Exposure to Iron Oxide Nanoparticles Coated with Phospholipid-Based Polymeric Micelles Induces Biochemical and Histopathological Pulmonary Changes in Mice

Abstract

The biochemical and histopathological changes induced by the exposure to iron oxide nanoparticles coated with phospholipid-based polymeric micelles (IONPs-PM) in CD-1 mice lungs were analyzed. After 2, 3, 7 and 14 days following the intravenous injection of IONPs-PM (5 and 15 mg Fe/kg bw), lactate dehydrogenase (LDH) activity, oxidative stress parameters and the expression of Bax, Bcl-2, caspase-3 and TNF-α were evaluated in lung tissue. An increase of catalase (CAT) and glutathione reductase (GR) activities on the second day followed by a decrease on the seventh day, as well as a decline of lactate dehydrogenase (LDH), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity on the third and seventh day were observed in treated groups vs. controls. However, all these enzymatic activities almost fully recovered on the 14th day. The reduced glutathione (GSH) and protein thiols levels decreased significantly in nanoparticles-treated groups and remained diminished during the entire experimental period; by contrast malondialdehyde (MDA) and protein carbonyls increased between the 3rd and 14th day of treatment vs. control. Relevant histopathological modifications were highlighted using Hematoxylin and Eosin (H&E) staining. In addition, major changes in the expression of apoptosis markers were observed in the first week, more pronounced for the higher dose. The injected IONPs-PM generated a dose-dependent decrease of the mouse lung capacity, which counteracted oxidative stress, thus creating circumstances for morphopathological lesions and oxidation processes.

Cerium Oxide Nanoparticles in Lung Acutely Induce Oxidative Stress, Inflammation, and DNA Damage in Various Organs of Mice

“…The antioxidant SOD was significantly decreased by CeO 2 NPs, whereas that of GSH was increased. The decrease of SOD activity indicates that it has been consumed as a result of oxidative stress [22, 45, 46]. The increase of GSH in the lung suggests that the development of oxidative stress is followed by an adaptive reaction that balances the potentially damaging activity of ROS by antioxidant defence mechanisms [28, 47].…”

Exposure to Iron Oxide Nanoparticles Coated with Phospholipid-Based Polymeric Micelles Induces Renal Transitory Biochemical and Histopathological Changes in Mice

“…The IONPs encapsulated in phospholipid-based polymeric micelles used in this study were designed and prepared as previously described [ 17 ]. Hydrophobic magnetite NPs stabilized with oleic acid were synthesized using a solvothermal method with minor modifications [ 19 ].…”

“…The obtained NPs were monodispersed (polydispersity index of 0.086) with an average size of 12.5 nm, and the average size of the micelle-encapsulated IONPs was 21.5 nm, slightly higher than the size of unloaded (empty) micelles prepared from phospholipid polymeric derivative DSPE-PEG [ 17 ]. The zeta potentials of unloaded (−30.1 mV) and loaded micelles (−20.7 mV) were similar to those previously reported in the literature [ 19 ].…”

“…The specific activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione reductase (GR), glutathione-S-transferase (GST), and glucose-6-phosphate dehydrogenase (G6PDH) were measured in kidney tissue homogenates, as previously described [ 17 , 21 , 22 ]. All the enzymatic activities were expressed as specific activities (U/mg of protein) and represented as % from controls.…”

“…Although there is an increasing number of studies devoted to understanding the interaction of IONPs with biological systems, published data on the biodistribution and toxicity of IONPs are not consistent, which might be due to the variation in IONPs characteristics and experimental conditions. Thus far, data on the in vivo toxicity of IONPs encapsulated in polymeric micelles have been reported in mice lung [ 17 ], spleen [ 18 ], and liver [ 14 ].…”