Review
Biochemistry & Molecular Biology
Yen-Chien Lee, Chi-Tai Yen, Yen-Ling Lee, Rong-Jane Chen
Summary: Thalassemia is a common genetic disorder, and Thalassemia intermedia is a non-transfusion-dependent type. Iron overload is a common issue in Thalassemia intermedia patients. The effectiveness of iron chelation therapy in improving patient outcomes is still debated.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Alkistis Adramerina, Nikoleta Printza, Emmanouel Hatzipantelis, Symeon Symeonidis, Labib Tarazi, Aikaterini Teli, Marina Economou
Summary: Thalassemia is a hereditary anemia that requires regular blood transfusions and chelation therapy. The new deferasirox film-coated tablet (DFX FCT) offers a more convenient and well-tolerated treatment option, although it may lead to increased adverse events in younger patients. The study confirmed the safety of DFX FCT in older children, but higher doses were required for effective chelation.
Review
Pediatrics
Martin Scoglio, Maria Domenica Cappellini, Emanuela D'Angelo, Mario G. Bianchetti, Sebastiano A. G. Lava, Carlo Agostoni, Gregorio P. Milani
Summary: Deferasirox as a first-line therapy for iron overload may lead to kidney damage characterized by tubular injury. Patients may exhibit abnormal urinary findings and electrolyte disturbances, requiring physicians to carefully prescribe the lowest efficacious dose to minimize adverse effects.
Article
Chemistry, Multidisciplinary
Axel Steinbrueck, Adam C. Sedgwick, Hai-Hao Han, Michael Y. Zhao, Sajal Sen, Dan-Ying Huang, Yi Zang, Jia Li, Xiao-Peng He, Jonathan L. Sessler
Summary: In this study, strategic functionalization of the FDA approved chelator deferasirox was conducted to produce organelle-targeting iron chelators with enhanced activity against A549 lung cancer cells. Derivative 8 exhibited improved antiproliferative activity compared to the original compound 1, and was shown to preferentially localize within the lysosome through fluorescent cell imaging.
CHEMICAL COMMUNICATIONS
(2021)
Article
Pharmacology & Pharmacy
Archita Venugopal Menon, Jonghan Kim
Summary: This study investigates the impact of iron on doxorubicin-induced cardiotoxicity and finds that ABCB8 mediates the efflux of doxorubicin. High iron increases the retention and toxicity of doxorubicin, while iron deficiency improves this effect. The results are further validated in a mouse model of hereditary hemochromatosis.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Cell Biology
Xiaomin Wang, Ye Li, Li Han, Jie Li, Cun Liu, Changgang Sun
Summary: Iron overload is a high risk factor for many diseases, while flavonoids have been found to affect iron status and may act as potential complementary therapies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ping Kwan, Amy Ho, Larry Baum
Summary: The accumulation of iron may contribute to Alzheimer's disease (AD) and other tauopathies. An oral iron chelator, desferasirox, was tested in transgenic animal models and showed potential in reducing hyperphosphorylated tau, a protein associated with AD and tauopathies.
Article
Multidisciplinary Sciences
Andrea Piolatto, Paola Berchialla, Sarah Allegra, Silvia De Francia, Giovanni Battista Ferrero, Antonio Piga, Filomena Longo
Summary: Deferasirox (DFX) is the newest chelator used to treat iron overload in iron-loading anemias, with Film-Coated Tablets (FCT) showing higher bioavailability and superior scalability compared to Dispersible Tablets (DT). FCT exhibited a significant dose-response correlation for serum ferritin variation, while both formulations showed an increased risk of renal impairment that was reversible under monitoring, indicating the effectiveness and safety of DFX for tailoring treatment.
SCIENTIFIC REPORTS
(2021)
Article
Hematology
Jassada Buaboonnam, Chayamon Takpradit, Vip Viprakasit, Nattee Narkbunnam, Nassawee Vathana, Kamon Phuakpet, Kleebsabai Sanpakit, Bunchoo Pongtanakul
Summary: This study retrospectively reviewed the outcomes of 22 patients with transfusion-dependent thalassemia who had poor responses to once-daily deferasirox and were subsequently treated with twice-daily dosing of deferasirox. Results showed that the TDD-DFX treatment approach appeared to be effective in refractory patients with a favorable long-term safety profile, warranting further studies with larger groups and pharmacogenetic analyses.
