271 results on '"deferiprone"'
Search Results
2. Study of Parkinson's Early Stage With Deferiprone (SKY)
- Published
- 2024
3. Cardiac MRI-guided Deferiprone Therapy for Acute Myocardial Infarction Patients (MIRON-DFP)
- Author
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Rohan Dharmakumar, Executive Director, Krannert Cardiovascular Research Center
- Published
- 2024
4. Safety and Efficacy of Early Treatment With Deferiprone in Infants and Young Children (START)
- Published
- 2024
5. Design and development of metal-organic framework-based nanocomposite hydrogels for quantification of deferiprone in exhaled breath condensate.
- Author
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Moharami, Reza, Karimzadeh, Zahra, Soleymani, Jafar, Jouyban-Gharamaleki, Vahid, Khoubnasabjafari, Maryam, Rahimpour, Elaheh, and Jouyban, Abolghasem
- Subjects
- *
FOURIER transform infrared spectroscopy , *X-ray powder diffraction , *TRANSMISSION electron microscopy , *FLUORESCENCE quenching , *METAL-organic frameworks - Abstract
In this study, a novel fluorescence nanoprobe based on Materials of Institute Lavoisier (MIL-101) metal-organic frameworks embedding into the agarose hydrogel is fabricated using a hydrothermal technique. It uses for sensitive quantification of deferiprone in exhaled breath condensate (EBC) samples. The morphology and characterization of MIL-101/agarose nanocomposite hydrogel is studied by transmission electron microscopy, dynamic light scattering instrument, powder X-ray diffraction analysis, and Fourier transform infrared spectroscopy. The probe shows a reasonable fluorescence intensity quenching in the presence of deferiprone due to the interactions between iron centers in MIL-101 (Fe) and deferiprone, which likely form non-fluorescent complexes. The proposed nanoprobe demonstrates a linear calibration curve from 0.005 to 1.5 µg mL− 1 with a detection limit of 0.003 µg mL− 1. The intra- and inter-day precision of the reported method are 0.3% and 0.4% (n = 5, deferiprone concentration = 1.0 µg mL− 1), respectively. This method demonstrates high sensitivity and specificity towards deferiprone in the EBC samples and also presents a sensing platform with simplicity, convenience, fast implementation, and cost-effective in medical monitoring. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
6. Design and development of metal-organic framework-based nanocomposite hydrogels for quantification of deferiprone in exhaled breath condensate
- Author
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Reza Moharami, Zahra Karimzadeh, Jafar Soleymani, Vahid Jouyban-Gharamaleki, Maryam Khoubnasabjafari, Elaheh Rahimpour, and Abolghasem Jouyban
- Subjects
Fluorescence nanoprobe ,MIL-101 MOF ,Nanocomposite hydrogel ,Deferiprone ,Exhaled breath condensate ,Chemistry ,QD1-999 - Abstract
Abstract In this study, a novel fluorescence nanoprobe based on Materials of Institute Lavoisier (MIL-101) metal-organic frameworks embedding into the agarose hydrogel is fabricated using a hydrothermal technique. It uses for sensitive quantification of deferiprone in exhaled breath condensate (EBC) samples. The morphology and characterization of MIL-101/agarose nanocomposite hydrogel is studied by transmission electron microscopy, dynamic light scattering instrument, powder X-ray diffraction analysis, and Fourier transform infrared spectroscopy. The probe shows a reasonable fluorescence intensity quenching in the presence of deferiprone due to the interactions between iron centers in MIL-101 (Fe) and deferiprone, which likely form non-fluorescent complexes. The proposed nanoprobe demonstrates a linear calibration curve from 0.005 to 1.5 µg mL− 1 with a detection limit of 0.003 µg mL− 1. The intra- and inter-day precision of the reported method are 0.3% and 0.4% (n = 5, deferiprone concentration = 1.0 µg mL− 1), respectively. This method demonstrates high sensitivity and specificity towards deferiprone in the EBC samples and also presents a sensing platform with simplicity, convenience, fast implementation, and cost-effective in medical monitoring.
- Published
- 2024
- Full Text
- View/download PDF
7. Long-term Safety and Efficacy of Ferriprox® in Iron Overloaded Patients With Sickle Cell Disease or Other Anemias
- Published
- 2024
8. Uncovering the role of ferroptosis in Bietti crystalline dystrophy and potential therapeutic strategies
- Author
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Chang Shen, Qianjie Yang, Kuangqi Chen, Huiling Ma, Xiawei Wang, Jianping Tong, Ye Shen, and Hongguang Cui
- Subjects
Bietti crystalline dystrophy ,Ferroptosis ,Polyunsaturated fatty acids ,NCOA4 ,Deferiprone ,Medicine ,Cytology ,QH573-671 - Abstract
Abstract Purpose Bietti crystalline dystrophy (BCD) is an inherited retinal degeneration disease caused by mutations in the CYP4V2 gene. Currently, there is no clinical therapy approach available for BCD patients. Previous research has suggested that polyunsaturated fatty acids (PUFAs) may play a significant role in the development of BCD, implicating the involvement of ferroptosis in disease pathogenesis. In this work, we aimed to investigate the interplay between ferroptosis and BCD and to detect potential therapeutic strategies for the disease. Methods Genetic-edited RPE cell line was first established in this study by CRISPR-Cas9 technology. Cyp4v3 (the homologous gene of human CYP4V2) knock out (KO) mice have also been used. Lipid profiling and transcriptome analysis of retinal pigment epithelium (RPE) cells from Cyp4v3 KO mice have been conducted. Ferroptosis phenotypes have been first investigated in BCD models in vitro and in vivo, including lipid peroxidation, mitochondrial changes, elevated levels of reactive oxygen species (ROS), and altered gene expression. Additionally, an iron chelator, deferiprone (DFP), has been tested in vitro and in vivo to determine its efficacy in suppressing ferroptosis and restoring the BCD phenotype. Results Cyp4v3 KO mice exhibited progressive retinal degeneration and lipid accumulation, similar to the BCD phenotype, which was exacerbated by a high-fat diet (HFD). Increased levels of PUFAs, such as EPA (C22:5) and AA (C20:4), were observed in the RPE of Cyp4v3 KO mice. Transcriptome analysis of RPE in Cyp4v3 KO mice revealed changes in genes involved in iron homeostasis, particularly an upregulation of NCOA4, which was confirmed by immunofluorescence. Ferroptosis-related characteristics, including mitochondrial defects, lipid peroxidation, ROS accumulation, and upregulation of related genes, were detected in the RPE both in vitro and in vivo. Abnormal accumulation of ferrous iron was also detected. DFP, an iron chelator administration suppressed ferroptosis phenotype in CYP4V2 mutated RPE. Oral administration of DFP also restored the retinal function and morphology in Cyp4v3 KO mice. Conclusion This study represented the first evidence of the substantial role of ferroptosis in the development of BCD. PUFAs resulting from CYP4V2 mutation may serve as substrates for ferroptosis, potentially working in conjunction with NCOA4-regulated iron accumulation, ultimately leading to RPE degeneration. DFP administration, which chelates iron, has demonstrated its ability to reverse BCD phenotype both in vitro and in vivo, suggesting a promising therapeutic approach in the future.
