Iron-chelating Agent Research Articles

Existing Tubular Injury in β-Thalassemia Major Patients Receiving Iron Chelating Agents with Normal Creatinine Level in East Java, Indonesia.

Patients suffering from thalassemia are recipients of routine transfusions leading to hemosiderosis. Taking iron chelating agents is mandatory. Several studies have shown different results regarding the occurrence of kidney complications in thalassemia patients who received iron-chelating agents. In this study, we were looking for kidney complications by examining human NAG urine/serum and NGAL urine/serum in thalassemia community in East Java community. The study was conducted cross-sectionally in the thalassemia community in East Java with a total sample of 91 patients aged 13-48 years. All thalassemia patients filled in demographic data, transfusion routines, duration of taking iron chelating agents, and length of time diagnosed with thalassemia. Laboratory tests included routine blood tests for ferritin, ureum, serum creatinine, human NAG urine or serum, and human NGAL urine or serum. Comparison tests (t-test, Mann-Whitney, and ANOVA, Kruskal-Wallis) were conducted to see if there were significant differences in the levels of human NAG urine and human NGAL urine serum based on age, sex, blood group, duration of transfusion, routine of transfusion, duration of taking iron chelating agents, and types of iron chelating drugs. Multivariate analysis was conducted to see whether some of these categories were related to abnormalities in human NAG urine or serum and human NGAL urine or serum. All 91 patients had normal creatinine values, yet some had abnormal serum NAG. There is a significant difference in urine human NAG and urine human NGAL levels at ages over 23 years (p = 0.05 and p = 0.01). Significant differences in human NGAL serum were also found in working and student patients (p = 0.028). Serum NGAL also differed in those taking deferasirox (p = 0.030) and significantly different human NGAL urine was also found in iron overload status (Ferritin ≥ 1000 ng.ml) (p = 0.006). There is no difference between human NAG urine/serum and human NGAL urine/serum based on sex, body mass index, blood type, hemoglobin less than 10 g/dl, routine transfusion once a month, duration of using iron chelation for more than 10 years, or splenomegaly status (splenomegaly, splenectomy, or no splenomegaly). The multivariate logistic regression results showed that age above 23 was a factor associated with abnormal urine human NAG levels (aOR = 3.79, 95% CI = 1.08-13.28). Students (aOR = 4.89, 95% CI = 1.48-16.16) with ages above 23 years (aOR = 3.69, 95% CI = 1.09-12.43) showed higher risk for an abnormal serum human NGAL levels. Patients with beta-thalassemia major exhibit noticeable tubular damage. Further research is encouraged to determine other factors behind tubular damage in the thalassemia community, particularly in Indonesia.

Emerging insights into ferroptosis in cholangiocarcinoma (Review).

Cholangiocarcinoma (CCA) is a malignant tumor that arises within the biliary system, which exhibits a progressively increasing incidence and a poor patient prognosis. A thorough understanding of the molecular pathogenesis that drives the progression of CCA is essential for the development of effective molecular target therapeutic approaches. Ferroptosis is driven by excessive iron accumulation and catalysis, lipid peroxidation and the failure of antioxidant defense systems. Key molecular targets of iron metabolism, lipid metabolism and antioxidant defense systems involve molecules such as transferrin receptor, ACSL4 and GPX4, respectively. Inhibitors of ferroptosis include ferrostatin-1, liproxstatin-1, vitamin E and coenzyme Q10. By contrast, compounds such as erastin, RSL3 and FIN56 have been identified as inducers of ferroptosis. Ferroptosis serves a notable role in the onset and progression of CCA. CCA cells exhibit high sensitivity to ferroptosis and aberrant iron metabolism in these cells increases oxidative stress and iron accumulation. The induction of ferroptosis markedly reduces the ability of CCA cells to proliferate and migrate. Certain ferroptosis agonists, such as RSL3 and erastin, cause lipid peroxide build up and GPX4 inhibition to induce ferroptosis in CCA cells. Current serological markers, such as CA-199, have low specificity and cause difficulties in the diagnosis of CCA. However, novel techniques, such as non-invasive liquid biopsy and assays for oxidative stress markers and double-cortin-like kinase 1, could improve diagnostic accuracy. CCA is primarily treated with surgery and chemotherapy. A close association between the progression of CCA with ferroptosis mechanisms and related regulatory pathways has been demonstrated. Therefore, it could be suggested that multi-targeted therapeutic approaches, such as ferroptosis inducers, iron chelating agents and novel modulators such as YL-939, may improve treatment efficacy. Iron death-related genes, such as GPX4, that are highly expressed in CCA and are associated with a poor prognosis for patients may represent potential prognostic markers for CCA. The present review focused on molecular targets such as p53 and ACSL4, the process of targeted medications in combination with PDT in CCA and the pathways of lipid peroxidation, the Xc-system and GSH-GPX4 in ferroptosis. The present review thus offered novel perspectives to improve the current understanding of CCA.

