Abstract
Our main aim is to make a contribution to the establishment of sources of oxidants as the key factors in understanding the role that oxidants and oxidative stress play in the pathogenesis of neurodegeneration, i.e. in the progression of Alzheimer’s disease (AD). Our original observation pointed out the main difference between the hemoglobin and methemoglobin degradation, did from the heme oxygenation when a hemoglobin results in ferrous (Fe2+) iron, but methemoglobin catabolism produces ferric (Fe3+) iron. The methemoglobin plays a role of the carrier, the donor of cytotoxic and redox- active ferric (Fe3+) iron, and it also acts as the originator of neurodegenerative diseases. The abundant and permanent source of redox- active ferric (Fe3+) iron which, without Ferrous-Ferric inversions, has “in situ” direct impact on endothelial small vessels in the brain accumulates and increases the rate of capillary endothelial cell apoptosis and possibly crosses into brain parenchyma to the astrocytes, glia, neurons, and other neuronal cells. Our understanding of the transport and neuronal accumulation of ferric (Fe3+) iron points to how microvessels are organized into a well-structured neurovascular unit with harmful consequences to the brain. Our previously conducted research found that the neonatal jaundice incidence (p=0.034), heart murmur at a later age (p=0.011) and mild disorders in children and adults such as dyslalia and learning/memory impairments (p=0.002) were significantly higher than in children and adults of control mothers without pregnancy methemoglobinemia. The consequence are performed as initial brain iron harmful effects from the mother-fetal pregnancy methemoglobinemia complication, and according to our hypothesis in humans could be followed with the neuronal death, the disease aging process, and leading finally to the severe disorders as AD, PD and other neurodegenerative diseases.
Highlights
It is still not known why iron levels are abnormally high in some regions of the brain in neurodegenerative disorders and it is not clear whether iron accumulation in the brain is the initial event that causes neuronal death or is a consequence of the disease process
Our results point out the consequence of the toxic environmental oxidants, caused by brain damage with a view to the role of methemoglobin catabolism in pregnancy as the source of ferric (Fe3+) iron form concentrated in various brain regions
Methemoglobin and hemolysis both occur as a result of oxidative stress, but the prevalent difference between them is that methemoglobin is a reversible phenomenon whereas hemolysis, which occurs as a result of oxidative stress on the erythrocyte membrane, is an irreversible event
Summary
It is still not known why iron levels are abnormally high in some regions of the brain in neurodegenerative disorders and it is not clear whether iron accumulation in the brain is the initial event that causes neuronal death or is a consequence of the disease process. Methemoglobin by itself and heme have prooxidant properties and induce structural and functional changes in the vascular endothelium [2,3]. These changes include cell growth arrest, senescence, morphological alterations and cell apoptosis, and they lead to both vessel trombosis and endothelial cell denudation under the influence of redox-active ferric iron (Fe3+), which is a product of heme-oxygenase, responsible for methemoglobin-heme degradation
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