- Published
- 2024
- Full Text
- View/download PDF
9. Uncovering the role of ferroptosis in Bietti crystalline dystrophy and potential therapeutic strategies.
- Author
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Shen, Chang, Yang, Qianjie, Chen, Kuangqi, Ma, Huiling, Wang, Xiawei, Tong, Jianping, Shen, Ye, and Cui, Hongguang
- Subjects
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DYSTROPHY , *IRON in the body , *UNSATURATED fatty acids , *ORAL drug administration , *IRON chelates , *CHELATING agents , *HOMEOSTASIS , *IRON fertilizers - Abstract
Purpose: Bietti crystalline dystrophy (BCD) is an inherited retinal degeneration disease caused by mutations in the CYP4V2 gene. Currently, there is no clinical therapy approach available for BCD patients. Previous research has suggested that polyunsaturated fatty acids (PUFAs) may play a significant role in the development of BCD, implicating the involvement of ferroptosis in disease pathogenesis. In this work, we aimed to investigate the interplay between ferroptosis and BCD and to detect potential therapeutic strategies for the disease. Methods: Genetic-edited RPE cell line was first established in this study by CRISPR-Cas9 technology. Cyp4v3 (the homologous gene of human CYP4V2) knock out (KO) mice have also been used. Lipid profiling and transcriptome analysis of retinal pigment epithelium (RPE) cells from Cyp4v3 KO mice have been conducted. Ferroptosis phenotypes have been first investigated in BCD models in vitro and in vivo, including lipid peroxidation, mitochondrial changes, elevated levels of reactive oxygen species (ROS), and altered gene expression. Additionally, an iron chelator, deferiprone (DFP), has been tested in vitro and in vivo to determine its efficacy in suppressing ferroptosis and restoring the BCD phenotype. Results: Cyp4v3 KO mice exhibited progressive retinal degeneration and lipid accumulation, similar to the BCD phenotype, which was exacerbated by a high-fat diet (HFD). Increased levels of PUFAs, such as EPA (C22:5) and AA (C20:4), were observed in the RPE of Cyp4v3 KO mice. Transcriptome analysis of RPE in Cyp4v3 KO mice revealed changes in genes involved in iron homeostasis, particularly an upregulation of NCOA4, which was confirmed by immunofluorescence. Ferroptosis-related characteristics, including mitochondrial defects, lipid peroxidation, ROS accumulation, and upregulation of related genes, were detected in the RPE both in vitro and in vivo. Abnormal accumulation of ferrous iron was also detected. DFP, an iron chelator administration suppressed ferroptosis phenotype in CYP4V2 mutated RPE. Oral administration of DFP also restored the retinal function and morphology in Cyp4v3 KO mice. Conclusion: This study represented the first evidence of the substantial role of ferroptosis in the development of BCD. PUFAs resulting from CYP4V2 mutation may serve as substrates for ferroptosis, potentially working in conjunction with NCOA4-regulated iron accumulation, ultimately leading to RPE degeneration. DFP administration, which chelates iron, has demonstrated its ability to reverse BCD phenotype both in vitro and in vivo, suggesting a promising therapeutic approach in the future. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
10. The Effect of Oral Iron Chelator Deferiprone on Iron Overload and Oxidative Stress in Patients with Myelodysplastic Syndromes: A Study by the Israeli MDS Working Group.
- Author
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Merkel, Drorit, Soffer, Shelly, Filanovsky, Kalman, Braester, Andrei, Fibach, Eitan, Dana, Mutaz, Ofran, Yishai, Greenbaum, Uri, Nagler, Arnon, Amitai, Irina, and Mittelman, Moshe
- Subjects
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IRON overload , *POISONS , *IRON chelates , *ERYTHROCYTES , *OXIDATIVE stress , *AGRANULOCYTOSIS - Abstract
Background: Most patients with lower risk myelodysplastic neoplasms or syndromes (MDSs) become RBC transfusion-dependent, resulting in iron overload, which is associated with an increased oxidative stress state. Iron-chelation therapy is applied to attenuate the toxic effects of this state. Deferiprone (DFP) is an oral iron chelator, which is not commonly used in this patient population, due to safety concerns, mainly agranulocytosis. The purpose of this study was to assess the effect of DFP, on oxidative stress parameters in iron-overloaded RBC transfusion-dependent patients with lower risk MDSs. Methods: Adult lower risk MDS patients with a cumulative transfusion burden of >20 red blood cell units and evidence of iron overload (serum ferritin >1,000 ng/mL) were included in this study. DFP was administered (100 mg/kg/day) for 4 months. Blood samples for oxidative stress parameters and iron overload parameters were done at baseline and monthly: reactive oxygen species (ROS), phosphatidylserine, reduced glutathione, membrane lipid peroxidation, serum ferritin, and cellular labile iron pool. The primary efficacy variable was ROS. Tolerability and side effects were recorded as well. A paired t test was applied for statistical analyses. Results: Eighteen patients were treated with DFP. ROS significantly decreased in all cell lineages: median decrease of 58.6% in RBC, 33.3% in PMN, and 39.8% in platelets (p < 0.01 for all). Other oxidative stress markers improved: phosphatidylserine decreased by 57.95%, lipid peroxidase decreased by 141.3%, and reduced gluthathione increased by 72.8% (p < 0.01 for all). The iron-overload marker and cellular labile iron pool decreased by 35% in RBCs, 44.3% in PMN, and 46.3% in platelets (p < 0.01 for all). No significant changes were observed in SF levels. There were no events of agranulocytosis. All AEs were grades 1–2. Conclusions: Herein, we showed preliminary evidence that DFP decreases iron-induced oxidative stress in MDS patients with a good tolerability profile (albeit a short follow-up period). No cases of severe neutropenia or agranulocytosis were reported. The future challenge is to prove that reduction in iron toxicity will eventually be translated into a clinically meaningful improvement. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
11. Improving Routine 89Zr‐Immuno‐PET Applications: Mild Iron Removal Can Favor the Use of Fe‐DFO‐N‐suc‐TFP Ester Over p‐NCS‐Bz‐DFO.
- Author
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Wuensche, Thomas E., Nauta, Sabine, van Dongen, Guus A. M. S., and Vugts, Danielle J.
- Subjects
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RADIOCHEMICAL purification , *ESTERS , *IRON , *DEFEROXAMINE , *RADIOLABELING - Abstract
A key aspect for the applicability of 89Zr‐radioimmunoconjugates is inert modification and radiolabeling. The two commercially available bifunctional variants of the siderophore desferrioxamine (DFO), Fe‐DFO‐N‐suc‐TFP‐ester and p‐NCS‐Bz‐DFO, are most often used for clinical 89Zr‐immuno‐PET. The use of Fe‐DFO‐N‐suc‐TFP‐ester is advantageous with regard to higher radiolysis stability and more facile assessment of radiochemical purity as well as chelator‐to‐mAb ratio. However, not all mAbs withstand the Fe‐removal step at relatively low pH (4–4.5) using EDTA, which is needed after conjugation to allow 89Zr labeling. In this study, it was investigated whether hydroxybenzyl ethylenediamine (HBED) or the clinically approved deferiprone (DFP) can serve as an alternative for EDTA to establish a pH‐independent mild method for Fe‐removal and thereby broaden the applicability of Fe‐DFO‐N‐suc‐TFP‐ester. Carrier‐added [59Fe]Fe‐DFO‐N‐suc‐TFP‐ester was used for mAb modification to enable direct tracking of the Fe‐removal efficiency under various conditions. Whereas incomplete Fe‐removal with HBED was observed at pH 5 or higher, Fe‐removal with DFP was possible at a broad pH range (4–9). This provides a mild, pH‐independent method for Fe‐removal, improving the applicability and attractiveness of Fe‐DFO‐N‐suc‐TFP‐ester for 89Zr‐mAb preparation. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
12. The Importance and Essentiality of Natural and Synthetic Chelators in Medicine: Increased Prospects for the Effective Treatment of Iron Overload and Iron Deficiency.
- Author
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Kontoghiorghes, George J.
