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CNS Neuroscience & Therapeutics Feb 2024Several 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... (Meta-Analysis)
Meta-Analysis Review
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.
Topics: Humans; Deferiprone; Parkinson Disease; Iron Chelating Agents; Iron; Substantia Nigra
PubMed: 38334258
DOI: 10.1111/cns.14607 -
Chitogel with deferiprone following endoscopic sinus surgery: improved wound healing and microbiome.Frontiers in Surgery 2024Adhesion formation, sinus ostial narrowing, and presence of pathogenic bacteria are associated with poor outcomes following endoscopic sinus surgery (ESS) for chronic...
BACKGROUND
Adhesion 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.
METHODS
In 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.
RESULTS
A significant improvement in the endoscopic appearance of the sinuses and frontal ostial patency was noted at 12 weeks post-operatively ( < 0.05) in all three treatment groups compared with the control. There was no significant difference noted between patients who received Chitogel alone and those who received Chitogel with 1 or 5 mM deferiprone.
CONCLUSION
Chitogel alone, Chitogel with 1 mM deferiprone, and Chitogel with 5 mM deferiprone used following ESS led to a significant improvement in endoscopic appearance of the sinuses and frontal ostial preservation at 12 weeks post-operatively. No significant difference was found with the addition of deferiprone to Chitogel.
PubMed: 38638142
DOI: 10.3389/fsurg.2024.1338209 -
Biomedicines Nov 2023The 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... (Review)
Review
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.
PubMed: 38002094
DOI: 10.3390/biomedicines11113094 -
Ecotoxicology and Environmental Safety Mar 2024Deferiprone, generally, is considered an important chelating agent for Fe overload. From a literature data analysis, a lack of information on the interaction of this...
Deferiprone, generally, is considered an important chelating agent for Fe 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 Ca, Mg, Cd and Pb was studied by potentiometry and H NMR spectroscopy, in KCl aqueous solutions at different ionic strength values (0.1 ≤ I/mol dm ≤ 1.0) and T = 298.15 K. The same speciation model featured by the ML, ML, ML and ML(OH) (M = metal and L = deferiprone or DFP) species was obtained for Cd and Pb; the formation constants calculated at infinite dilution are: logβ = 7.23±0.02, 12.47±0.03, 16.70±0.04, and -2.53±0.04, respectively for Cd and 9.91±0.01, 15.99±0.02, 19.93±0.05 and 0.99±0.02 for Pb. Only two species, namely ML and ML, were determined for Ca and Mg, 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 M were evaluated by determining the pL and pM parameters at different pHs and ionic strengths. The results suggest that deferiprone has the best complexing and sequestering ability toward Pb, followed by Cd, Mg and Ca, respectively. H NMR studies confirmed the DFP affinity for Cd and Pb, 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 Pb accumulation or overload from environmental and biological matrices.
Topics: Deferiprone; Cadmium; Lead; Cations; Models, Theoretical; Chelating Agents
PubMed: 38295733
DOI: 10.1016/j.ecoenv.2024.116027 -
Antibiotics (Basel, Switzerland) Jul 2023Metal ions, including Fe, affect the target site binding of some antibiotics and control the porin- and siderophore-mediated uptake of antibiotics. Amphiphilic...
Metal ions, including Fe, affect the target site binding of some antibiotics and control the porin- and siderophore-mediated uptake of antibiotics. Amphiphilic tobramycins are an emerging class of antibiotic potentiators capable of synergizing with multiple classes of antibiotics against Gram-negative bacteria, including . To study how the antibiotic-potentiating effect of amphiphilic tobramycins is affected by the presence of intermolecular iron chelators, we conjugated the FDA-approved iron chelator deferiprone (DEF) to tobramycin (TOB). Three TOB-DEF conjugates differing in the length of the carbon tether were prepared and tested for antibacterial activity and synergistic relationships with a panel of antibiotics against clinical isolates of . While all TOB-DEF conjugates were inactive against , the TOB-DEF conjugates strongly synergized with outer-membrane-impermeable antibiotics, such as novobiocin and rifampicin. Among the three TOB-DEF conjugates, containing a C tether showed a remarkable and selective potentiating effect to improve the susceptibility of multidrug-resistant isolates to tetracyclines when compared with other antibiotics. However, the antibacterial activity and antibiotic-potentiating effect of the optimized conjugate was not enhanced under iron-depleted conditions, indicating that the function of the antibiotic potentiator is not affected by the Fe concentration.