Attenuation of TNF-α and Iron Levels in Renal Hemosiderosis by Phaleria macrocarpa (Scheff.) Boerl Extract in a Rat Iron Overload Model

Regular blood transfusions are typically used to treat the genetic anemia known as thalassemia, which can lead to an increase in the body's total iron levels. The condition of excess iron can be toxic to the body due to the formation of free radicals that are harmful and can damage cells and tissues. So the availability of free iron will form the basis of iron toxicity because it accelerates the Fenton reaction to produce an increase in the amount of ROS that cannot be suppressed so that saturation of the antioxidant system can occur. Excess iron has been known to be a risk factor for organ dysfunction and damage that results in various organ diseases such as liver, heart and kidney, diabetes mellitus, and neurodegenerative diseases. Mangiferin is an active compound has been shown to act as an iron chelating agent by forming complexes with iron. The complex formed can reduce iron accumulation in thalassemia patients who receive blood transfusions on a regular basis. Mahkota Dewa (Phaleria macrocarpa) is a well-known medicinal plant native to Papua, Indonesia, and it also includes the active ingredient mangiferin. This study aims to determine the effectiveness of the ethanolic extract of Phaleria macrocarpa fruit as an iron chelating agent observed in the kidneys in a rat model of excess iron

Disproportionality analysis of data from VigiBase and other global product safety databases on toxicity of iron chelating agents

ABSTRACT Background Iron chelators; deferasirox, deferiprone, and deferoxamine; used to treat iron toxicities due to excessive ingestions or blood transfusions, may cause serious adverse reactions. Research design and methods This study investigates pharmacovigilance data to uncover unknown safety information. Disproportionality analysis was conducted using VigiBase, the WHO global database of individual case safety reports, to known safety profile of products and the FDA Adverse Event Reporting System, reviewing over 117.000 iron chelator cases between 2010 and 2020. Results Commonly reported adverse events for iron chelators are general disorders and administration site conditions and GI-related disorders. Reporting Odds Ratio was calculated for iron chelator associations to headache (common), blurred vision (rare) and sepsis (serious). Strong association between deferoxamine and blurred vision (ROR: 2.47 in VigiBase and 3.04 in FAERS), deferiprone and sepsis (ROR; 5.95 in VigiBase and 1.24 in FAERS) were identified. However, results showed some inconsistent associations, such as headache and deferiprone, blurred vision and deferasirox association as per FAERS data; sepsis and deferasirox and deferoxamine association as per VigiBase data. Forty-five new potential signals with different associative values were suggested. Conclusion The study identified strong associations between specific iron chelators and adverse events, though some inconsistencies were observed in the data. These findings, including the 45 new potential signals, suggest areas for further review and validation with additional data.

Application of validated UV-Vis spectrophotometry-colorimetric methods for specific quantification of deferiprone in the development of iron-responsive nanoparticle loaded into dissolvingmicroneedle.

Deferiprone (DFP) is one of the iron-chelating agents used in iron overload therapy for patients with ß-thalassemia major (ß-TM). However, the use of DFP is limited as it experiences a first-pass effect and can potentially cause iron deficiency due to uncontrolled release. Therefore, iron-responsive (NP-IR) DFP nanoparticle innovation was developed to control DFP release. A dissolving microneedle system (NP-IR-DMNs) was used to maximize DFP release. However, in support of this development, validation of analytical methods using spectrophotometry and colorimetrics was carried out. UV-Vis spectrophotometry is an approach that is easy to use, practical, and more cost-effective than others. The DFP levels were determined in normal and iron-overloaded medium solutions with 1%, 2%, and 4% concentrations. In addition, DFP levels were also measured in rat plasma using the colorimetric method with the addition of FeCl3 reagent to increase sensitivity for the detection of the analyte. The procedures used as guidelines in the validation procedure are The International Council for Harmonization (ICH). As a result, all linear correlation values of medium and plasma ≥ 0.999 were obtained. The LOQ levels obtained were 0.55µg/mL, 0.44µg/mL, 0.42µg/mL, 0.52µg/mL, and 1.01µg/mL in plasma, 1% FeSO4, 2% FeSO4, 4% FeSO4, and normal media, respectively. The accuracy and precision were confirmed valid, as all values were within the requirements and did not change during dilution. Then, this approach was successfully applied to determine the levels of DFP in NP-IR integrated into DMNs.

