title: Iron-induced peroxidative injury to isolated rat hepatic mitochondria.
abstract: Peroxidative injury to the mitochondrial inner membrane with resultant defects in oxidative metabolism may be partially responsible for hepatocellular injury in iron overload. We examined the effects of iron-induced lipid peroxidation in vitro on hepatic mitochondrial morphology and function and determined if various inhibitors of free-radical-mediated injury could be protective. Normal rat liver mitochondria were prepared by differential centrifugation and were incubated with 1, 2, and 3 microM Fe2+, NADPH, and with and without oxygen radical scavengers, iron chelators, and antioxidants. There was a direct linear relationship between the concentration of added iron and the degree of lipid peroxidation as measured by malondialdehyde (MDA) production (r = .85). With 3 microM Fe2+ there was a decrease in the respiratory control ratio (RCR) for all four substrates tested; this decrease in RCR was due to a decrease in the state 3 respiratory rate for all substrates, with no changes in the state 4 respiratory rate for glutamate, beta-hydroxybutyrate, or succinate. Oxygen radical scavengers failed to prevent iron-induced lipid peroxidation or to protect against associated mitochondrial dysfunction. Iron chelators and antioxidants prevented MDA formation and mitochondrial function was maintained. Iron-induced lipid peroxidation in vitro produces an irreversible inhibitory defect in mitochondrial electron transport that may be specific at complex IV (cytochrome oxidase).
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D005296:Ferrous Compounds / Q000633:toxicity*; D005609:Free Radicals; D007425:Intracellular Membranes / Q000187:drug effects / Q000648:ultrastructure; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000975:Antioxidants; D002614:Chelating Agents; D005296:Ferrous Compounds; D005609:Free Radicals; D008054:Lipid Peroxides; D008563:Membrane Lipids; C020748:ferrous sulfate; D010100:Oxygen