Combined therapy of iron chelator and antioxidant completely restores brain dysfunction induced by iron toxicity

• Main Authors: Jirapas Sripetchwandee, Noppamas Pipatpiboon, Nipon Chattipakorn, Siriporn Chattipakorn
• Format: Journal
• Published: 2018
• Subjects: Agricultural and Biological Sciences; Biochemistry, Genetics and Molecular Biology
• Online Access: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84896460432&origin=inward; http://cmuir.cmu.ac.th/jspui/handle/6653943832/53097
• Institution: Chiang Mai University

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 ironoverload 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. © 2014 Sripetchwandee et al.