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Iron Load Toxicity in Medicine: From Molecular and Cellular Aspects to Clinical Implications

Iron is essential for all organisms and cells. Diseases of iron imbalance affect billions of patients, including those with iron overload and other forms of iron toxicity. Excess iron load is an adverse prognostic factor for all diseases and can cause serious organ damage and fatalities following ch...

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Autor principal: Kontoghiorghes, George J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10454416/
https://www.ncbi.nlm.nih.gov/pubmed/37629109
http://dx.doi.org/10.3390/ijms241612928
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author Kontoghiorghes, George J.
author_facet Kontoghiorghes, George J.
author_sort Kontoghiorghes, George J.
collection PubMed
description Iron is essential for all organisms and cells. Diseases of iron imbalance affect billions of patients, including those with iron overload and other forms of iron toxicity. Excess iron load is an adverse prognostic factor for all diseases and can cause serious organ damage and fatalities following chronic red blood cell transfusions in patients of many conditions, including hemoglobinopathies, myelodyspasia, and hematopoietic stem cell transplantation. Similar toxicity of excess body iron load but at a slower rate of disease progression is found in idiopathic haemochromatosis patients. Excess iron deposition in different regions of the brain with suspected toxicity has been identified by MRI T2* and similar methods in many neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. Based on its role as the major biological catalyst of free radical reactions and the Fenton reaction, iron has also been implicated in all diseases associated with free radical pathology and tissue damage. Furthermore, the recent discovery of ferroptosis, which is a cell death program based on free radical generation by iron and cell membrane lipid oxidation, sparked thousands of investigations and the association of iron with cardiac, kidney, liver, and many other diseases, including cancer and infections. The toxicity implications of iron in a labile, non-protein bound form and its complexes with dietary molecules such as vitamin C and drugs such as doxorubicin and other xenobiotic molecules in relation to carcinogenesis and other forms of toxicity are also discussed. In each case and form of iron toxicity, the mechanistic insights, diagnostic criteria, and molecular interactions are essential for the design of new and effective therapeutic interventions and of future targeted therapeutic strategies. In particular, this approach has been successful for the treatment of most iron loading conditions and especially for the transition of thalassemia from a fatal to a chronic disease due to new therapeutic protocols resulting in the complete elimination of iron overload and of iron toxicity.
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spelling pubmed-104544162023-08-26 Iron Load Toxicity in Medicine: From Molecular and Cellular Aspects to Clinical Implications Kontoghiorghes, George J. Int J Mol Sci Review Iron is essential for all organisms and cells. Diseases of iron imbalance affect billions of patients, including those with iron overload and other forms of iron toxicity. Excess iron load is an adverse prognostic factor for all diseases and can cause serious organ damage and fatalities following chronic red blood cell transfusions in patients of many conditions, including hemoglobinopathies, myelodyspasia, and hematopoietic stem cell transplantation. Similar toxicity of excess body iron load but at a slower rate of disease progression is found in idiopathic haemochromatosis patients. Excess iron deposition in different regions of the brain with suspected toxicity has been identified by MRI T2* and similar methods in many neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. Based on its role as the major biological catalyst of free radical reactions and the Fenton reaction, iron has also been implicated in all diseases associated with free radical pathology and tissue damage. Furthermore, the recent discovery of ferroptosis, which is a cell death program based on free radical generation by iron and cell membrane lipid oxidation, sparked thousands of investigations and the association of iron with cardiac, kidney, liver, and many other diseases, including cancer and infections. The toxicity implications of iron in a labile, non-protein bound form and its complexes with dietary molecules such as vitamin C and drugs such as doxorubicin and other xenobiotic molecules in relation to carcinogenesis and other forms of toxicity are also discussed. In each case and form of iron toxicity, the mechanistic insights, diagnostic criteria, and molecular interactions are essential for the design of new and effective therapeutic interventions and of future targeted therapeutic strategies. In particular, this approach has been successful for the treatment of most iron loading conditions and especially for the transition of thalassemia from a fatal to a chronic disease due to new therapeutic protocols resulting in the complete elimination of iron overload and of iron toxicity. MDPI 2023-08-18 /pmc/articles/PMC10454416/ /pubmed/37629109 http://dx.doi.org/10.3390/ijms241612928 Text en © 2023 by the author. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Kontoghiorghes, George J.
Iron Load Toxicity in Medicine: From Molecular and Cellular Aspects to Clinical Implications
title Iron Load Toxicity in Medicine: From Molecular and Cellular Aspects to Clinical Implications
title_full Iron Load Toxicity in Medicine: From Molecular and Cellular Aspects to Clinical Implications
title_fullStr Iron Load Toxicity in Medicine: From Molecular and Cellular Aspects to Clinical Implications
title_full_unstemmed Iron Load Toxicity in Medicine: From Molecular and Cellular Aspects to Clinical Implications
title_short Iron Load Toxicity in Medicine: From Molecular and Cellular Aspects to Clinical Implications
title_sort iron load toxicity in medicine: from molecular and cellular aspects to clinical implications
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10454416/
https://www.ncbi.nlm.nih.gov/pubmed/37629109
http://dx.doi.org/10.3390/ijms241612928
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