Age Modulates Fe3O4Nanoparticles Liver Toxicity: Dose-Dependent Decrease in Mitochondrial Respiratory Chain Complexes Activities and Coupling in Middle-Aged as Compared to Young Rats

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 / V 0 ) were determined in controls conditions and after exposure to 250, 300, and 350  μ g/ml Fe 3 O 4 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  µ mol O 2 /min/g protein; P < 0.001) using Fe 3 O 4 350 µ g/ml. Mitochondrial coupling also decreased. Interestingly, 350  μ g/ml Fe 3 O 4 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.