Characteristics of Fe(II)ATP complex-induced damage to the rat liver mitochondrial membrane.
It is well established that several iron complexes can induce oxidative damage in hepatic mitochondrial membranes by catalyzing the formation of OH radicals and/or by promoting lipid peroxidation. This is a relevant process for the molecular basis of iron overload diseases. The present work demonstrates that Fe(II)ATP complexes (5-50 microM) promote an oxygen consumption burst in a suspension of isolated rat liver mitochondria (either in the absence or presence of Antimycin A), caused mainly by lipid peroxidation. Fe(II)ATP alone induced small levels of oxygen uptake but no burst. The time course of Fe(II)ATP oxidation to Fe(II)ATP in the extramitochondrial media also reveals a simultaneous 'burst phase'. The iron chelator Desferal (DFO) or the chain-break antioxidant butylated hydroxytoluene (BHT) fully prevented both lipid peroxidation (quantified as oxygen uptake burst) and mitochondrial swelling. DFO and BHT were capable of stopping the ongoing process of peroxidation at any point of their addition to the mitochondrial suspension. Conversely, DFO and BHT only halted the Fe(II)ATP-induced mitochondrial swelling at the onset of the process. Fe(II)ATP could also cause the collapse of mitochondrial potential, which was protected by BHT if added at the onset of the damaging process. These results, as well as correlation studies between peroxidation and mitochondrial swelling, suggest that a two phase process is occurring during Fe(II)ATP-induced mitochondrial damage: one dependent and another independent of lipid peroxidation. The involvement of lipid peroxidation in the overall process of mitochondrial membrane injury is discussed.
Hermes-Lima
M
M
Departamento de Bioquímica, UNICAMP, Campinas, Brazil.
Castilho
R F
RF
Meinicke
A R
AR
Vercesi
A E
AE
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology; D005296:Ferrous Compounds / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000187:drug effects; D015227:Lipid Peroxidation; D008564:Membrane Potentials; D008930:Mitochondria, Liver / Q000187:drug effects*; D008933:Mitochondrial Swelling; D008956:Models, Chemical; D018384:Oxidative Stress; D010101:Oxygen Consumption; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
D005296:Ferrous Compounds; D002084:Butylated Hydroxytoluene; D000255:Adenosine Triphosphate; D002374:Catalase; D013482:Superoxide Dismutase; D003676:Deferoxamine