Neurobehavioural Toxicity of Iron Oxide Nanoparticles in Mice.
Iron oxide nanoparticles (Fe2O3-NPs) are widely used in various biomedical applications, extremely in neurotheranostics. Simultaneously, Fe2O3-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 Fe2O3-NPs is very limited. In this regard, adult male mice were intraperitoneally administered with Fe2O3-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 Fe2O3-NP-treated animals. Damages to blood-brain barrier permeability by Fe2O3-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 Fe2O3-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 Fe2O3-NP-exposed brain regions which confirms DNA damage and apoptosis. Thus, repeated Fe2O3-NP exposure causes neurobehavioural impairments by nanoparticle accumulation, oxidative stress and apoptosis in the mouse brain.
Molecular Toxicology Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore, Tamil Nadu, 641 046, India.
Vasanth
V
Dhakshinamoorthy
Molecular Toxicology Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore, Tamil Nadu, 641 046, India.
Vijayprakash
V
Manickam
Molecular Toxicology Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore, Tamil Nadu, 641 046, India. ekas2009@buc.edu.in.
Ekambaram
E
Perumal
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D003711:Demyelinating Diseases / Q000139:chemically induced*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005290:Ferric Compounds / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007859:Learning Disabilities / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D053768:Metal Nanoparticles / Q000633:toxicity*; D051379:Mice; D009069:Movement Disorders / Q000209:etiology* / Q000473:pathology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011596:Psychomotor Disorders / Q000139:chemically induced* / Q000473:pathology
D000975:Antioxidants; D005290:Ferric Compounds; C000499:ferric oxide; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D011065:Poly(ADP-ribose) Polymerases; D000110:Acetylcholinesterase; D053148:Caspase 3
Apoptosis; Fe2O3-NPs; Locomotor behaviour; Oxidative stress; Spatial memory