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Uncoupling and oxidative stress in liver mitochondria isolated from rats with acute iron overload

机译:急性铁超负荷大鼠肝线粒体的解偶联和氧化应激

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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.
机译:对于铁超负荷引起的细胞损伤的病因学的一种假设是,其过量选择性地影响线粒体。在这里,我们测试了急性铁超负荷对从单次腹膜内注射大鼠中分离出的肝线粒体的作用。 500 mg / kg铁-右旋糖酐。该处理增加了线粒体中铁的含量(从21±4增加到130±7 nmol / mg蛋白),并引起脂质过氧化和谷胱甘肽氧化。铁治疗的大鼠的线粒体显示出较低的呼吸控制率和较高的静息呼吸。铁处理引起的线粒体解偶联并不影响磷酸化效率或ATP水平,这表明解偶联是针对急性铁超负荷的线粒体保护机制。因此,作为线粒体氧化还原稳态机制的活性氧(ROS)/ H + 泄漏对可在急性铁负荷的线粒体中起保护作用。

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