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Environmental Toxicology and... Mar 2015Deferasirox (commercially formulated as Exjade(®)) is one of the effective iron chelators used in treatment of iron overload diseases. In this study the effect of this...
Deferasirox (commercially formulated as Exjade(®)) is one of the effective iron chelators used in treatment of iron overload diseases. In this study the effect of this substance for chromosome aberration, sister chromatid exchange and mitotic index was studied by in vitro (by using human peripheral lymphocytes) and in vivo (by using rat) analysis. Deferasirox increased the sister chromatid exchange frequency in all tested concentrations and periods in vitro. Also, in the presence of metabolic activator, the substance led to a statistically significant increase in the sister chromatid exchange frequencies only at high concentration. While in in vitro analysis the substance significantly increased abnormal cell percentages in all concentrations, in in vivo study the substance increased chromosome aberrations only in two concentrations at 12h treatment. In the cultured lymphocytes, deferasirox showed cytotoxicity by significantly reducing proliferation index and mitotic index values. While in the presence of metabolic activation it did not affect the proliferation index frequency, it had a stimulant effect on the mitotic index frequency. Deferasirox reduced significantly the mitotic index value in the bone marrow cells especially in high concentration and short treatment period (12h).
Topics: Adult; Animals; Benzoates; Bone Marrow Cells; Cells, Cultured; Chromosome Aberrations; Deferasirox; Female; Humans; Iron Chelating Agents; Lymphocytes; Male; Mutagens; Rats; Sister Chromatid Exchange; Triazoles; Young Adult
PubMed: 25733130
DOI: 10.1016/j.etap.2015.02.001 -
European Journal of Ophthalmology Apr 2024Deferasirox is the only iron chelator available in oral formulation and a rare cause of pigmentary retinopathy. We report the first case of multimodal imaging in an...
INTRODUCTION
Deferasirox is the only iron chelator available in oral formulation and a rare cause of pigmentary retinopathy. We report the first case of multimodal imaging in an adult with deferasirox retinopathy.
METHODS
Case report and literature review, with search terms including deferasirox retinopathy and deferasirox toxicity.
RESULTS
A 63-year-old man with end stage renal disease and transfusion-dependent anemia on deferasirox for one year presented with asymptomatic pigment epitheliopathy. Optical coherence tomography featured outer retinal and retinal pigment epithelial discontinuity corresponding to hypoautofluorescence on fundus autofluorescence and blocking on fluorescein angiography. Multifocal electroretinography revealed subtle reduction in all amplitudes.
CONCLUSIONS
Retinal examinations should be considered for patients requiring chronic administration of deferasirox.
PubMed: 38562036
DOI: 10.1177/11206721241245740 -
International Journal of Hematology Jan 2018Iron overload (IOL) starts to develop in MDS patients before they become transfusion-dependent because ineffective erythropoiesis suppresses hepcidin production in the... (Review)
Review
Iron overload (IOL) starts to develop in MDS patients before they become transfusion-dependent because ineffective erythropoiesis suppresses hepcidin production in the liver and thus leads to unrestrained intestinal iron uptake. However, the most important cause of iron overload in MDS is chronic transfusion therapy. While transfusion dependency by itself is a negative prognostic factor reflecting poor bone marrow function, the ensuing transfusional iron overload has an additional dose-dependent negative impact on the survival of patients with lower risk MDS. Cardiac dysfunction appears to be important in this context, as a consequence of chronic anemia, age-related cardiac comorbidity, and iron overload. Another potential problem is iron-related endothelial dysfunction. There is some evidence that with increasing age, high circulating iron levels worsen the atherosclerotic phenotype. Transfusional IOL also appears to aggravate bone marrow failure in MDS, through unfavorable effects on mesenchymal stromal cells as well a hematopoietic cells, particularly erythroid precursors. Patient series and clinical trials have shown that the iron chelators deferoxamine and deferasirox can improve hematopoiesis in a minority of transfusion-dependent patients. Analyses of registry data suggest that iron chelation provides a survival benefit for patients with MDS, but data from a prospective randomized clinical trial are still lacking.