PubMed: 37627681
DOI: 10.3390/antibiotics12081261 -
Medicine Oct 2023This century has seen a revolution the management of beta-thalassemia major. Over a 12-year period to 2016, we aimed to analyze the benefits of such advances. In 209...
This century has seen a revolution the management of beta-thalassemia major. Over a 12-year period to 2016, we aimed to analyze the benefits of such advances. In 209 patients, independent of the chelation regimen, ferritin, cardiac T2* and liver iron concentration changes were evaluated. We defined chelation success (ChS) as no iron load in the heart and acceptable levels in the liver. Over 3 early magnetic resonance imagings, the same parameters were assessed in 2 subgroups, the only 2 that had sufficient patients continuing on 1 regimen and for a significant period of time, 1 on deferrioxamine (low iron load patients n = 41, Group A) and 1 on deferoxamine-deferiprone (iron overloaded n = 60, Group B). Finally, 28 deaths and causes were compared to those of an earlier period. The 209 patients significantly optimized those indices, while the number of patients with chelation success, increased from 6% to 51% (P < .0001). In group A, ChS after about 8 years increased from 21 to 46% (P = .006), while in Group B, from 0% to 60% (P < .001) after about 7 years. Deaths over the 2 periods showed significant reduction. Combined clearance of cardiac and liver iron (ChS) is feasible and should become the new target for all patients. This requires, serial magnetic resonance imagings and often prolonged intensified chelation for patients.
Topics: Humans; Iron Chelating Agents; beta-Thalassemia; Deferoxamine; Deferiprone; Chelation Therapy; Pyridones; Iron; Liver
PubMed: 37832083
DOI: 10.1097/MD.0000000000035455 -
Frontiers in Neuroscience 2024To investigate the etiology, clinical manifestations, imaging features, and treatment of patients with infratentorial superficial siderosis (iSS), enhance clinicians'...
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.
PubMed: 38435058
DOI: 10.3389/fnins.2024.1373358 -
Tuberculosis (Edinburgh, Scotland) Sep 2023Non-Tuberculous Mycobacterial Pulmonary Disease (NTM-PD) caused by Mycobacterium abscessus is a frequent complication in patients with cystic fibrosis (CF) that worsens...
Non-Tuberculous Mycobacterial Pulmonary Disease (NTM-PD) caused by Mycobacterium abscessus is a frequent complication in patients with cystic fibrosis (CF) that worsens lung function over time. Currently, there is no cure for NTM-PD, hence new therapies are urgently required. Disrupting bacterial iron uptake pathways using gallium-protoporphyrin (IX) (GaPP), a heme analog, has been proposed as a novel antibacterial approach to tackle multi-drug resistant M. abscessus. However, the antibacterial activity of GaPP has been tested only in iron-deficient media, which cannot accurately mirror the potential activity in vivo. Herein, we investigated the potential synergistic activity between GaPP and the iron-chelating agent deferiprone (Def) in regular media against M. abscessus-infected macrophages. The safety of the treatment was assessed in vitro using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in Nuli-1 and THP-1 cell lines. Def-GaPP had synergistic activity against M. abscessus-infected macrophages where 10 mM-12.5 mg/L of Def-GaPP reduced the viability by up to 0.9 log. Furthermore, Def-GaPP showed no cytotoxicity to Nuli-1 and THP-1 cell lines at the effective antibacterial concentrations (10 mM-12.5 mg/L) of Def- GaPP. These data encourage future investigation of Def-GaPP as a novel antimicrobial against NTM-PD.
