How to manage iron toxicity in post-allogeneic hematopoietic stem cell transplantation?

Kontoghiorghes, George J.

doi:10.1080/17474086.2020.1719359

Cited by 21 publications

(39 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, despite the many reports of the toxicity of NTBI in experimental settings, its clinical significance in thalassaemia and other iron loaded conditions is questioned and is not utilized in clinical practice. The major concerns in relation to iron overloaded conditions associated with tissue damage, as well as the overall morbidity and mortality of iron loaded patients in clinical practice, are mostly associated with the evaluation of the level of excess iron deposition in major organs [ 10 , 11 , 12 , 152 , 153 ]. In this context, excess deposited iron, mainly in the form of haemosiderin, can be found in organs of iron loaded patients, including the heart, liver, spleen and pancreas, and monitored using magnetic resonance imaging (MRI) T2* relaxation times [ 154 , 155 , 156 , 157 , 158 ].…”

Section: Toxicity Implications Of the Interaction Of Iron And Ascomentioning

confidence: 99%

“…These include observational studies asserting that iron losses, including urinary iron excretion, are substantially reduced in iron-deficient individuals, and are substantially increased in iron loaded patients in comparison to normal individuals [ 150 , 195 , 225 , 226 ]. Similar questions have arisen as to how iron loaded transplanted thalassaemia patients could achieve steady reductions in body iron, and in some cases have even achieved normal iron body levels several years after transplantation, without the use of chelation therapy or venesection [ 4 , 11 , 227 , 228 , 229 ].…”

Section: Future Therapeutic Strategies and Health Implications Ofmentioning

confidence: 99%

“…Iron metabolic imbalance is generally associated with a number of serious conditions, such as iron deficiency anaemia, which affects about a third to a quarter of the world’s population [ 7 ]. In contrast, many hundreds of thousands of patients with chronic haematological and malignant diseases, including thalassaemia, sickle cell anaemia, haematopoietic stem cell transplantation, aplastic anaemia and cancer, are affected by iron overload due to multiple red blood cell transfusions for the treatment of the refractory anaemia [ 8 , 9 , 10 , 11 ]. Similarly, iron overload caused by increased gastrointestinal iron absorption in the inherited disease idiopathic haemochromatosis affects thousands of people, especially populations of Caucasian origin [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Trying to Solve the Puzzle of the Interaction of Ascorbic Acid and Iron: Redox, Chelation and Therapeutic Implications

et al. 2020

Self Cite

View full text Add to dashboard Cite

Iron and ascorbic acid (vitamin C) are essential nutrients for the normal growth and development of humans, and their deficiency can result in serious diseases. Their interaction is of nutritional, physiological, pharmacological and toxicological interest, with major implications in health and disease. Millions of people are using pharmaceutical and nutraceutical preparations of these two nutrients, including ferrous ascorbate for the treatment of iron deficiency anaemia and ascorbate combination with deferoxamine for increasing iron excretion in iron overload. The main function and use of vitamin C is its antioxidant activity against reactive oxygen species, which are implicated in many diseases of free radical pathology, including biomolecular-, cellular- and tissue damage-related diseases, as well as cancer and ageing. Ascorbic acid and its metabolites, including the ascorbate anion and oxalate, have metal binding capacity and bind iron, copper and other metals. The biological roles of ascorbate as a vitamin are affected by metal complexation, in particular following binding with iron and copper. Ascorbate forms a complex with Fe3+ followed by reduction to Fe2+, which may potentiate free radical production. The biological and clinical activities of iron, ascorbate and the ascorbate–iron complex can also be affected by many nutrients and pharmaceutical preparations. Optimal therapeutic strategies of improved efficacy and lower toxicity could be designed for the use of ascorbate, iron and the iron–ascorbate complex in different clinical conditions based on their absorption, distribution, metabolism, excretion, toxicity (ADMET), pharmacokinetic, redox and other properties. Similar strategies could also be designed in relation to their interactions with food components and pharmaceuticals, as well as in relation to other aspects concerning personalized medicine.

show abstract

Section: Toxicity Implications Of the Interaction Of Iron And Ascomentioning

confidence: 99%

Section: Future Therapeutic Strategies and Health Implications Ofmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Trying to Solve the Puzzle of the Interaction of Ascorbic Acid and Iron: Redox, Chelation and Therapeutic Implications

