Baratli Yosra, Charles Anne-Laure, Wolff Valérie, Ben Tahar Lotfi, Smiri Leila, Bouitbir Jamal, Zoll Joffrey, Sakly Mohsen, Auger Cyril, Vogel Thomas, Abdelmelek Hafedh, Tebourbi Olfa, Geny Bernard
EA 3072, Mitochondries, Stress Oxydant et Protection Musculaire, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, 67000 Strasbourg, France ; Laboratoire de Physiologie Intégrée, Faculté des Sciences de Bizerte, Université de Carthage, 7021 Jarzouna, Tunisia.
EA 3072, Mitochondries, Stress Oxydant et Protection Musculaire, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, 67000 Strasbourg, France.
Biomed Res Int. 2014;2014:474081. doi: 10.1155/2014/474081. Epub 2014 May 6.
We examined the effects of iron oxide nanoparticles (IONPs) on mitochondrial respiratory chain complexes activities and mitochondrial coupling in young (3 months) and middle-aged (18 months) rat liver, organ largely involved in body iron detoxification. Isolated liver mitochondria were extracted using differential centrifugations. Maximal oxidative capacities (V(max), complexes I, III, and IV activities), V(succ) (complexes II, III, and IV activities), and V tmpd, (complex IV activity), together with mitochondrial coupling (V(max)/V0) were determined in controls conditions and after exposure to 250, 300, and 350 μ g/ml Fe3O4 in young and middle-aged rats. In young liver mitochondria, exposure to IONPs did not alter mitochondrial function. In contrast, IONPs dose-dependently impaired all complexes of the mitochondrial respiratory chain in middle-aged rat liver: V(max) (from 30 ± 1.6 to 17.9 ± 1.5; P < 0.001), V(succ) (from 33.9 ± 1.7 to 24.3 ± 1.0; P < 0.01), V(tmpd) (from 43.0 ± 1.6 to 26.3 ± 2.2 µmol O2/min/g protein; P < 0.001) using Fe3O4 350 µg/ml. Mitochondrial coupling also decreased. Interestingly, 350 μ g/ml Fe3O4 in the form of Fe(3+) solution did not impair liver mitochondrial function in middle-aged rats. Thus, IONPs showed a specific toxicity in middle-aged rats suggesting caution when using it in old age.
我们研究了氧化铁纳米颗粒（IONPs）对年轻（3个月）和中年（18个月）大鼠肝脏线粒体呼吸链复合物活性及线粒体偶联的影响，肝脏是身体铁解毒的主要器官。采用差速离心法提取分离的肝脏线粒体。在对照条件下以及年轻和中年大鼠暴露于250、300和350μg/ml Fe3O4后，测定最大氧化能力（V(max)，复合物I、III和IV活性）、V(succ)（复合物II、III和IV活性）和V(tmpd)（复合物IV活性）以及线粒体偶联（V(max)/V0）。在年轻肝脏线粒体中，暴露于IONPs未改变线粒体功能。相反，IONPs剂量依赖性地损害中年大鼠肝脏线粒体呼吸链的所有复合物：使用350μg/ml Fe3O4时，V(max)（从30±1.6降至17.9±1.5；P<0.001），V(succ)（从33.9±1.7降至24.3±1.0；P<0.01），V(tmpd)（从43.0±1.6降至26.3±2.2μmol O2/分钟/克蛋白；P<0.001）。线粒体偶联也降低。有趣的是，Fe(3+)溶液形式的350μg/ml Fe3O4并未损害中年大鼠肝脏线粒体功能。因此，IONPs在中年大鼠中表现出特异性毒性，提示在老年使用时需谨慎。