- Subjects
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DEFEROXAMINE , *IRON overload , *IRON deficiency anemia , *IRON deficiency , *IRON in the body , *IRON metabolism , *CHELATING agents , *QUERCETIN - Abstract
The supply and control of iron is essential for all cells and vital for many physiological processes. All functions and activities of iron are expressed in conjunction with iron-binding molecules. For example, natural chelators such as transferrin and chelator–iron complexes such as haem play major roles in iron metabolism and human physiology. Similarly, the mainstay treatments of the most common diseases of iron metabolism, namely iron deficiency anaemia and iron overload, involve many iron–chelator complexes and the iron-chelating drugs deferiprone (L1), deferoxamine (DF) and deferasirox. Endogenous chelators such as citric acid and glutathione and exogenous chelators such as ascorbic acid also play important roles in iron metabolism and iron homeostasis. Recent advances in the treatment of iron deficiency anaemia with effective iron complexes such as the ferric iron tri-maltol complex (feraccru or accrufer) and the effective treatment of transfusional iron overload using L1 and L1/DF combinations have decreased associated mortality and morbidity and also improved the quality of life of millions of patients. Many other chelating drugs such as ciclopirox, dexrazoxane and EDTA are used daily by millions of patients in other diseases. Similarly, many other drugs or their metabolites with iron-chelation capacity such as hydroxyurea, tetracyclines, anthracyclines and aspirin, as well as dietary molecules such as gallic acid, caffeic acid, quercetin, ellagic acid, maltol and many other phytochelators, are known to interact with iron and affect iron metabolism and related diseases. Different interactions are also observed in the presence of essential, xenobiotic, diagnostic and theranostic metal ions competing with iron. Clinical trials using L1 in Parkinson's, Alzheimer's and other neurodegenerative diseases, as well as HIV and other infections, cancer, diabetic nephropathy and anaemia of inflammation, highlight the importance of chelation therapy in many other clinical conditions. The proposed use of iron chelators for modulating ferroptosis signifies a new era in the design of new therapeutic chelation strategies in many other diseases. The introduction of artificial intelligence guidance for optimal chelation therapeutic outcomes in personalised medicine is expected to increase further the impact of chelation in medicine, as well as the survival and quality of life of millions of patients with iron metabolic disorders and also other diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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13. Amelioration of nephrotoxicity by targeting ferroptosis: role of NCOA4, IREB2, and SLC7a11 signaling
- Author
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N. Sharawy, B.E. Aboulhoda, M.M. Khalifa, G.N. Morcos, S.A.A.G. Morsy, M.A. Alghamdi, I.M. Khalifa, and W.A. Abd Algaleel
- Subjects
Ferroptosis ,Ferritinophagy ,Iron ,Kidney ,Cisplatin ,Deferiprone ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Nephrotoxicity is a common complication that limits the clinical utility of cisplatin. Ferroptosis is an iron-dependent necrotic cell death program that is mediated by phospholipid peroxidation. The molecular mechanisms that disrupt iron homeostasis and lead to ferroptosis are yet to be elucidated. In this study, we aimed to investigate the involvement of nuclear receptor coactivator 4 (NCOA4), a selective cargo receptor that mediates ferroptosis and autophagic degradation of ferritin in nephrotoxicity. Adult male Sprague-Dawley rats were randomly-assigned to four groups: control group, cisplatin (Cis)-treated group, deferiprone (DEF)-treated group, and Cis+DEF co-treated group. Serum, urine, and kidneys were isolated to perform biochemical, morphometric, and immunohistochemical analysis. Iron accumulation was found to predispose to ferroptotic damage of the renal tubular cells. Treatment with deferiprone highlights the role of ferroptosis in nephrotoxicity. Upregulation of NCOA4 in parallel with low ferritin level in renal tissue seems to participate in iron-induced ferroptosis. This study indicated that ferroptosis may participate in cisplatin-induced tubular cell death and nephrotoxicity through iron-mediated lipid peroxidation. Iron dyshomeostasis could be attributed to NCOA4-mediated ferritin degradation.
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- 2024
- Full Text
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14. Synthesis of Deferiprone as a Widely Used Iron-Chelating Drug for the Treatment of Iron-Overload Diseases
- Author
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Sara Sadeghian, Fateme Zare, Lotfollah Saghaie, and Razieh Sabet
- Subjects
synthesis ,deferiprone ,maltol ,methylamine ,iron chelating agent ,Pharmacy and materia medica ,RS1-441 - Abstract
Thalassemia is a genetic disease that significantly affects human health. The common treatment of thalassemia is the regular injection of red blood cell, which is associated with the accumulation of iron in different tissues of the body, and makes chelation therapy necessary. Deferiprone and deferoxamine are broadly used as iron chelating agents in the vast majority of thalassemia cases. In this study, an efficient method for the synthesis of deferiprone was used by reacting maltol with methylamine in a mixture of water and ethanol as solvent. The structure of deferiprone was assigned using different spectroscopic techniques such as IR, 1H-NMR, and 13C-NMR. The advantages of this pathway are simple, practical, one-pot cascade, mild condition and high yield. The statistics of the Ministry of Health of Iran show the growing trend of deferiprone drug consumption in the country. Therefore, the domestic preparation of this drug can help the pharmaceutical industry in order to reduce costs and make it available for target patients.Keywords: Synthesis, Deferiprone, Maltol, Methylamine, Iron chelating agent.
- Published
- 2024
- Full Text
- View/download PDF
15. Challenges of Iron Chelation in Thalassemic Children
- Author
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Alkistis Adramerina and Marina Economou
- Subjects
thalassemia ,deferoxamine ,deferiprone ,deferasirox ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Thalassemia treatment still relies on supportive care, mainly including blood transfusion and iron chelation therapy. Iron chelation is considered the main factor responsible for the marked improvement in survival rates of thalassemic patients. Hemosiderosis may be prevented if appropriate chelation therapy is offered from early childhood, with timely dose adjustments according to changing body weight and close monitoring of organ iron load. With three iron chelators currently available, the choice of appropriate chelation, either as monotherapy or combined therapy, should be individualized depending on the iron overload of target organs, patient’s age, presence of adverse events and compliance issues, given known limitations related to each agent’s administration.
- Published
- 2024
- Full Text
- View/download PDF
16. Inhibition of ferroptosis reverses heart failure with preserved ejection fraction in mice
- Author
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Yixiao Xiong, Xin Liu, Ling Jiang, Tao Hao, Yanyan Wang, and Tao Li
- Subjects
Heart failure with preserved ejection fraction ,Ferroptosis ,Bioinformatics analysis ,Ferrostatin-1 ,Deferiprone ,Medicine - Abstract
Abstract Background Heart failure with preserved ejection fraction (HFpEF) accounts for approximately 50% of heart failure cases. The molecular mechanisms by which HFpEF leads to impaired diastolic function of the heart have not been clarified, nor have the drugs that target the clinical symptoms of HFpEF patients. Methods HFpEF chip data (GSE180065) was downloaded from the National Center for Biotechnology Information (NCBI) database. Differentially expressed genes (DEGs) were filtered by the limma package in R and processed for GO and KEGG pathway analyses. Then, ferroptosis-related genes in HFpEF were identified by taking the intersection between DEGs and ferroptosis-related genes. CytoHubba and MCODE were used to screen ferroptosis-related hub DEGs in the protein–protein interaction (PPI) network. Establishment of a mouse HFpEF model to validate the transcript levels of ferroptosis-related hub DEGs and ferroptosis-related phenotypes. Transcript levels of ferroptosis-related hub DEGs and HFpEF phenotypic changes in the hearts of HFpEF mice were further examined after the use of ferroptosis inhibitors. Results GO and KEGG enrichment analyses suggested that the DEGs in HFpEF were significantly enriched in ferroptosis-related pathways. A total of 24 ferroptosis-related DEGs were identified between the ferroptosis gene dataset and the DEGs. The established PPI network was further analyzed by CytoHubba and MCODE modules, and 11 ferroptosis-related hub DEGs in HFpEF were obtained. In animal experiments, HFpEF mice showed significant abnormal activation of ferroptosis. The expression trends of the 11 hub DEGs associated with ferroptosis, except for Cdh1, were consistent with the results of the bioinformatics analysis. Inhibition of ferroptosis alters the transcript levels of 11 ferroptosis-related hub DEGs and ameliorates HFpEF phenotypes. Conclusions The present study contributes to a deeper understanding of the specific mechanisms by which ferroptosis is involved in the development of HFpEF and suggests that inhibition of ferroptosis may mitigate the progression of HFpEF. In addition, eleven hub genes were recognized as potential drug binding targets.