Topics: Benzoates; Blood Transfusion; Deferasirox; Deferoxamine; Erythropoiesis; Hepcidins; Humans; Intestinal Mucosa; Iron; Iron Chelating Agents; Iron Overload; Liver; Myelodysplastic Syndromes; Transfusion Reaction; Triazoles
PubMed: 29177643
DOI: 10.1007/s12185-017-2367-1 -
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 -
Nature Reviews. Nephrology Oct 2014In 2005, the oral iron chelator deferasirox was approved by the FDA for clinical use as a first-line therapy for blood-transfusion-related iron overload. Nephrotoxicity... (Review)
Review
In 2005, the oral iron chelator deferasirox was approved by the FDA for clinical use as a first-line therapy for blood-transfusion-related iron overload. Nephrotoxicity is the most serious and frequent adverse effect of deferasirox treatment. This nephrotoxicity can present as an acute or chronic decrease in glomerular filtration rate (GFR). Features of proximal tubular dysfunction might also be present. In clinical trials and observational studies, GFR is decreased in 30-100% of patients treated with deferasirox, depending on dose, method of assessment and population studied. Nephrotoxicity is usually nonprogressive and/or reversible and rapid iron depletion is one of several risk factors. Scarce data are available on the molecular mechanisms of nephrotoxicity and the reasons for the specific proximal tubular sensitivity to the drug. Although deferasirox promotes apoptosis of cultured proximal tubular cells, the trigger has not been well characterized. Observational studies are required to track current trends in deferasirox prescription, assess the epidemiology of deferasirox nephrotoxicity in routine clinical practice, explore the effect on outcomes of various monitoring and dose-adjustment protocols and elucidate the long-term consequences of the different features of nephrotoxicity. Deferasirox nephrotoxicity can be more common in the elderly; thus, specific efforts should be dedicated to investigate the effect of deferasirox use in this group of patients.
Topics: Acute Kidney Injury; Benzoates; Deferasirox; Glomerular Filtration Rate; Humans; Iron Chelating Agents; Iron Overload; Renal Insufficiency, Chronic; Transfusion Reaction; Triazoles
PubMed: 25048549
DOI: 10.1038/nrneph.2014.121 -
Annals of the New York Academy of... Mar 2016Regular red cell transfusions used to treat thalassemia cause iron loading that must be treated with chelation therapy. Morbidity and mortality in thalassemia major are... (Review)
Review
Regular red cell transfusions used to treat thalassemia cause iron loading that must be treated with chelation therapy. Morbidity and mortality in thalassemia major are closely linked to the adequacy of chelation. Chelation therapy removes accumulated iron and detoxifies iron, which can prevent and reverse much of the iron-mediated organ injury. Currently, three chelators are commercially available--deferoxamine, deferasirox, and deferiprone--and each can be used as monotherapy or in combination. Close monitoring of hepatic and cardiac iron burden is central to tailoring chelation. Other factors, including properties of the individual chelators, ongoing transfusional iron burden, and patient preference, must be considered. Monotherapy generally is utilized if the iron burden is in an acceptable or near-acceptable range and the dose is adjusted accordingly. Combination chelation often is employed for patients with high iron burden, iron-related organ injury, or where adverse effects of chelators preclude administration of an appropriate chelator dose. The combination of deferoxamine and deferiprone is the best studied, but increasing data are available on the safety and efficacy of newer chelator combinations, including deferasirox with deferoxamine and the oral-only combination of deferasirox with deferiprone. The expanding chelation repertoire should enable better control of iron burden and improved outcomes.
Topics: Animals; Blood Transfusion; Chelation Therapy; Clinical Trials as Topic; Humans; Iron Chelating Agents; Thalassemia
PubMed: 27186943
DOI: 10.1111/nyas.13088 -
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 -
Journal of Biochemical and Molecular... Sep 2023During the period of COVID-19, the occurrences of mucormycosis in immunocompromised patients have increased significantly. Mucormycosis (black fungus) is a rare and... (Review)
Review
During the period of COVID-19, the occurrences of mucormycosis in immunocompromised patients have increased significantly. Mucormycosis (black fungus) is a rare and rapidly progressing fungal infection associated with high mortality and morbidity in India as well as globally. The causative agents for this infection are collectively called mucoromycetes which are the members of the order Mucorales. The diagnosis of the infection needs to be performed as soon as the occurrence of clinical symptoms which differs with types of Mucorales infection. Imaging techniques magnetic resonance imaging or computed tomography scan, culture testing, and microscopy are the approaches for the diagnosis. After the diagnosis of the infection is confirmed, rapid action is needed for the treatment in the form of antifungal therapy or surgery depending upon the severity of the infection. Delaying in treatment declines the chances of survival. In antifungal therapy, there are two approaches first-line therapy (monotherapy) and combination therapy. Amphotericin B (1) and isavuconazole (2) are the drugs of choice for first-line therapy in the treatment of mucormycosis. Salvage therapy with posaconazole (3) and deferasirox (4) is another approach for patients who are not responsible for any other therapy. Adjunctive therapy is also used in the treatment of mucormycosis along with first-line therapy, which involves hyperbaric oxygen and cytokine therapy. There are some drugs like VT-1161 (5) and APX001A (6), Colistin, SCH 42427, and PC1244 that are under clinical trials. Despite all these approaches, none can be 100% successful in giving results. Therefore, new medications with favorable or little side effects are required for the treatment of mucormycosis.
Topics: Humans; Antifungal Agents; Mucormycosis; COVID-19; Amphotericin B; Mucorales
PubMed: 37345721
DOI: 10.1002/jbt.23417 -
Acta Haematologica 2019
Topics: Deferasirox; Humans; Iron Chelating Agents; Iron Overload; Thalassemia
PubMed: 31189159
DOI: 10.1159/000497431