Amphetamine-like Deferiprone and Clioquinol Derivatives as Iron Chelating Agents.

The accumulation of iron in dopaminergic neurons can cause oxidative stress and dopaminergic neuron degeneration. Iron chelation therapy may reduce dopaminergic neurodegeneration, but chelators should be targeted towards dopaminergic cells. In this work, two series of compounds based on 8-hydroxyquinoline and deferiprone, iron chelators that have amphetamine-like structures, have been designed, synthesized and characterized. Each of these compounds chelated iron ions in aqueous solution. The hydroxyquinoline-based compounds exhibited stronger iron-binding constants than those of the deferiprone derivatives. The hydroxyquinoline-based compounds also exhibited greater free radical scavenging activities compared to the deferiprone derivatives. Molecular dynamics simulations showed that the hydroxyquinoline-based compounds generally bound well within human dopamine transporter cavities. Thus, these compounds are excellent candidates for future exploration as drugs against diseases that are affected by iron-induced dopaminergic neuron damage, such as Parkinson's disease.

Prevalence of iron overload in patients with chronic kidney disease on peritoneal dialysis: A scoping review.

Chronic kidney disease (CKD) patients undergoing peritoneal dialysis (PD) are susceptible to complications, including iron overload, which can significantly impact their prognosis and overall health. This scoping review aimed to study the prevalence and implications of iron overload in CKD patients undergoing PD. A comprehensive search was conducted across five databases, leading to the selection of 18 papers for in-depth analysis. These studies collectively involved 381 PD patients, 60.3% were males. No consensus was reached regarding the exact diagnostic cutoff for iron overload. The investigations revealed four main aspects: (1) Seven papers identified various factors contributing to iron overload, emphasizing the role of different iron supplements and magnetic resonance imaging's capability to diagnose iron accumulation in organs; (2) Iron overload in young patients was found to hinder growth; (3) Six studies highlighted the adverse effects of iron overload, with cardiac issues being the most significant; (4) Three studies demonstrated the efficacy of iron-chelating agents, Deferoxamine and Deferasirox, in treating iron overload patients undergoing PD. Overall, the estimated prevalence of liver iron overload in CKD patients on PD ranges from approximately 10% to 28.6%, which is far lower than the prevalence of 75% elegantly shown in HD patients. While iron overload was a significant concern for CKD patients undergoing PD in the past, it is less common in the current era due to advancements in treatments, such as erythropoiesis-stimulating agents. Treatment with specific chelation agents has proven beneficial, but there is also a risk of adverse effects, necessitating meticulous monitoring and timely intervention.

Ferroptosis promotes valproate-induced liver steatosis in vitro and in vivo

Valproic acid (VPA), a common antiepileptic drug, can cause liver steatosis after long-term therapy. However, an impact of ferroptosis on VPA-induced liver steatosis has not been investigated. In the study, treatment with VPA promoted ferroptosis in the livers of mice by elevating ferrous iron (Fe2+) levels derived from the increased absorption by transferrin receptor 1 (TFR1) and the decreased storage by ferritin (FTH1 and FTL), disrupting the redox balance via reduced levels of solute carrier family 7 member 11 (SLC7A11), glutathione (GSH), and glutathione peroxidase 4 (GPX4), and augmenting acyl-CoA synthetase long-chain family member 4 (ACSL4) -mediated lipid peroxide generation, accompanied by enhanced liver steatosis. All the changes were significantly reversed by co-treatment with an iron-chelating agent, deferoxamine mesylate (DFO) and a ferroptosis inhibitor, ferrostatin-1 (Fer-1). Similarly, the increases in Fe2+, TFR1, and ACSL4 levels, as well as the decreases in GSH, GPX4, and ferroportin (FPN) levels, were detected in VPA-treated HepG2 cells. These changes were also attenuated after co-treatment with Fer-1. It demonstrates that ferroptosis promotes VPA-induced liver steatosis through iron overload, inhibition of the GSH-GPX4 axis, and upregulation of ACSL4. It offers a potential therapy targeting ferroptosis for patients with liver steatosis following VPA treatment.

Tandem mass tag-based quantitative proteomic analysis of metformin's inhibitory effects on ovarian cancer cells.