- Published
- 2024
- Full Text
- View/download PDF
17. Infratentorial superficial siderosis: report of six cases and review of the literature.
- Author
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Lixia Deng, Yi Lin, Yu Lin, and Weibin Huang
- Subjects
LITERATURE reviews ,PYRAMIDAL tract ,MAGNETIC resonance imaging ,CEREBELLAR ataxia ,SPINAL cord ,EPILEPSY - Abstract
Objectives: To investigate the etiology, clinical manifestations, imaging features, and treatment of patients with infratentorial superficial siderosis (iSS), enhance clinicians' comprehension of this rare disease, and conduct oral deferiprone intervention and subsequent monitoring. Methods: Six patients diagnosed with iSS based on magnetic resonance imaging (MRI) and susceptibility weighted imaging (SWI) were enrolled from 2021 to 2023 at the First Affiliated Hospital of Fujian Medical University. Their clinical datas were summarized, and the etiology and imaging characteristics were analyzed. Follow-up was conducted through telephone or outpatient visits. Results: Among the 6 patients, there were 3 males and 3 females. The onset age ranged from 35 to 71 years, with an average onset age of 53 years. The clinical symptoms mainly included acoustic disturbances (6/6), gait imbalance (6/6), dysolfactory (6/6), cognitive impairment (2/6), epilepsy (2/6), and pyramidal tract sign (2/6). Evidence of superficial siderosis was observed on MRI across the cortex, brainstem, cerebellum, and spinal cord in all patients. T2-space sequence MRI revealed two instances of dural tear. During the follow-up period ranging from 1 month to 3 years, three patients who received oral deferiprone treatment showed improvement, whereas the remaining three patients who declined deferiprone treatment demonstrated progression. Conclusion: The primary clinical manifestations of iSS include bilateral sensorineural hearing disturbances, progressive cerebellar ataxia, and spinal cord lesions. The key diagnostic criteria involve the presence of linear hypointensity on T2-WI in the surface region of the nervous system. Dural tear caused by various factors is considered to be the most common cause of iSS, and its treatment mainly involves surgical intervention for hemorrhagic primary diseases as well as pharmacotherapy with deferiprone. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
18. Synthesis of Deferiprone as a Widely Used Iron-Chelating Drug for the Treatment of Iron-Overload Diseases.
- Author
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Sadeghian, Sara, Zare, Fateme, Saghaie, Lotfollah, and Sabet, Razieh
- Subjects
- *
IRON chelates , *CHELATING agents , *CHELATION therapy , *DRUG utilization , *ERYTHROCYTES - Abstract
Thalassemia is a genetic disease that significantly affects human health. The common treatment of thalassemia is the regular injection of red blood cell, which is associated with the accumulation of iron in different tissues of the body, and makes chelation therapy necessary. Deferiprone and deferoxamine are broadly used as iron chelating agents in the vast majority of thalassemia cases. In this study, an efficient method for the synthesis of deferiprone was used by reacting maltol with methylamine in a mixture of water and ethanol as solvent. The structure of deferiprone was assigned using different spectroscopic techniques such as IR, 1H-NMR, and 13C-NMR. The advantages of this pathway are simple, practical, one-pot cascade, mild condition and high yield. The statistics of the Ministry of Health of Iran show the growing trend of deferiprone drug consumption in the country. Therefore, the domestic preparation of this drug can help the pharmaceutical industry in order to reduce costs and make it available for target patients. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
19. The Oxidative Stress Response Highly Depends on Glucose and Iron Availability in Aspergillus fumigatus.
- Author
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Emri, Tamás, Antal, Károly, Varga, Kinga, Gila, Barnabás Csaba, and Pócsi, István
- Subjects
- *
ASPERGILLUS fumigatus , *OXIDATIVE stress , *IRON chelates , *GLUCOSE , *IRON clusters , *IRON metabolism , *CATALASE - Abstract
Pathogens have to cope with oxidative, iron- and carbon(glucose)-limitation stresses in the human body. To understand how combined iron–carbon limitation alters oxidative stress responses, Aspergillus fumigatus was cultured in glucose–peptone or peptone containing media supplemented or not with deferiprone as an iron chelator. Changes in the transcriptome in these cultures were recorded after H2O2 treatment. Responses to oxidative stress were highly dependent on the availability of glucose and iron. Out of the 16 stress responsive antioxidative enzyme genes, only the cat2 catalase–peroxidase gene was upregulated in more than two culturing conditions. The transcriptional responses observed in iron metabolism also varied substantially in these cultures. Only extracellular siderophore production appeared important regardless of culturing conditions in oxidative stress protection, while the enhanced synthesis of Fe-S cluster proteins seemed to be crucial for oxidative stress treated iron-limited and fast growing (glucose rich) cultures. Although pathogens and host cells live together in the same place, their culturing conditions (e.g., iron availability or occurrence of oxidative stress) can be different. Therefore, inhibition of a universally important biochemical process, like Fe-S cluster assembly, may selectively inhibit the pathogen growth in vivo and represent a potential target for antifungal therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
20. Challenges of Iron Chelation in Thalassemic Children.
- Author
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Adramerina, Alkistis and Economou, Marina
- Subjects
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CHELATION , *CHELATION therapy , *IRON chelates , *IRON overload , *IRON - Abstract
Thalassemia treatment still relies on supportive care, mainly including blood transfusion and iron chelation therapy. Iron chelation is considered the main factor responsible for the marked improvement in survival rates of thalassemic patients. Hemosiderosis may be prevented if appropriate chelation therapy is offered from early childhood, with timely dose adjustments according to changing body weight and close monitoring of organ iron load. With three iron chelators currently available, the choice of appropriate chelation, either as monotherapy or combined therapy, should be individualized depending on the iron overload of target organs, patient's age, presence of adverse events and compliance issues, given known limitations related to each agent's administration. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
21. Inhibition of ferroptosis reverses heart failure with preserved ejection fraction in mice.
- Author
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Xiong, Yixiao, Liu, Xin, Jiang, Ling, Hao, Tao, Wang, Yanyan, and Li, Tao
- Subjects
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HEART failure , *VENTRICULAR ejection fraction , *ANIMAL experimentation , *PHENOTYPIC plasticity , *BLEPHAROPTOSIS , *PROTEIN-protein interactions - Abstract
Background: Heart failure with preserved ejection fraction (HFpEF) accounts for approximately 50% of heart failure cases. The molecular mechanisms by which HFpEF leads to impaired diastolic function of the heart have not been clarified, nor have the drugs that target the clinical symptoms of HFpEF patients. Methods: HFpEF chip data (GSE180065) was downloaded from the National Center for Biotechnology Information (NCBI) database. Differentially expressed genes (DEGs) were filtered by the limma package in R and processed for GO and KEGG pathway analyses. Then, ferroptosis-related genes in HFpEF were identified by taking the intersection between DEGs and ferroptosis-related genes. CytoHubba and MCODE were used to screen ferroptosis-related hub DEGs in the protein–protein interaction (PPI) network. Establishment of a mouse HFpEF model to validate the transcript levels of ferroptosis-related hub DEGs and ferroptosis-related phenotypes. Transcript levels of ferroptosis-related hub DEGs and HFpEF phenotypic changes in the hearts of HFpEF mice were further examined after the use of ferroptosis inhibitors. Results: GO and KEGG enrichment analyses suggested that the DEGs in HFpEF were significantly enriched in ferroptosis-related pathways. A total of 24 ferroptosis-related DEGs were identified between the ferroptosis gene dataset and the DEGs. The established PPI network was further analyzed by CytoHubba and MCODE modules, and 11 ferroptosis-related hub DEGs in HFpEF were obtained. In animal experiments, HFpEF mice showed significant abnormal activation of ferroptosis. The expression trends of the 11 hub DEGs associated with ferroptosis, except for Cdh1, were consistent with the results of the bioinformatics analysis. Inhibition of ferroptosis alters the transcript levels of 11 ferroptosis-related hub DEGs and ameliorates HFpEF phenotypes. Conclusions: The present study contributes to a deeper understanding of the specific mechanisms by which ferroptosis is involved in the development of HFpEF and suggests that inhibition of ferroptosis may mitigate the progression of HFpEF. In addition, eleven hub genes were recognized as potential drug binding targets. [ABSTRACT FROM AUTHOR]
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- 2024
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22. Efficacy of the iron‐chelating agent, deferiprone, in patients with Parkinson's disease: A systematic review and meta‐analysis.
