Research Article
Age Modulates Fe
3
O
4
Nanoparticles Liver Toxicity:
Dose-Dependent Decrease in Mitochondrial Respiratory
Chain Complexes Activities and Coupling in
Middle-Aged as Compared to Young Rats
Yosra Baratli,
1,2
Anne-Laure Charles,
1
Valérie Wolff,
1
Lotfi Ben Tahar,
3
Leila Smiri,
3
Jamal Bouitbir,
1
Joffrey Zoll,
1,4
Mohsen Sakly,
2
Cyril Auger,
5
Thomas Vogel,
1
Hafedh Abdelmelek,
2
Olfa Tebourbi,
2
and Bernard Geny
1,4
1
EA 3072, Mitochondries, Stress Oxydant et Protection Musculaire, F´ ed´ eration de M´ edecine Translationnelle de Strasbourg,
Universit´ e de Strasbourg, 67000 Strasbourg, France
2
Laboratoire de Physiologie Int´ egr´ ee, Facult´ e des Sciences de Bizerte, Universit´ e de Carthage, 7021 Jarzouna, Tunisia
3
Laboratoire de Synth` ese et Structures de Nanomat´ eriaux, UR11ES30, Facult´ e des Sciences de Bizerte,
Universit´ e de Carthage, 7021 Jarzouna, Tunisia
4
Service de Physiologie et d’Explorations Fonctionnelles, Pˆ ole de Pathologie oracique, NHC, 67000 Strasbourg, France
5
UMR CNRS 7213-Laboratoire de Biophotonique et Pharmacologie, Facult´ e de Pharmacie, Universit´ e de Strasbourg,
74 route du Rhin, 67401 Illkirch, France
Correspondence should be addressed to Bernard Geny; bernard.geny@chru-strasbourg.fr
Received 10 February 2014; Revised 3 April 2014; Accepted 4 April 2014; Published 6 May 2014
Academic Editor: N. Chandrasekaran
Copyright © 2014 Yosra Baratli et al. his is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
We examined the efects 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
detoxiication. Isolated liver mitochondria were extracted using diferential centrifugations. Maximal oxidative capacities (
max
,
complexes I, III, and IV activities),
succ
(complexes II, III, and IV activities), and
tmpd
, (complex IV activity), together with
mitochondrial coupling (
max
/
0
) were determined in controls conditions and ater exposure to 250, 300, and 350 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:
max
(from 30 ±
1.6 to 17.9 ± 1.5; < 0.001),
succ
(from 33.9 ± 1.7 to 24.3 ± 1.0; < 0.01),
tmpd
(from 43.0 ± 1.6 to 26.3 ± 2.2 mol O
2
/min/g protein;
< 0.001) using Fe
3
O
4
350 g/ml. Mitochondrial coupling also decreased. Interestingly, 350 g/ml Fe
3
O
4
in the form of Fe
3+
solution did not impair liver mitochondrial function in middle-aged rats. hus, IONPs showed a speciic toxicity in middle-aged
rats suggesting caution when using it in old age.
1. Introduction
Because of their unique properties, some nanoparticles have
been approved for clinical use like iron oxide nanoparticles
(IONPs). IONPs hold immense potential in a vast variety of
biomedical applications such as magnetic resonance imaging
(MRI), targeted delivery of drugs or genes, tissue engineering,
targeted destruction of tumor tissue through hyperthermia,
magnetic transfections, iron detection, chelation therapy, and
tissue engineering [1–4]. Reports demonstrate that IONPs
have the ability to assess focal hepatic lesions [5] and to label
human hepatocytes [6].
However, nanoparticles pose a high health risk because of
their ability to reach every part of the organs and tissues and
their interaction with cellular functions.
Concerning NP clearance, it is known that they are
primarily phagocytozed by macrophages in the liver (Kupfer
cells) [7]. hus, the largest detoxiication organ of human
Hindawi Publishing Corporation
BioMed Research International
Volume 2014, Article ID 474081, 10 pages
http://dx.doi.org/10.1155/2014/474081