Metformin (MET), a type 2 diabetes treatment, has attracted increased attention for its potential antitumor properties; however, the precise mechanism underlying this activity remains unclear. Our previous in vivo and in vitro studies revealed MET's inhibitory effect on ovarian cancer, with the synergistic effects of MET and the MDM2 inhibitor RG7388 contributing to ovarian cancer treatment. This study further explores the mechanism underlying MET's inhibition of ovarian cancer. Following MET treatment, we analyzed the differentially expressed proteins in ovarian cancer cells using a tandem mass tag (TMT)-based proteomic approach coupled with bioinformatics. Using A2780 and SKOV3 ovarian cancer cells, we identified six upregulated and two downregulated proteins after MET treatment. Bioinformatics analysis revealed that these proteins predominately affect ovarian cancer cells by regulating iron ion transport, iron ion homeostasis, and mitochondrial and ribosomal functions. Validation via western blot confirmed MET-induced elevation of hydroxybutyrate dehydrogenase type 2 (BDH2) protein expression levels in A2780 and SKOV3 cells. Overall, our findings suggest that combining MET with other metabolic drugs, such as iron-chelating agents and mitochondrial inhibitors, may result in synergistic antitumor effects, thereby offering novel avenues for ovarian cancer treatment development.

Awareness and practical evaluation of correct use of iron chelators; a study to track the ambiguities of thalassemia patients on their medications in Iran

PurposeThis study aimed to evaluate the knowledge, attitude, and practice toward iron chelating agents (ICAs) in Iranian thalassemia major patients.MethodsA total of 101 patients with thalassemia major were involved in this cross-sectional survey. A deep medication review was done, and participants’ knowledge, attitude, and practice were evaluated by a validated instrument based on a 20-scoring system.ResultsStatistical analyses showed 52 patients (51.5%) had a poor knowledge level (scores < 10) about their medications, 37 (36.6%) had a moderate level (scores 10–15), and 12 (11.9%) had a satisfactory level (scores > 15). Seventy-seven (76.2%) patients have positive beliefs regarding the dependence of their current health status on taking iron chelators, and 63 (62.4%) believed that they would become very ill without taking medication. The results also showed that the mean practice score in patients who received deferoxamine was 5.81 ± 3.50; in the patients who received deferiprone and those who received deferasirox, the mean scores were 7.36 ± 5.15 and 14.94 ± 4.14. Also, the knowledge and practice level had a direct linear correlation based on the regression analyses (P < 0.001).ConclusionIn conclusion, results of the present research suggests that the patients’ knowledge about the administration, adverse events, and necessity of ICAs was not satisfactory. Improving the knowledge of thalassemia patients toward their medicines through educational interventions is highly recommended to improve their practice level.

#2308 The effect of Dapagliflozin on albuminuria and biomarkers associated with renal function in patients with β-thalassemia and/or sickle-cell disease

Abstract Background and Aims Patients with β-thalassemia present already from the 1st year of life with serious anemia thus needing regular blood transfusions in order to attain normal hemoglobin levels. Chronic anemia, iron overload and the use of iron chelating agents have been associated with renal dysfunction. In sickle-cell syndromes, which include sickle-cell anemia and sickle-cell trait, patients present with typical kidney functional and structural defects, resulting in urinary concentrating defects, distal nephron dysfunction and albuminuria. Sodium–glucose cotransporter-2 inhibitors (SGLT-2i) have shown beneficial effects on renal outcomes in large clinical trials with the added benefit of a substantial decrease in albuminuria. The aim of this prospective, non randomized open label study is to investigate the effect of Dapagliflozin at a dose of 10 mg daily on albuminuria and the overall progression of CKD in patients with β-thalassemia and/or sickle-cell disease undergoing regular blood transfusions. Method In this study we included adult patients undergoing regular blood transfusions with a baseline albuminuria of ACR&amp;gt;30 mg/gCr (assessed with a spot urine sample) who received treatment with Dapagliflozin, a second group with no albuminuria that did not receive treatment and a group of adults with no kidney disease (Controls). In all patients renal function biomarkers were measured in urine and serum with commercial ELISA kits (NGAL and uPAR in serum, MMP9 and KIM-1 in urine), while in patients that received Dapagliflozin additional measurements of ACR and eGFR (CKD-EPI formula) were performed after 3 months of treatment initiation. Results In this study we included 16 patients (7 males) with β-thalassemia and/or sickle-cell disease with ACR&amp;gt;30 mg/gCr, 35 patients (17 males) with β-thalassemia and/or sickle-cell disease without albuminuria and 20 controls (13 males). Patients that received Dapagliflozin showed a significant reduction in albuminuria three months post-initiation of treatment (ACR: 0.52 ± 1.2 vs. 0.3 ± 0.68 mg/g, p=0.006) while kidney function showed a slight non-significant reduction (eGFR: 99.3 ± 21.7 vs. 94.7 ± 28.9 ml/min/1.73m2, p=0.36). Concerning the urine and serum biomarkers of tubular dysfunction, inflammation and kidney disease progression, all were significantly increased in patients with β-thalassemia and/or sickle-cell disease in comparison to controls (Table 1). In patients that received treatment with Dapagliflozin, NGAL, MMP-9 and suPAR at 3 months post-treatment initiation did not show any significant reduction (Table 2). Conclusion Patients with β-thalassemia and/or sickle-cell disease show increased urine and serum levels of kidney damage biomarkers in comparison to healthy controls. Treatment of these patients with Dapagliflozin for 3 months has a significant effect in albuminuria reduction while it does not alter urine and serum levels of these biomarkers.