- Author
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Negida, Ahmed, Hassan, Nafisa M., Aboeldahab, Heba, Zain, Youmna E., Negida, Yasmin, Cadri, Shirin, Cadri, Nivin, Cloud, Leslie J., Barrett, Matthew J., and Berman, Brian
- Subjects
- *
PARKINSON'S disease , *SUBSTANTIA nigra , *IRON , *BASAL ganglia , *RANDOMIZED controlled trials - Abstract
Introduction: Several studies have reported iron accumulation in the basal ganglia to be associated with the development of Parkinson's Disease (PD). Recently, a few trials have examined the efficacy of using the iron‐chelating agent Deferiprone (DFP) for patients with PD. We conducted this meta‐analysis to summarize and synthesize evidence from published randomized controlled trials about the efficacy of DFP for PD patients. Methods: A comprehensive literature search of four electronic databases was performed, spanning until February 2023. Relevant RCTs were selected, and their data were extracted and analyzed using the RevMan software. The primary outcome was the change in the Unified Parkinson's Disease Rating Scale (UPDRS‐III). Results: Three RCTs with 431 patients were included in this analysis. DFP did not significantly improve UPDRS‐III score compared to placebo (Standardized mean difference −0.06, 95% CI [−0.69, 0.58], low certainty evidence). However, it significantly reduced iron accumulation in the substantia nigra, putamen, and caudate as measured by T2*‐weighted MRI (with high certainty evidence). Conclusion: Current evidence does not support the use of DFP in PD patients. Future disease‐modification trials with better population selection, adjustment for concomitant medications, and long‐term follow up are recommended. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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23. Ferrochelating Treatment in Patients Affected by Neurodegeneration With Brain Iron Accumulation (NBIA)
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Dr. Gian Luca Forni, MD
- Published
- 2023
24. New Deferric Amine Compounds Efficiently Chelate Excess Iron to Treat Iron Overload Disorders and to Prevent Ferroptosis.
- Author
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Feng, Wenya, Xiao, Yuanjing, Zhao, Chuanfang, Zhang, Zhanming, Liu, Wei, Ma, Juan, Ganz, Tomas, Zhang, Junliang, and Liu, Sijin
- Subjects
deferric amine compound ,ferroptosis ,iron chelator ,iron overload ,liver injury ,Amines ,Animals ,Deferiprone ,Deferoxamine ,Dextrans ,Ferroptosis ,Hemochromatosis ,Humans ,Iron ,Iron Chelating Agents ,Iron Overload ,Mice ,Nitrogen ,Pyridones - Abstract
Excess iron accumulation occurs in organs of patients with certain genetic disorders or after repeated transfusions. No physiological mechanism is available to excrete excess iron and iron overload to promote lipid peroxidation to induce ferroptosis, thus iron chelation becomes critical for preventing ion toxicity in these patients. To date, several iron chelators have been approved for iron chelation therapy, such as deferiprone and deferoxamine, but the current iron chelators suffer from significant limitations. In this context, new agents are continuously sought. Here, a library of new deferric amine compounds (DFAs) with adjustable skeleton and flexibility is synthesized by adopting the beneficial properties of conventional chelators. After careful evaluations, compound DFA1 is found to have greater efficacy in binding iron through two molecular oxygens in the phenolic hydroxyl group and the nitrogen atom in the amine with a 2:1 stoichiometry. This compound remarkably ameliorates iron overload in diverse murine models through both oral and intravenous administration, including hemochromatosis, high iron diet-induced, and iron dextran-stimulated iron accumulation. Strikingly, this compound is found to suppress iron-induced ferroptosis by modulating the intracellular signaling that drives lipid peroxidation. This study opens a new approach for the development of iron chelators to treat iron overload.
- Published
- 2022
25. Deferiprone promoted remyelination and functional recovery through enhancement of oligodendrogenesis in experimental demyelination animal model
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Rayatpour, Atefeh, Foolad, Forough, and Javan, Mohammad
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- 2024
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26. Dual Oral Iron Chelation (DOIC) in Children with Transfusion-Dependent Beta Thalassemia: Real-World Efficacy Data
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Chadha, Amitoj Singh, Mohammad, Abaan Ul Haq Khazi, Nadakuditi, Naveen Kanth Dhãmi, Agrawal, Surbhi, Alex, Kenson Sam, Naik, Namratha S., Raj, John Michael, and Prakash, Anand
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- 2024
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27. Compassionate Use of Deferiprone in Patients With PKAN
- Published
- 2022
28. Conservative Iron Chelation as a Disease-modifying Strategy in Amyotrophic Lateral Sclerosis (FAIR-ALS II)
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Ministry of Health, France
- Published
- 2022
29. Conservative Iron Chelation as a Disease-modifying Strategy in Parkinson's Disease (FAIRPARKII)
- Author
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European Commission and ApoPharma
- Published
- 2022
30. Application of validated UV–Vis spectrophotometry-colorimetric methods for specific quantification of deferiprone in the development of iron-responsive nanoparticle loaded into dissolving microneedle
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Maharani, Sitti Nur Khadijah, Hidayat, Muh. Taufik, Ramadhany, Indianty Dwi, Khairani, Nur Izzah, Rahman, Nur Annisa, and Permana, Andi Dian
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- 2024
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31. COST EFFECTIVENESS ANALYSIS OF ORAL IRON CHELATING DRUGS BETWEEN DEFERIPRONE AND DEFERASIROX IN THALASEMIA MAJOR PATIENTS AT BHAYANGKARA SETUKPA LEMDIKLAT POLRI TK.II HOSPITAL.
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Abidin, Rizal Mustia, Suwantika, Auliya A., and Pradipta, Ivan S.
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IRON chelates ,COST effectiveness ,COST analysis ,DEFERASIROX ,BETA-Thalassemia - Abstract
Thalassemia is a blood disorder that results from decreased or lost synthesis of one or more globin chains. Thalassemia major as a red blood cell disorder requires high costs because it requires blood transfusions and the use of iron chelation drugs throughout the patient's life. This study aims to analyze the cost and effectiveness of oral iron chelation drugs such as deferasirox and deferiprone in patients with Thalassemia major at Setukpa Lemdiklat Polri Tk--II Hospital in 2023. Data was collected retrospectively using total sampling from patient medical records and hospital information system data. Based on the results of this study, the average total cost per treatment for thalassemia major patients who used deferasirox (IDR 52,969,775,-) was more expensive than deferiprone (IDR 49,407,613,-). The effectiveness of deferasirox (1,364 ng/mL) was bigger than that of deferiprone (1,210 ng/mL). The cost-effectiveness ratio of deferasirox (IDR 38,834,-) was lower than that of deferiprone (IDR 40,833,-). To change the drug from deferiprone to deferasirox requires an additional cost of IDR 23,130 per one additional unit. From the average costeffectiveness ratio, it can be concluded that deferasirox is more cost-effective than deferiprone. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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32. COST-EFFECTIVENESS OF ORAL IRON CHELATION IN PATIENTS WITH THALASSEMIA MAJOR: A SYSTEMATIC REVIEW.
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Abidin, Rizal Mustia, Puspita, Falerina, Dewi, Christiyanti, and Hanggoro, Fajar
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BETA-Thalassemia ,ECONOMIC databases ,CHELATION ,COST effectiveness ,ERYTHROCYTES ,IRON - Abstract
Thalassemia major, as a red blood cell disorder that is passed from both parents to their children, requires high costs and the use of iron chelation drugs throughout the patient's life. Pharmacoeconomics studies in patients with thalassemia major needs to be conducted to determine the efficiency and effectiveness of selecting oral iron chelation drugs. This study aims to analyze the cost and cost-effectiveness of using oral iron chelation drugs such as deferasirox and deferiprone. This systematic review was conducted from Pubmed and Scopus, to identify the cost-effectiveness of deferasirox and deferiprone. Eight studies met the inclusion criteria for the review. farthermor selected the papers, extracted the data, and assessed the methodological quality of the included documents. In brief, deferasirox is cost-effective than deferiprone. Moreover, the cost-effectiveness is not an absolute issue when in different countries (regions) the results are opposite for other countries (regions). As a result, the local/national context had a substantial influence on the results of the pharmacoeconomic evaluation. From the average cost-effectiveness ratio, it can be concluded that deferasirox is more cost-effective than deferiprone. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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33. Combination chelation therapy.
