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Iron-induced Oxidative Stress and Anxiety-like Behavior in Wistar Rats Following Systemic Iron Administration.
Karima Maaroufi1, Afef Moulahi2, Yassine Khadhraoui2
1Higher Institute of Biotechnology of Beja, Laboratory Functional Physiology and Bio-resources Valorisation, University of Jendouba, Avenue Habib Bourguiba, BP 382, Beja, 9000, Tunisia. karimahedhli@yahoo.fr.
Biological Trace Element Research
|November 15, 2025
Summary
Systemic iron administration in rats increased anxiety-like behaviors and brain iron levels. This excess iron led to oxidative stress, particularly in the hippocampus and prefrontal cortex, linking iron dysregulation to anxiety.
Area of Science:
- Neuroscience
- Biochemistry
- Toxicology
Background:
- Iron is vital for brain function, but its dysregulation, leading to excess or deficiency, is implicated in neurodegeneration.
- Iron accumulation in the brain is linked to cognitive deficits and oxidative stress.
- The relationship between iron homeostasis disruption and anxiety-like behaviors is not fully understood.
Purpose of the Study:
- To investigate the effects of systemic iron administration on anxiety-like behavior in rats.
- To determine if iron excess in specific brain regions correlates with anxiety and oxidative stress markers.
Main Methods:
- Rats received daily iron administration for 15 days.
- Anxiety-like behaviors were assessed using four established models: light/dark room, unfamiliar environment, elevated plus-maze, and open-field tests.
- Iron content and oxidative stress biomarkers (catalase, superoxide dismutase, malondialdehyde) were measured in the hippocampus, prefrontal cortex, striatum, and cerebellum.
Main Results:
- Iron-treated rats displayed significantly increased anxiety-like behaviors compared to controls.
- Elevated iron levels and altered oxidative stress markers (increased malondialdehyde, decreased catalase and superoxide dismutase) were observed in the brains of iron-treated rats.
- These changes were particularly pronounced in the medial prefrontal cortex and hippocampus.
Conclusions:
- Systemic iron administration leads to iron accumulation and oxidative stress in the brain.
- This iron dysregulation is associated with increased anxiety-like behaviors.
- The findings highlight a potential link between iron overload, oxidative stress, and anxiety, relevant to neurodegenerative disorders.