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Postmortem studies of patients dying shortly after HSCT revealed levels of hepatic and BM iron comparable with the levels observed in patients with HFE hemochromatosis (158). Iron overload in HSCT may cause heart and pancreas damage and promote microbial infection (69,95). It may also directly affect the BM niche and impair hematopoietic reconstitution, as suggested by the negative prognostic impact of pretransplantation elevated serum ferritin levels in HSCT outcomes (7).…”

Section: Iron In Hematopoiesismentioning

confidence: 79%

The Role of Iron in Benign and Malignant Hematopoiesis

Sinha

Reis

Guerra

et al. 2021

Antioxidants & Redox Signaling

View full text Add to dashboard Cite

Significance: Iron is an essential element required for sustaining a normal healthy life. However, an excess amount of iron in the bloodstream and tissue generates toxic hydroxyl radicals through Fenton reactions. Henceforth, a balance in iron concentration is extremely important to maintain cellular homeostasis in both normal hematopoiesis and erythropoiesis. Iron deficiency or iron overload can impact hematopoiesis and is associated with many hematological diseases. Recent Advances: The mechanisms of action of key iron regulators such as erythroferrone and the discovery of new drugs, such as ACE-536/luspatercept, are of potential interest to treat hematological disorders, such as b-thalassemia. New therapies targeting inflammation-induced ineffective erythropoiesis are also in progress. Furthermore, emerging evidences support differential interactions between iron and its cellular antioxidant responses of hematopoietic and neighboring stromal cells. Both iron and its systemic regulator, such as hepcidin, play a significant role in regulating erythropoiesis. Critical Issues: Significant pre-clinical studies are on the way and new drugs targeting iron metabolism have been recently approved or are undergoing clinical trials to treat pathological conditions with impaired erythropoiesis such as myelodysplastic syndromes or b-thalassemia. Future Directions: Future studies should explore how iron regulates hematopoiesis in both benign and malignant conditions. Antioxid. Redox Signal. 00, 000-000.

show abstract

“…In particular, one of these disorders thalassemia has the highest morbidity and mortality rate in relation to iron or metal toxicity worldwide [ 8 , 9 ]. A rapidly expanding category of iron loaded patients currently estimated to about 0.5 million are those undergoing hematopoietic stem cell transplantation, which is a widely used form of treatment for many hematological malignancies and genetic disorders [ 10 , 11 , 12 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Iron and Chelation in Biochemistry and Medicine: New Approaches to Controlling Iron Metabolism and Treating Related Diseases

Kontoghiorghes

Kontoghiorghe

2020

Cells

125

174

View full text Add to dashboard Cite

Iron is essential for all living organisms. Many iron-containing proteins and metabolic pathways play a key role in almost all cellular and physiological functions. The diversity of the activity and function of iron and its associated pathologies is based on bond formation with adjacent ligands and the overall structure of the iron complex in proteins or with other biomolecules. The control of the metabolic pathways of iron absorption, utilization, recycling and excretion by iron-containing proteins ensures normal biologic and physiological activity. Abnormalities in iron-containing proteins, iron metabolic pathways and also other associated processes can lead to an array of diseases. These include iron deficiency, which affects more than a quarter of the world’s population; hemoglobinopathies, which are the most common of the genetic disorders and idiopathic hemochromatosis. Iron is the most common catalyst of free radical production and oxidative stress which are implicated in tissue damage in most pathologic conditions, cancer initiation and progression, neurodegeneration and many other diseases. The interaction of iron and iron-containing proteins with dietary and xenobiotic molecules, including drugs, may affect iron metabolic and disease processes. Deferiprone, deferoxamine, deferasirox and other chelating drugs can offer therapeutic solutions for most diseases associated with iron metabolism including iron overload and deficiency, neurodegeneration and cancer, the detoxification of xenobiotic metals and most diseases associated with free radical pathology.

show abstract

How to manage iron toxicity in post-allogeneic hematopoietic stem cell transplantation?

Cited by 21 publications

References 29 publications

Trying to Solve the Puzzle of the Interaction of Ascorbic Acid and Iron: Redox, Chelation and Therapeutic Implications

Trying to Solve the Puzzle of the Interaction of Ascorbic Acid and Iron: Redox, Chelation and Therapeutic Implications

The Role of Iron in Benign and Malignant Hematopoiesis

Iron and Chelation in Biochemistry and Medicine: New Approaches to Controlling Iron Metabolism and Treating Related Diseases

Contact Info

Product

Resources

About