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Aydinok, Yesim
- Subjects
- *
CHELATION therapy , *IRON overload , *IRON chelates , *IRON , *CHELATION - Abstract
Combination chelation therapies are considered in transfusion‐dependent thalassemia patients for whom monotherapy regimens have failed to achieve iron balance or intensification of iron chelation therapy is required for the rapid reduction of excess iron to avoid permanent organ damage. Combination chelation may provide a more flexible approach for individualizing chelation therapy, thereby improving tolerability, adherence, and quality of life. In principle, iron chelators can be combined with an infinite number of dosing regimens; these involve simultaneous or sequential exposure to the chelators on the same day or alternating the drugs on different days. Clinical studies have established the safety and efficacy of chelation combinations. However, real‐life data with combination therapies indicate the significance of compliance for a meaningful reduction in iron overload compared to monotherapies. [ABSTRACT FROM AUTHOR]
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- 2023
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34. On the Role of Iron in Idiopathic Parkinson's Disease.
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Huenchuguala, Sandro and Segura-Aguilar, Juan
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PARKINSON'S disease ,IRON ores ,IRON in the body ,IRON chelates ,IRON ,POSTMORTEM changes - Abstract
The transition metal characteristics of iron allow it to play a fundamental role in several essential aspects of human life such as the transport of oxygen through hemoglobin or the transport of electrons in the mitochondrial respiratory chain coupled to the synthesis of ATP. However, an excess or deficiency of iron is related to certain pathologies. The maintenance of iron homeostasis is essential to avoid certain pathologies related to iron excess or deficiency. The existence of iron deposits in postmortem tissues of Parkinson's patients has been interpreted as evidence that iron plays a fundamental role in the degenerative process of the nigrostriatal system in this disease. The use of iron chelators has been successful in the treatment of diseases such as transfusion-dependent thalassemia and pantothenate kinase-associated neurodegeneration. However, a clinical study with the iron chelator deferiprone in patients with Parkinson's disease has not shown positive effects but rather worsened clinical symptoms. This suggests that iron may not play a role in the degenerative process of Parkinson's disease. [ABSTRACT FROM AUTHOR]
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- 2023
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35. Chitogel with deferiprone following endoscopic sinus surgery: improved wound healing and microbiome
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Anna Megow, George Bouras, Yazeed Alsuliman, Clare Cooksley, Erich Vyskocil, William Murphy, Sarah Vreugde, and Peter-John Wormald
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endoscopic sinus surgery ,chronic rhinosinusitis (CRS) ,wound healing ,microbiome ,chitosan–dextran gel ,deferiprone ,Surgery ,RD1-811 - Abstract
BackgroundAdhesion formation, sinus ostial narrowing, and presence of pathogenic bacteria are associated with poor outcomes following endoscopic sinus surgery (ESS) for chronic rhinosinusitis. Chitogel has been shown to improve wound healing, restore a healthier microbiome, and reduce post-operative infections post ESS. Deferiprone has antibacterial properties and has been shown to reduce adhesion formation. The aim of the study was to assess whether the addition of low concentration deferiprone to Chitogel further improves surgical outcomes following ESS compared with Chitogel alone.MethodsIn this double-blinded trial, 45 patients undergoing ESS were prospectively recruited. At the end of the surgery, patients were randomised to receive Chitogel alone, Chitogel with 1 mM of deferiprone, or Chitogel with 5 mM of deferiprone to one side of the sinuses (allowing the other side to serve as control). Patients underwent routine follow-ups with symptom questionnaires and nasoendoscopies performed at 2, 6, and 12 weeks post-operatively. Sinus ostial measurements, microbiology, and microbiome swabs from bilateral middle meatuses were collected intraoperatively and at 12 weeks post-operatively.ResultsA significant improvement in the endoscopic appearance of the sinuses and frontal ostial patency was noted at 12 weeks post-operatively (p
- Published
- 2024
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36. Deferiprone–resveratrol hybrid attenuates iron accumulation, oxidative stress, and antioxidant defenses in iron-loaded human Huh7 hepatic cells
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Jin Li, Pimpisid Koonyosying, Woranontee Korsieporn, Narisara Paradee, Nuntouchaporn Hutachok, Honghong Xu, Yongmin Ma, Hataichanok Chuljerm, and Somdet Srichairatanakool
- Subjects
iron chelator ,deferiprone ,resveratrol ,antioxidant ,hepatoprotective ,Biology (General) ,QH301-705.5 - Abstract
Chronic liver diseases are complications of thalassemia with iron overload. Iron chelators are required to remove excessive iron, and antioxidants are supplemented to diminish harmful reactive oxygen species (ROS), purposing to ameliorate oxidative liver damage and dysfunctions. The deferiprone–resveratrol hybrid (DFP–RVT) is a synthetic iron chelator possessing anti-β-amyloid peptide aggregation, anti-malarial activity, and hepatoprotection in plasmodium-infected mice. The study focuses on investigating the antioxidant, cytotoxicity, iron-chelating, anti-lipid peroxidation, and antioxidant defense properties of DFP–RVT in iron-loaded human hepatocellular carcinoma (Huh7) cells. In the findings, DFP–RVT dose dependently bound Fe(II) and Fe(III) and exerted stronger ABTS•- and DPPH•-scavenging (IC50 = 8.0 and 164 μM, respectively) and anti-RBC hemolytic activities (IC50 = 640 μM) than DFP but weaker than RVT (p < 0.01). DFP–RVT was neither toxic to Huh7 cells nor PBMCs. In addition, DFP–RVT diminished the level of redox-active iron (p < 0.01) and decreased the non-heme iron content (p < 0.01) in iron-loaded Huh7 cells effectively when compared without treatment in the order of DFP–RVT > RVT ∼ DFP treatments (50 µM each). Moreover, the compound decreased levels of hepatic ROS in a dose-dependent manner and the level of malondialdehyde, which was stronger than DFP but weaker than RVT. Furthermore, DFP–RVT restored the decrease in the GSH content and GPX and SOD activities (p < 0.01) in iron-loaded Huh7 cells in the dose-dependent manner, consistently in the order of RVT > DFP–RVT > DFP. Thus, the DFP–RVT hybrid possesses potent iron chelation, antioxidation, anti-lipid peroxidation, and antioxidant defense against oxidative liver damage under iron overload.
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- 2024
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37. Corrigendum: Infratentorial superficial siderosis: report of six cases and review of the literature
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Lixia Deng, Yi Lin, Yu Lin, and Weibin Huang
- Subjects
infratentorial superficial siderosis ,magnetic resonance imaging ,dural tear ,deferiprone ,T2-weighted imaging ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Published
- 2024
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38. Deferiprone: new environmental perspectives. Insights into its sequestering ability vs. different metal cations
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Anna Irto, Francesco Crea, Marco Milone, Giuseppe Gattuso, Clemente Bretti, Concetta De Stefano, and Rosalia Maria Cigala
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Environmental chemistry ,Deferiprone ,Chelating agents ,Speciation ,Lead ,Cadmium ,Environmental pollution ,TD172-193.5 ,Environmental sciences ,GE1-350 - Abstract
Deferiprone, generally, is considered an important chelating agent for Fe3+ overload. From a literature data analysis, a lack of information on the interaction of this molecule toward a series of metal cations emerged, inducing to fill out the topic. The complexing ability of deferiprone toward Ca2+, Mg2+, Cd2+ and Pb2+ was studied by potentiometry and 1H NMR spectroscopy, in KCl aqueous solutions at different ionic strength values (0.1 ≤ I/mol dm−3 ≤ 1.0) and T = 298.15 K. The same speciation model featured by the ML, ML2, ML3 and ML(OH) (M = metal and L = deferiprone or DFP) species was obtained for Cd2+ and Pb2+; the formation constants calculated at infinite dilution are: logTβ = 7.23±0.02, 12.47±0.03, 16.70±0.04, and −2.53±0.04, respectively for Cd2+ and 9.91±0.01, 15.99±0.02, 19.93±0.05 and 0.99±0.02 for Pb2+. Only two species, namely ML and ML2, were determined for Ca2+ and Mg2+, whose formation constants at infinite dilution are respectively: 3.72±0.01 and 6.50±0.02, for the first one, 5.31±0.01 and 9.58±0.01, for the second. The ligand sequestering ability and affinity toward M2+ were evaluated by determining the pL0.5 and pM parameters at different pHs and ionic strengths. The results suggest that deferiprone has the best complexing and sequestering ability toward Pb2+, followed by Cd2+, Mg2+ and Ca2+, respectively. 1H NMR studies confirmed the DFP affinity for Cd2+ and Pb2+, and in combination with DFT calculations showed that metal cations are bound to the hydroxo-oxo moiety of the pyridinone ring. The data reported in this study provide information on the possible employment of a small molecule like deferiprone, as a chelating and sequestering agent for Pb2+ accumulation or overload from environmental and biological matrices.
