title: Age modulates Fe3O4 nanoparticles liver toxicity: dose-dependent decrease in mitochondrial respiratory chain complexes activities and coupling in middle-aged as compared to young rats.
abstract: 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.
authors.affiliation: 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.
authors.forename: Yosra
authors.initials: Y
authors.lastname: Baratli
authors.affiliation: EA 3072, Mitochondries, Stress Oxydant et Protection Musculaire, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, 67000 Strasbourg, France.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Charles
authors.affiliation: EA 3072, Mitochondries, Stress Oxydant et Protection Musculaire, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, 67000 Strasbourg, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Wolff
authors.affiliation: Laboratoire de Synthèse et Structures de Nanomatériaux, UR11ES30, Faculté des Sciences de Bizerte, Université de Carthage, 7021 Jarzouna, Tunisia.
authors.forename: Lotfi
authors.initials: L
authors.lastname: Ben Tahar
authors.affiliation: Laboratoire de Synthèse et Structures de Nanomatériaux, UR11ES30, Faculté des Sciences de Bizerte, Université de Carthage, 7021 Jarzouna, Tunisia.
authors.forename: Leila
authors.initials: L
authors.lastname: Smiri
authors.affiliation: EA 3072, Mitochondries, Stress Oxydant et Protection Musculaire, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, 67000 Strasbourg, France.
authors.forename: Jamal
authors.initials: J
authors.lastname: Bouitbir
authors.affiliation: EA 3072, Mitochondries, Stress Oxydant et Protection Musculaire, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, 67000 Strasbourg, France ; Service de Physiologie et d'Explorations Fonctionnelles, Pôle de Pathologie Thoracique, NHC, 67000 Strasbourg, France.
authors.forename: Joffrey
authors.initials: J
authors.lastname: Zoll
authors.affiliation: Laboratoire de Physiologie Intégrée, Faculté des Sciences de Bizerte, Université de Carthage, 7021 Jarzouna, Tunisia.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Sakly
authors.affiliation: UMR CNRS 7213-Laboratoire de Biophotonique et Pharmacologie, Faculté de Pharmacie, Université de Strasbourg, 74 route du Rhin, 67401 Illkirch, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Auger
authors.affiliation: EA 3072, Mitochondries, Stress Oxydant et Protection Musculaire, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, 67000 Strasbourg, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Vogel
authors.affiliation: Laboratoire de Physiologie Intégrée, Faculté des Sciences de Bizerte, Université de Carthage, 7021 Jarzouna, Tunisia.
authors.forename: Hafedh
authors.initials: H
authors.lastname: Abdelmelek
authors.affiliation: Laboratoire de Physiologie Intégrée, Faculté des Sciences de Bizerte, Université de Carthage, 7021 Jarzouna, Tunisia.
authors.forename: Olfa
authors.identifier: 0000-0001-6778-5410
authors.initials: O
authors.lastname: Tebourbi
authors.affiliation: EA 3072, Mitochondries, Stress Oxydant et Protection Musculaire, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, 67000 Strasbourg, France ; Service de Physiologie et d'Explorations Fonctionnelles, Pôle de Pathologie Thoracique, NHC, 67000 Strasbourg, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Geny
mesh_terms: D000367:Age Factors; D000818:Animals; D042967:Electron Transport Complex I / Q000187:drug effects; D005290:Ferric Compounds / Q000633:toxicity*; D008099:Liver / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects*; D053758:Nanoparticles / Q000633:toxicity*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats
chemical_list: D005290:Ferric Compounds; C000499:ferric oxide; D042967:Electron Transport Complex I