Topics: Deferiprone; Gallium; Protoporphyrins; Humans; Mycobacterium abscessus; Mycobacterium Infections, Nontuberculous; Anti-Bacterial Agents; Iron Chelating Agents; THP-1 Cells; Drug Synergism
PubMed: 37506532
DOI: 10.1016/j.tube.2023.102390 -
Frontiers in Molecular Biosciences 2024Chronic liver diseases are complications of thalassemia with iron overload. Iron chelators are required to remove excessive iron, and antioxidants are supplemented to...
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 (IC = 8.0 and 164 μM, respectively) and anti-RBC hemolytic activities (IC = 640 μM) than DFP but weaker than RVT ( < 0.01). DFP-RVT was neither toxic to Huh7 cells nor PBMCs. In addition, DFP-RVT diminished the level of redox-active iron ( < 0.01) and decreased the non-heme iron content ( < 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 ( < 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.
PubMed: 38572444
DOI: 10.3389/fmolb.2024.1364261 -
BioMed Research International 2023The primary aim of this study was to evaluate the prevalence of iron overload and the real-world clinical effectiveness of the iron chelation therapies (ICTs) in Syrian... (Observational Study)
Observational Study
OBJECTIVES
The primary aim of this study was to evaluate the prevalence of iron overload and the real-world clinical effectiveness of the iron chelation therapies (ICTs) in Syrian patients with transfusion-dependent beta thalassemia major (BTM) prior to and during the ongoing Syrian conflict.
METHODS
This single-center, two-stage observational study was conducted at Homs National Thalassemia Center (HNTC) prior to (2009) and during (2019) the armed conflict. The prevalence and the severity of iron overload, as well as the effectiveness of four iron chelation regimens, were assessed using serum ferritin (SF) concentrations as a means of monitoring in two cohorts of BTM patients receiving deferoxamine (DFO), deferiprone (DFP), deferasirox (DFX), or a combination of DFO and DFP therapy in both years. Statistical analyses encompassed one-way ANOVA, Kruskal-Wallis, Mann-Whitney , and chi-square (2) tests for the comparisons of the variables and the frequencies between the two cohorts and subgroups.
RESULTS
We included all eligible BTM patients at HNTC in 2009 ( = 205) and 2019 ( = 172). Only 84 patients from the 2009 cohort were accessible in 2019. Our findings revealed that 98% and 89% of the patients had iron overload ( ≥ 1500 ng/mL) and comparable elevated median SF concentrations (3868 and 3757 ng/mL) in 2009 and 2019, respectively ( = 0.275). Furthermore, patients on DFO demonstrated the poorest control of iron overload and the highest SF concentrations (4319 and 5586 ng/mL), whereas those on DFX achieved superior outcomes and the lowest SF concentrations (3355 and 2152 ng/mL) in both years. Twenty-six patients from the 2019 cohort received no ICT for six years (from 2012 to 2018) and experienced extremely severe iron overload with SF levels ranging between 4481 and 16,000 ng/mL.
CONCLUSIONS
Our findings prove a high prevalence of iron overload and suboptimal chelation outcomes in Syrian BTM patients, both prior to and during the ongoing armed conflict, despite the provision of free ICTs at HNTC. Poor adherence and older age of patients may explain the unfavorable outcomes of DFO and (DFO+DFP) regimens, whereas younger age and higher socioeconomic status may have contributed to the lowest SF and superior outcomes in patients on DFX. This study also demonstrates the crucial role of the National Thalassemia Centers, namely HNTC, in providing health services to BTM patients in times of peace and conflict.
Topics: Humans; Animals; Cricetinae; beta-Thalassemia; Prevalence; Syria; Analysis of Variance; Iron Overload; Mesocricetus
PubMed: 37743972
DOI: 10.1155/2023/8911518