Formulation, Optimization and Evaluation of Solid Dispersion of Deferasirox Using Factorial Design

Deferasirox, an oral iron-chelating agent, is a poorly soluble drug (Biopharmaceutical Classification System class II) having insufficient solubility in physiological fluids resulting in low bioavailability of the drug. The idea behind the present study was to explore the prospects of solid dispersion as a prolific method to enhance the dissolution rate of drug using a water soluble polymer. The solid dispersion was prepared by the solvent evaporation technique using Polyvinyl pyrrolidone with different drug to carrier and solvent ratio. Formulations were characterized through attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), differential scanning calorimetry (DSC), Powder X-ray diffraction (XRD), and in vitro release studies. A 32 factorial design was implemented to obtain optimum solubility, % yield, and optimization of solid dispersion (SD) also quantitates the influence of PVP on the solubility and dissolution profile. Thedrug-to-carrier and solvent ratio was chosen as independent variable, while %yield, drug content, and saturation solubility were chosen as dependent variables. The results showed that the optimized formulation of SD-DFX was able to significantly enhance its solubility. The SD containing a dispersion of Deferasirox with PVP show an exceptional rise in the solubility. This study describes the development of solid dispersion that significantly improved the solubility and bioavailability of DFX. The FTIR studies indicate the interaction between the drug and polymer. The DSC and XRD analysis indicated that the drug was in an amorphous state when dispersed in the polymer. It is resolved that the SD method significantly improves the solubility and dissolution rate, which could also be exploit for other poorly water soluble drug candidates. Keywords: Deferasirox , Polyvinyl pyrrolidone, solid dispersion, Factorial design, Solubility

Iron chelators: as therapeutic agents in diseases.

The concentration of iron is tightly regulated, making it an essential element. Various cellular processes in the body rely on iron, such as oxygen sensing, oxygen transport, electron transfer, and DNA synthesis. Iron excess can be toxic because it participates in redox reactions that catalyze the production of reactive oxygen species and elevate oxidative stress. Iron chelators are chemically diverse; they can coordinate six ligands in an octagonal sequence. Because of the ability of chelators to trap essential metals, including iron, they may be involved in diseases caused by oxidative stress, such as infectious diseases, cardiovascular diseases, neurodegenerative diseases, and cancer. Iron-chelating agents, by tightly binding to iron, prohibit it from functioning as a catalyst in redox reactions and transfer iron and excrete it from the body. Thus, the use of iron chelators as therapeutic agents has received increasing attention. This review investigates the function of various iron chelators in treating iron overload in different clinical conditions.

Pantothenate kinase-associated neurodegeneration (PKAN) a rare neurodegenerative disease-Two case reports

Neurodegeneration with brain iron accumulation (NBIA) is a subtype of inherited metabolic disorders. It includes pantothenate kinase-associated neurodegeneration (PKAN), which is a rare autosomal recessive disorder caused by the mutation of pantothenate kinase 2-gene (PANK2). It affects the deep grey matter nuclei causing progressive extra pyramidal motor impairment. We present two cases who are presented in our department with walking difficulty, dystonia and dysarthria. MRI of brain (T2) showed- hyper intensity of the basal ganglia with the classic eye-of-the-tiger sign and one child's genetic study revealed mutation in PANK2 gene. We managed them with anti dystonic drugs along with iron chelating agent. J Bangladesh Coll Phys Surg 2024; 42: 209-213