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- 2024
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39. Iron Chelation in the Prevention of Secondary Degeneration After Stroke (CHEL-IC)
- Published
- 2022
40. Comparison of oral iron chelators in the management of transfusion-dependent β-thalassemia major based on serum ferritin and liver enzymes [version 2; peer review: 1 approved, 1 approved with reservations]
- Author
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Sulaiman Yusuf, Heru Noviat Herdata, Eka Destianti Edward, and Khairunnisa Khairunnisa
- Subjects
Brief Report ,Articles ,Alanine transaminase ,aspartate transaminase ,iron overload ,deferiprone ,deferasirox - Abstract
Background Excess iron deriving from a chronic transfusion and dietary intake increases the risk for cardiac complications in β-thalassemia major patients. Deferiprone and deferasirox are commonly prescribed to thalassemic patients who are at risk of iron overload. This study aimed to compare the performance and toxicity of deferiprone and deferasirox in β-thalassemia major patients. Methods A cross-sectional observation was performed on 102 patients with β-thalassemia major. Serum ferritin along with total, indirect, and direct bilirubin levels were measured. Levels of liver enzymes, transaminase (ALT), and aspartate transaminase (AST), were also determined. Ferritin correlations with serum ALT, AST, and total bilirubin were constructed based on Spearman’s rank correlation. Statistical differences based on the serum parameters were analyzed between deferiprone and deferasirox groups. The differences of iron chelators’ effects between those receiving short-term (≤7 years) and long-term (>7 years) blood transfusion were also analyzed. Results The averaged levels of bilirubin, ALT, AST, and ferritin were found to be high. Ferritin was positively correlated with ALT (r=0.508 and pp=0.776). However, higher total bilirubin and ALT were observed in the deferasirox group than in the deferiprone group ( p=0.001 and 0.022, respectively). Total ( ppp=0.015) were significantly higher in patients with long-term transfusions than those receiving short-term transfusions. Higher ferritin was found with a statistical significance of p=0.008 in the long-term transfusions group. Conclusions Ferritin is high in people with transfusion-dependent β-thalassemia major and positively correlated with ALT and AST. Deferasirox might pose a higher risk of developing hepatic injury as compared with deferiprone. Yet, no significant change of deferasirox efficacy (based on ferritin level) was found between those receiving short-term and long-term transfusions.
- Published
- 2023
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41. One-step determination of total iron using deferiprone or kojic acid as colorimetric reagents
- Author
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Rosita Cappai, Alessandra Fantasia, Andrea Melchior, Guido Crisponi, and Valeria M. Nurchi
- Subjects
Iron ,Colorimetric reagent ,Deferiprone ,Kojic acid ,Spectrophotometry ,Chemistry ,QD1-999 - Abstract
The role of iron, one of the most common metals in the environment, is fundamental in many biological and geochemical processes, which determine its availability in the two main oxidation states Fe2+ and Fe3+. Its relevance in the environment, industrial applications, and human physiology, as well as in many other fields has constantly encouraged the development of analytical techniques for its accurate determination. Spectrophotometric methods are those most frequently applied for iron determination in real samples, with specific reagents for the two existing oxidation state right now. In the present work, two low-cost, non-toxic, colorimetric reagents are proposed: deferiprone and kojic acid. These compounds present peculiar features, in particular the formation of 1:3 complexes with Fe3+ of extremely high stability and absorptivity in a wide operative pH range. In this study, we show that both reagents can be used to measure the total iron content. Actually, the extremely low redox potential characterizing the FeL3 complexes permits to determine the total concentration of iron independently from the starting oxidation state, and assures the complete oxidation in presence of oxygen of any amount of Fe2+ to Fe3+ complexes. These features constitute a novelty in the analytical determination of total iron not requiring any pretreatment of the sample, contrary to the methods in use, devoted either to Fe3+ or to Fe2+, necessitating awkward and error generating oxidative or reductive processes. The analytical performance of the proposed spectrophotometric method has been evaluated for the full compliance with the Lambert-Beer law, the operative range of iron concentration, the influence of pH, and the interfering effects of other metal ions. Finally, it has been validated in terms of LoD, LoQ, linearity, precision, and trueness, and has been tested on total iron determination in natural water certified material and in two biological reference materials, human urine and serum.
- Published
- 2024
- Full Text
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42. Favipiravir vs. Deferiprone: Tautomeric, photophysical, in vitro biological studies, and binding interactions with SARS-Cov-2-MPro/ACE2
- Author
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Nikolay T. Tzvetkov, Martina I. Peeva, Maya G. Georgieva, Vera Deneva, Aneliya A. Balacheva, Ivan P. Bogdanov, Maria Ponticelli, Luigi Milella, Kiril Kirilov, Maima Matin, Hans-Georg Stammler, Atanas G. Atanasov, and Liudmil Antonov
- Subjects
Favipiravir ,Deferiprone ,Tautomer-based drug design ,COVID-19 ,Molecular modelling ,Tautomerism ,Biotechnology ,TP248.13-248.65 - Abstract
Coronavirus disease 2019 (COVID-19) still remains the most disastrous infection continuously affecting millions of people worldwide. Herein, we performed a comparative study between the anti-influenza drug favipiravir (FAV) and the anti-thalassemia drug deferiprone (DFP) in order to examine their potential as basic scaffolds for the generation of most effective and structurally novel antivirals. To conduct the initial molecular modelling and virtual screening steps, our recently proposed single crystal X-ray diffraction (SCXRD)/HYdrogen DEssolvation (HYDE) technology platform has been used. This platform allows molecular design, interactive prioritization and virtual evaluation of newly designed molecules, simultaneously affecting two COVID-related targets, including angiotensin-converting enzyme 2 (ACE2) as a host-cellular receptor (host-based approach) and the main protease (Mpro) enzyme of the spike glycoprotein of SARS-Cov-2 (virus-based approach). Based on the molecular docking results, DFP has shown higher binding affinity (Ki HYDE values) over FAV towards both biological targets. The tautomeric, physicochemical, and biological properties of FAV and DFP have been studied both experimentally and theoretically using molecular spectroscopy (UV–VIS absorption), parallel artificial membrane permeability assay, and cell biology (PAMPA and MTT assay), as well as DFT quantum chemical calculations. According to the obtained results, the enol tautomers of both compounds are considerably more stable in different organic solvents. However, the keto tautomer of FAV was estimated to be most preferable under physiological conditions, which is in good agreement with the molecular docking studies. The isolated crystal structure of DFP is in an excellent agreement with the computation in respect of the most stable tautomer. Combined single X-ray/molecular modeling studies including HYDE analyses provided not only insights into the protein–ligand interactions within the binding site of SARS-Cov-2-ACE2 and SARS-Cov-2-Mpro, but also a valuable information regarding the most stable enol tautomeric form of DFP that contributes to its estimated higher potency against these targets.
