Neurobehavioural Toxicity of Iron Oxide Nanoparticles in Mice

Abstract

Iron oxide nanoparticles (FeO-NPs) are widely used in various biomedical applications, extremely in neurotheranostics. Simultaneously, FeO-NP usage is of alarming concern, as its exposure to living systems causes deleterious effects due to its redox potential. However, study on the neurobehavioural impacts of FeO-NPs is very limited. In this regard, adult male mice were intraperitoneally administered with FeO-NPs (25 and 50 mg/kg body weight) once a week for 4 weeks. A significant change in locomotor behaviour and spatial memory was observed in FeO-NP-treated animals. Damages to blood-brain barrier permeability by FeO-NPs and their accumulation in brain regions were evidenced by Evan's blue staining, iron estimation and Prussian blue staining. Elevated nitric oxide, acetylcholinesterase, lactate dehydrogenase leakage and demyelination were observed in the FeO-NP-exposed brain tissues. Imbalanced levels of ROS generation and antioxidant defence mechanism (superoxide dismutase and catalase) cause damages to lipids, proteins and DNA. PARP and cleaved caspase 3 expression levels were found to be increased in the FeO-NP-exposed brain regions which confirms DNA damage and apoptosis. Thus, repeated FeO-NP exposure causes neurobehavioural impairments by nanoparticle accumulation, oxidative stress and apoptosis in the mouse brain.

Toxicity of Fe2O3 nanoparticles on human blood lymphocytes

“…On the other hand, it has been shown that high levels of ROS can cause damage to macromolecules . The results of our study are in agreement with previous studies …”

“…Malondialdehyde is one of the important indicators for evaluating LPO . The results of our study in this regard are also in agreement with previous studies . Fe 2 O 3 NPs cause OS by disturbing the status of oxidants and antioxidants .…”

“…Fe 2 O 3 NPs cause OS by disturbing the status of oxidants and antioxidants . A decrease in the GSH level and increase in the GSSG level support the collapse in the redox state of the cell . We have shown that exposure to Fe 2 O 3 NPs reduces GSH levels and increases GSSG levels in human lymphocytes.…”

“…NPs, due to their small size and high reactivity, easily enter the body via different routes . Studies have highlighted concerns about the risk of exposure of living organisms to Fe 2 O 3 NPs . However, no studies have so far been conducted to evaluate the human blood lymphocytes toxicity (due to the Fe 2 O 3 NPs) in in vitro models.…”

“…We have shown that exposure to Fe 2 O 3 NPs in a dose and time‐dependent pattern leads to an increase in the level of ROS in human lymphocytes. Previous studies have shown that metal oxide NPs such as Fe 2 O 3 NPs are capable of generating ROS (as a maim mechanism) through Fenton's reaction . Studies show that mitochondria are one of the sources of cellular ROS generation .…”