Uncoupling and oxidative stress in liver mitochondria isolated from rats with acute iron overload.
One hypothesis for the etiology of cell damage arising from iron overload is that its excess selectively affects mitochondria. Here we tested the effects of acute iron overload on liver mitochondria isolated from rats subjected to a single dose of i.p. 500 mg/kg iron-dextran. The treatment increased the levels of iron in mitochondria (from 21 +/- 4 to 130 +/- 7 nmol/mg protein) and caused both lipid peroxidation and glutathione oxidation. The mitochondria of iron-treated rats showed lower respiratory control ratio in association with higher resting respiration. The mitochondrial uncoupling elicited by iron-treatment did not affect the phosphorylation efficiency or the ATP levels, suggesting that uncoupling is a mitochondrial protective mechanism against acute iron overload. Therefore, the reactive oxygen species (ROS)/H+ leak couple, functioning as a mitochondrial redox homeostatic mechanism could play a protective role in the acutely iron-loaded mitochondria.
Departamento de Investigaciones Biomédicas, Centro de Química Farmacéutica, Calle 200, Esq. 21, Playa, CP 11600, Ciudad de La Habana, Cuba. gilbertopardo@infomed.sld.cu
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D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D007274:Injections, Intraperitoneal; D019190:Iron Overload / Q000139:chemically induced / Q000503:physiopathology*; D007505:Iron-Dextran Complex / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D007505:Iron-Dextran Complex; D005978:Glutathione