- Published
- 2024
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43. Deferiprone to Delay Dementia (The 3D Study)
- Author
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The Florey Institute of Neuroscience and Mental Health
- Published
- 2022
44. Comparison of oral iron chelators in the management of transfusion-dependent β-thalassemia major based on serum ferritin and liver enzymes [version 2; peer review: 2 approved]
- Author
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Khairunnisa Khairunnisa, Heru Noviat Herdata, Eka Destianti Edward, and Sulaiman Yusuf
- Subjects
Alanine transaminase ,aspartate transaminase ,iron overload ,deferiprone ,deferasirox ,eng ,Medicine ,Science - Abstract
Background Excess iron deriving from a chronic transfusion and dietary intake increases the risk for cardiac complications in β-thalassemia major patients. Deferiprone and deferasirox are commonly prescribed to thalassemic patients who are at risk of iron overload. This study aimed to compare the performance and toxicity of deferiprone and deferasirox in β-thalassemia major patients. Methods A cross-sectional observation was performed on 102 patients with β-thalassemia major. Serum ferritin along with total, indirect, and direct bilirubin levels were measured. Levels of liver enzymes, transaminase (ALT), and aspartate transaminase (AST), were also determined. Ferritin correlations with serum ALT, AST, and total bilirubin were constructed based on Spearman’s rank correlation. Statistical differences based on the serum parameters were analyzed between deferiprone and deferasirox groups. The differences of iron chelators’ effects between those receiving short-term (≤7 years) and long-term (>7 years) blood transfusion were also analyzed. Results The averaged levels of bilirubin, ALT, AST, and ferritin were found to be high. Ferritin was positively correlated with ALT (r=0.508 and p
- Published
- 2023
- Full Text
- View/download PDF
45. Iron chelation improves ineffective erythropoiesis and iron overload in myelodysplastic syndrome mice
- Author
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Wenbin An, Maria Feola, Maayan Levy, Srinivas Aluri, Marc Ruiz-Martinez, Ashwin Sridharan, Eitan Fibach, Xiaofan Zhu, Amit Verma, and Yelena Ginzburg
- Subjects
myelodysplastic dyndrome ,deferiprone ,ineffective erythropoiesis ,iron trafficking ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
Myelodysplastic syndrome (MDS) is a heterogeneous group of bone marrow stem cell disorders characterized by ineffective hematopoiesis and cytopenias, most commonly anemia. Red cell transfusion therapy for anemia in MDS results in iron overload, correlating with reduced overall survival. Whether the treatment of iron overload benefits MDS patients remains controversial. We evaluate underlying iron-related pathophysiology and the effect of iron chelation using deferiprone on erythropoiesis in NUP98-HOXD13 transgenic mice, a highly penetrant well-established MDS mouse model. Our results characterize an iron overload phenotype with aberrant erythropoiesis in these mice which was reversed by deferiprone-treatment. Serum erythropoietin levels decreased while erythroblast erythropoietin receptor expression increased in deferiprone-treated MDS mice. We demonstrate, for the first time, normalized expression of the iron chaperones Pcbp1 and Ncoa4 and increased ferritin stores in late-stage erythroblasts from deferiprone-treated MDS mice, evidence of aberrant iron trafficking in MDS erythroblasts. Importantly, erythroblast ferritin is increased in response to deferiprone, correlating with decreased erythroblast ROS. Finally, we confirmed increased expression of genes involved in iron uptake, sensing, and trafficking in stem and progenitor cells from MDS patients. Taken together, our findings provide evidence that erythroblast-specific iron metabolism is a novel potential therapeutic target to reverse ineffective erythropoiesis in MDS.
- Published
- 2023
- Full Text
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46. Vectorization via Siderophores Increases Antibacterial Activity of K(RW)3 Peptides against Pseudomonas aeruginosa.
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Olshvang, Evgenia, Fritsch, Sarah, Scholtyssek, Oliver C., Schalk, Isabelle J., and Metzler‐Nolte, Nils
- Subjects
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SIDEROPHORES , *ANTIMICROBIAL peptides , *ANTIBACTERIAL agents , *PSEUDOMONAS aeruginosa , *IRON chelates , *DEFEROXAMINE - Abstract
A series of new conjugates comprised from a small synthetic antimicrobial peptide (AMP) and a siderophore‐type vector component was designed and tested for activity on P. aeruginosa PAO1 and several genetically modified strains. As AMP, the well‐established arginine‐tryptophane combination K(RW)3 (P1) was chosen with an added lysine for siderophore attachment. This peptide is easy to prepare, modify, and possesses good anti‐bacterial activity. On the vector part, we examined several moieties: (i) the natural siderophore deferoxamine (DFO); (ii) bidentate iron chelators based on the hydroxamate building block (4 a–c) ; (iii) the non‐siderophore chelators deferasirox (DFX) and deferiprone‐carboxylate (DFP‐COOH). All conjugates were prepared by solid phase synthesis techniques and fully characterized by HPLC and mass spectrometry (including HR‐MS). 55Fe uptake assays indicate a receptor‐mediated uptake for 4 a–c, DFP‐COOH and DFO, which is dependent on the outer membrane transporter FoxA in the case of DFO. All conjugates showed increased antibacterial activity against P. aeruginosa compared to the parent peptide P1 alone when investigated in iron‐depleted medium. MIC values were as low as 2 μM (for P1‐DFP) on wild type P. aeruginosa. The activity of P1‐DFO and P1‐DFP was even better on genetically mutated strains unable to produce siderophores (down to 0.5 μM). Although the DFX vector on its own was not able to transport iron inside the bacterial cell as shown by 55Fe uptake studies, the P1‐DFX conjugate had excellent antibacterial activity compared to P1 (2 μM, and as low as 0.25 μM on a receptor‐deficient strain unable to produce siderophores), suggesting that the conjugates were indeed recognized and internalized by an (unknown) transporter. Control experiments with an equimolar mixture of P1 and DFX confirm that the observed activity is intrinsic to vectorization. This work thus demonstrates the power of linking small AMPs covalently to siderophores for a new class of Trojan Horse antibiotics, with P1‐DFP and P1‐DFX being the most potent conjugates. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
47. Synthesis of a New Nanocomposite Based on Natural Asphalt and Its Application as a High-Performance and Eco-friendly Platform for the Electrochemical Determination of Deferiprone.
- Author
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Farokhi, Somayeh, Roushani, Mahmoud, Hosseini, Hadi, Zalpour, Neda, and Soleiman-Beigi, Mohammad
- Abstract
Designing efficient and economical nano-catalysts in the development of electrochemical sensors has been a constant challenge. The design of core–shell nanoarrays using natural asphalt (NA) as the core has not been found in reports. In this report, for the first time, flower-like nanostructures were synthesized by joining nickel–cobalt double hydroxide nanosheets (NiCo-LDH NSs) on NA as a precursor. The synthesis of flower-like nanostructures, abbreviated as NA@NiCo-LDH NSs, was done by an easy and one-step hydrothermal method. NA has characteristics such as availability, cost-effectiveness, high surface area due to its porous structure, and good interaction with the surface of carbon electrodes due to its carbonaceous nature. In addition, the growth of NiCo-LDH NSs on the NA leads to the improvement of electrocatalytic properties, the creation of a larger specific surface area, available active sites, and an increase of contact between analyte and nanostructures. The performance of synthetic nanostructures in the electrochemical determination of deferiprone (DFN) was evaluated satisfactorily. DFN is the first oral iron chelator and the first drug for thalassemia patient treatment. This strategy has some advantages such as cost-effectiveness, portability, good linear range (0.5–2500 µM), and low detection limit (0.19 µM) in the DFN determination. The proposed strategy can be a way to develop new nanomaterials derived from NA with green chemistry in mind. In addition, it can be a way to enter NA-based nanomaterials into other applications. Flower-like nanostructures based on natural asphalt (NA) coated with nickel-cobalt double hydroxide nanosheets (NiCo-LDH NSs) have been synthesized and their application as a high-performance platform for the electrocatalytic oxidation of deferiprone has been studied. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
48. RP-HPLC method development for simultaneous estimation of oral iron chelator deferiprone and its related impurity
- Author
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Sutar, Shubhangi, Patil, Puja, Marchande, Diptee, Patil, Sachinkumar, Bandgar, Sandip, and Kumbhar, Ravindra
- Published
- 2023
- Full Text
- View/download PDF
49. Oxidative stress and renal function in pediatric patients with beta thalassemia major (β-TM) receiving deferiprone and deferasirox: A cross-sectional, single center study
- Author
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Wijaya, Andreas Budi, Marhaeni, Wulandewi, Triawanti, Devi, Wivina Riza, Saputra, Maulana, and Rahman, Galih
- Published
- 2023
- Full Text
- View/download PDF
50. Clinical Curative Effect Evaluation Study of Treatment of Oral Deferiprone Tablets in Aceruloplasminaemia Patients
- Author
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Wan-Jin Chen, Professor
- Published
- 2021
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