by iron in hepatic mitochondria is determined by the level of mitochondrial-H2O2 generation, which is believed to be particularly prominent in state-4 respiration. Iron-induced damage is found to be greater in state-4 than in state-3 respiration. Experiments using uncoupling agents and Ca++ to mimic state-3 conditions indicate that this effect reflects differences in the steady-state oxidation-level of the electron carriers of the respiratory chain (and hence the level of H2O2-generation), rather than changes in redox potential or transportation of the metal-ion. Evidence is also presented for a mechanism in which Fe(II) and H2O2 react inside the mitochondrial matrix. Ascorbate (vitamin C) is shown to be pro-oxidant in this system, except when present at very high concentration when it becomes antioxidant in nature.
Burkitt
M J
MJ
Department of Chemistry, University of York, Heslington, UK.
Gilbert
B C
BC
D000227:Adenine Nucleotides / Q000494:pharmacology; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005033:Ethylmaleimide / Q000494:pharmacology; D066298:In Vitro Techniques; D007501:Iron / Q000633:toxicity*; D008054:Lipid Peroxides / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects*; D010084:Oxidation-Reduction; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism; D013858:Thiobarbiturates; D013997:Time Factors; D014475:Uncoupling Agents / Q000494:pharmacology
D000227:Adenine Nucleotides; D008054:Lipid Peroxides; D013858:Thiobarbiturates; D014475:Uncoupling Agents; D007501:Iron; D002374:Catalase; D013482:Superoxide Dismutase; C029684:thiobarbituric acid; D005033:Ethylmaleimide; D001205:Ascorbic Acid; D002118:Calcium