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Journal of Toxicology 2022Patients suffering from iron overload can experience serious complications. In such patients, various organs, such as endocrine glands and liver, can be damaged.... (Review)
Review
Patients suffering from iron overload can experience serious complications. In such patients, various organs, such as endocrine glands and liver, can be damaged. Although iron is a crucial element for life, iron overload can be potentially toxic for human cells due to its role in generating free radicals. In the past few decades, there has been a major improvement in the survival of patients who suffer from iron overload due to the application of iron chelation therapy in clinical practice. In clinical use, deferoxamine, deferiprone, and deferasirox are the three United States Food and Drug Administration-approved iron chelators. Each of these iron chelators is well known for the treatment of iron overload in various clinical conditions. Based on several up-to-date studies, this study explained iron overload and its clinical symptoms, introduced each of the above-mentioned iron chelators, and evaluated their advantages and disadvantages with an emphasis on combination therapy, which in recent studies seems a promising approach. In numerous clinical conditions, due to the lack of accurate indicators, choosing a standard approach for iron chelation therapy can be difficult; therefore, further studies on the issue are still required. This study aimed to introduce each of these iron chelators, combination therapy, usage doses, specific clinical applications, and their advantages, toxicity, and side effects.
PubMed: 35571382
DOI: 10.1155/2022/4911205 -
Blood Oct 2020
Topics: Aged, 80 and over; Anemia, Sideroblastic; Arteriosclerosis; Biopsy; Blood Transfusion; Blood Vessels; Bone Marrow; Deferasirox; Female; Humans; Iron; Iron Overload; Metals, Heavy; Myelodysplastic-Myeloproliferative Diseases; Thrombocytosis; Transfusion Reaction; Treatment Failure
PubMed: 33091139
DOI: 10.1182/blood.2020007779 -
International Journal of Molecular... Jul 2022Iron is a crucial element for mammalian cells, considering its intervention in several physiologic processes. Its homeostasis is finely regulated, and its alteration... (Review)
Review
Iron is a crucial element for mammalian cells, considering its intervention in several physiologic processes. Its homeostasis is finely regulated, and its alteration could be responsible for the onset of several disorders. Iron is closely related to inflammation; indeed, during inflammation high levels of interleukin-6 cause an increased production of hepcidin which induces a degradation of ferroportin. Ferroportin degradation leads to decreased iron efflux that culminates in elevated intracellular iron concentration and consequently iron toxicity in cells and tissues. Therefore, iron chelation could be considered a novel and useful therapeutic strategy in order to counteract the inflammation in several autoimmune and inflammatory diseases. Several iron chelators are already known to have anti-inflammatory effects, among them deferiprone, deferoxamine, deferasirox, and Dp44mT are noteworthy. Recently, eltrombopag has been reported to have an important role in reducing inflammation, acting both directly by chelating iron, and indirectly by modulating iron efflux. This review offers an overview of the possible novel biological effects of the iron chelators in inflammation, suggesting them as novel anti-inflammatory molecules.
Topics: Animals; Benzoates; Deferasirox; Deferiprone; Deferoxamine; Inflammation; Iron; Iron Chelating Agents; Iron Overload; Mammals; Pyridones
PubMed: 35887336
DOI: 10.3390/ijms23147977 -
Mediterranean Journal of Hematology and... 2018Thalassemia incorporates a broad clinical spectrum characterized by decreased or absent production of normal hemoglobin leading to decreased red blood cell survival and... (Review)
Review
Thalassemia incorporates a broad clinical spectrum characterized by decreased or absent production of normal hemoglobin leading to decreased red blood cell survival and ineffective erythropoiesis. Chronic iron overload remains an inevitable complication resulting from regular blood transfusions (transfusion-dependent) and/or increased iron absorption (mainly non-transfusion-dependent thalassemia), requiring adequate treatment to prevent the significant associated morbidity and mortality. Iron chelation therapy has become a cornerstone in the management of thalassemia patients, leading to improvements in their outcome and quality of life. Deferasirox (DFX), an oral iron chelating agent, is approved for use in transfusion dependent and non-transfusion-dependent thalassemia and has shown excellent efficacy in this setting. We herein present an updated review of the role of deferasirox in thalassemia, exploring over a decade of experience, which has documented its effectiveness and convenience; in addition to its manageable safety profile.
PubMed: 30416698
DOI: 10.4084/MJHID.2018.066 -
Cureus Nov 2023Despite the established efficacy of iron chelation therapy in transfusion-induced iron-overloaded patients, there is no universal agreement regarding the choice of an... (Review)
Review
Despite the established efficacy of iron chelation therapy in transfusion-induced iron-overloaded patients, there is no universal agreement regarding the choice of an optimal chelating regimen. Deferasirox (DFX) and deferiprone (DFP) are two oral iron chelators, and combination usage demonstrated effectiveness as an alternative to monotherapies in patients with a limited response to monotherapy. The present systematic review aimed to assess the evidence regarding the outcomes of combined DFP and DFX in iron-overloaded patients. An online search was conducted in PubMed, Scopus, Web of Science, and CENTRAL databases. Interventional and observational studies that assessed the outcomes of combined DFP and DFX in iron-overloaded patients were included. Eleven studies (12 reports) were considered in this meta-analysis. The studies included dual iron chelation strategies for a number of diagnoses. Single-arm studies (n =7) showed a reduction of serum ferritin, which reached the level of statistical significance in three studies. Likewise, most studies reported a numerical reduction in liver iron concentration (LIC) and increased cardiac MRI-T2* values after chelating therapy. Alternatively, comparative studies showed no significant difference in post-treatment serum ferritin between DFX plus DFP and DFX/DFP plus deferoxamine (DFO). The adherence to combination therapy was good to average in nearly 66.7-100% of the patients across four studies. One study reported a poor adherence rate. The combined regimen was generally tolerable, with no reported incidence of serious adverse events among the included studies. In conclusion, the DFP and DFX combination is a safe and feasible option for iron overload patients with a limited response to monotherapy.
PubMed: 38058350
DOI: 10.7759/cureus.48276