Abstract
Background:
Excessive iron accumulation leads to iron toxicity in the brain; however the underlying mechanism is unclear. We investigated the effects of iron overload induced by high iron-diet consumption on brain mitochondrial function, brain synaptic plasticity and learning and memory. Iron chelator (deferiprone) and antioxidant (n-acetyl cysteine) effects on iron-overload brains were also studied.
Methodology:
Male Wistar rats were fed either normal diet or high iron-diet consumption for 12 weeks, after which rats in each diet group were treated with vehicle or deferiprone (50 mg/kg) or n-acetyl cysteine (100 mg/kg) or both for another 4 weeks. High iron-diet consumption caused brain iron accumulation, brain mitochondrial dysfunction, impaired brain synaptic plasticity and cognition, blood-brain-barrier breakdown, and brain apoptosis. Although both iron chelator and antioxidant attenuated these deleterious effects, combined therapy provided more robust results.
Conclusion:
In conclusion, this is the first study demonstrating that combined iron chelator and anti-oxidant therapy completely restored brain function impaired by iron overload.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antioxidants / administration & dosage*
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Apoptosis
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Blood-Brain Barrier / metabolism
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Brain / drug effects
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Brain / metabolism
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Brain / pathology
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Brain / physiopathology
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Brain Diseases / drug therapy
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Brain Diseases / etiology*
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Brain Diseases / physiopathology*
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Cognition
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Diet / adverse effects
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Disease Models, Animal
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Drug Therapy, Combination
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Iron / metabolism
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Iron Chelating Agents / administration & dosage*
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Iron Overload / complications*
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Iron Overload / drug therapy*
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Male
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Maze Learning
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Mitochondria / drug effects
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Mitochondria / metabolism
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Mitochondria / pathology
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Oxidative Stress
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Rats
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Treatment Outcome
Substances
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Antioxidants
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Iron Chelating Agents
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Iron
Grants and funding
This work was supported by grants from the Thailand Research Fund TRF-BRG (SC), TRF-RTA5580006 (NC), Faculty of Medicine Chiang Mai University Endowment Fund (NC), National Research Council of Thailand (SC), Thailand Research Fund through the Royal Golden Jubilee Program (PHD/0248/2552: JS and SC), and Chiang Mai University Excellent Center Award (NC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.