Protective effect of methylene blue in iron-induced neurotoxicity

• Published in: Medical hypotheses 2024-04, Vol.185, p.111299, Article 111299
• Main Authors: Scigliano, Giulio, Augusto Scigliano, Giuseppe, Ronchetti, Gabriele
• Format: Article
• Language: English
• Subjects: Cerebral hemosiderin; Cerebral iron; Iron deposits in the brain; Methylene blue; Oxidative stress
• ISSN: 0306-9877; 1532-2777
• DOI: 10.1016/j.mehy.2024.111299

Iron deposits have been identified as an intriguing pathological finding in the brain. Although generally considered benign, and, to a certain degree, necessary for various biochemical processes and functions, recent research suggests that abnormal iron deposits may exert harmful effects on brain tissue. Excessive iron accumulation in the brain, due to an imbalance in iron homeostasis and exacerbated by endogenous hydrogen peroxide (H2O2), can contribute to neurodegenerative diseases like Alzheimer's and Parkinson's diseases. This occurs through the Fenton reaction, where iron and H2O2 produce highly reactive hydroxyl radicals (•OH), causing oxidative stress and damaging cellular components. This oxidative damage leads to neuronal dysfunction and death, promoting aggregation of misfolded proteins and the progression of neurodegenerative diseases. Methylene blue, a versatile medication used in methemoglobinemia treatment and diagnostics, shows promise in the prevention of possible brain damage from iron deposits. It may act by inhibiting the Fenton reaction, and reducing hydroxyl radical production. By reducing oxidative stress, methylene blue can mitigate iron-induced neurotoxicity in neurodegenerative diseases. We propose early treatment with methylene blue in patients with initial signs of neurodegenerative diseases and excessive iron deposits in the brain detected with Magnetic Resonance Imaging.