MEDITERRANEAN JOURNAL OF HEMATOLOGY AND INFECTIOUS DISEASES
(2021)
Article
Biochemistry & Molecular Biology
Ying Liu, Carine Fillebeen, Anik Forest, Amy Botta, Thibault V. Varin, Andre Marette, Yan Burelle, Christine Des Rosiers, Kostas Pantopoulos, Gary Sweeney
Summary: This study using the Th3/+ mouse model found that altered lipid metabolism and gut microbiota may be related to the development of cardiomyopathy in thalassemia. These findings are important for understanding the early biomarkers and therapeutic targets for the development of cardiomyopathy in thalassemia.
Article
Pediatrics
Rajeswari Rethinaswamy DivakarJose, C. G. Delhikumar, G. Ram Kumar
Summary: The study aimed to evaluate the efficacy and safety of dual oral iron chelation therapy in reducing iron overload in transfusion-dependent thalassemic children. The results showed a significant decrease in serum ferritin levels with the combination therapy, while liver and myocardial iron concentrations did not change significantly. Adverse effects such as red color urine and transient elevation in creatinine and liver enzymes were observed during the study period.
INDIAN JOURNAL OF PEDIATRICS
(2021)
Article
Chemistry, Multidisciplinary
Wenya Feng, Yuanjing Xiao, Chuanfang Zhao, Zhanming Zhang, Wei Liu, Juan Ma, Tomas Ganz, Junliang Zhang, Sijin Liu
Summary: Excess iron accumulation can lead to genetic disorders or occur after repeated transfusions. Iron chelation therapy is crucial for preventing iron toxicity in these patients. However, current iron chelators have limitations, necessitating the search for new agents. A library of new deferric amine compounds (DFAs), synthesized based on the properties of conventional chelators, shows promising efficacy in binding iron and ameliorating iron overload in murine models. Additionally, the compound DFA1 suppresses iron-induced ferroptosis by modulating intracellular signaling. This study introduces a new approach for developing iron chelators to treat iron overload.
Review
Multidisciplinary Sciences
Yesim Aydinok
Summary: Combination chelation therapy is a viable option for transfusion-dependent thalassemia patients who have not achieved iron balance with monotherapy or need intensified treatment for rapid iron reduction. It allows for a more personalized approach, improving tolerability, adherence, and quality of life. Real-life data highlights the importance of compliance in achieving meaningful reduction in iron overload compared to monotherapy.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2023)
Article
Nanoscience & Nanotechnology
Lidong Yu, Mingyue He, Sihan Liu, Xinyue Dou, Li Li, Ning Gu, Bingsheng Li, Zhiguo Liu, Guixue Wang, Jianglin Fan
Summary: This paper reports the Fe3+ chelation and therapy of iron overload nonalcoholic fatty liver disease (NAFLD) using fluorescent egg white-based carbon dots (EWCDs) obtained through microwave-assisted pyrolysis method. The high-sensitivity sensor EWCDs show a high correlation between fluorescence emission and Fe3+ concentration in low concentration ranges, with high biocompatibility and specific binding of Fe3+ both in vivo and in vitro. As a novel nano-iron-chelator, EWCDs can successfully attenuate the production of lethal reactive oxygen species, prevent hepatocyte apoptosis, regulate fatty acid metabolism, and alleviate inflammation. Ultimately, they alleviate NAFLD induced by iron overload in zebrafish.
ACS APPLIED MATERIALS & INTERFACES
(2021)
Article
Pediatrics
Morgane Pondrom, Fabrice Monpoux, Fanny Rocher, Nadia Gastaut, Carole Bailly-Piccini, Maryline Poiree
Summary: Beta thalassemias are hemoglobin disorders related to a defect in beta-globin chain production, often leading to transfusion dependence and iron overload. A case study of a patient with beta(+) major transfusion-dependent thalassemia showed successful tolerance induction to deferasirox after severe reactions to deferoxamine, deferiprone, and agranulocytosis. This protocol may be useful for pediatric hematology teams dealing with multiple iron chelator reactions in children with iron overload.
ARCHIVES DE PEDIATRIE
(2021)