Ferroptosis resists intracellular Vibrio splendidus AJ01 mediated by ferroportin in sea cucumber Apostichopus japonicus

Ferroptosis, a kind of programmed cell death, is characterized with iron-dependent lipid ROS buildup, which is considered as an important cellular immunity in resisting intracellular bacterial infection in mammalian macrophages. In this process, lipid ROS oxidizes the bacterial biofilm to inhibit intracellular bacteria. However, the function of ferroptosis in invertebrate remains unknown. In this study, the existence of ferroptosis in Apostichopus japonicus coelomocytes was confirmed, and its antibacterial mechanism was investigated. First, our results indicated that the expression of glutathione peroxidase (AjGPX4) was significantly inhibited by 0.21-fold (p < 0.01) after injecting A. japonicus with the ferroptosis inducer RSL3, and the contents of MDA (3.93-fold, p < 0.01), ferrous iron (1.40-fold, p < 0.01), and lipid ROS (3.10-fold, p < 0.01) were all significantly increased under this condition and simultaneously accompanied with mitochondrial contraction and disappearance of cristae, indicating the existence of ferroptosis in the coelomocytes of A. japonicus. Subsequently, the contents of ferrous iron (1.40-fold, p < 0.05), MDA (2.10-fold, p < 0.01), ROS (1.70-fold, p < 0.01), and lipid ROS (2.50-fold, p < 0.01) were all significantly increased, whereas the mitochondrial membrane potential and GSH/GSSG were markedly decreased by 0.68-fold (p < 0.05) and 0.69-fold (p < 0.01) under Vibrio splendidus (AJ01) infection. This process could be reversed by the iron-chelating agent deferoxamine mesylate, which indicated that AJ01 could induce coelomocytic ferroptosis. Moreover, the results demonstrated that the intracellular AJ01 load was clearly decreased to 0.49-fold (p < 0.05) and 0.06-fold (p < 0.01) after treating coelomocytes with RSL3 and ferrous iron, which indicated that enhanced ferroptosis could inhibit bacterial growth. Finally, subcellular localization demonstrated that ferrous iron efflux protein ferroportin (AjFPN) and intracellular AJ01 were co-localized in coelomocytes. After AjFPN interference (0.58-fold, p < 0.01), the signals of ferrous iron and lipid ROS levels in intracellular AJ01 were significantly reduced by 0.38-fold (p < 0.01) and 0.48-fold (p < 0.01), indicating that AjFPN was an important factor in the introduction of ferroptosis into intracellular bacteria. Overall, our findings indicated that ferroptosis could resist intracellular AJ01 infection via AjFPN. These findings provide a novel defense mechanism for aquatic animals against intracellular bacterial infection.

MALDI-mass spectrometry imaging as a new technique for detecting non-heme iron in peripheral tissues via caudal vein injection of deferoxamine.

As one of the most common iron-chelating agents, deferoxamine (DFO) rapidly chelates iron in the body. Moreover, it does not compete for the iron characteristic of hemoglobin in the blood cells, which is common in the clinical treatment of iron poisoning. Iron is a trace element necessary to maintain organism normal life activities. Iron deficiency can lead to anemia, whereas iron overload can cause elevated levels of cellular oxidative stress and cell damage. As a consequence, detection of the iron content in tissues and blood is of great significance. The traditional techniques for detecting the iron content include inductively coupled plasma-mass spectrometry and atomic absorption spectrometry, which cannot be used for imaging purposes. Laser ablation-ICP-MS and synchrotron radiation micro-X-ray fluorescence can map the concentration and distribution of iron in tissues. However, these methods can only be used to measure the total iron levels in blood or tissues. In recent years, due to the deepening understanding of iron metabolism, diseases related to iron overload have attracted increasing attention. Therefore, we took advantage of the properties of DFO in terms of chelating iron and investigated different sampling times following DFO injection in the tail vein of mice. We used mass spectrometry imaging (MSI) technology to detect the DFO and ferrioxamine content in the blood and different tissues to indirectly characterize the non-heme iron content.

Deferasirox Causes Leukaemia Cell Death through Nrf2-Induced Ferroptosis.

Acute lymphoblastic leukaemia (ALL) is the most prevalent cancer in children, and excessive iron buildup resulting from blood transfusions and chemotherapy potentially has a negative impact on treatment outcomes and prognosis in patients with ALL. Therefore, initiating early iron chelation therapy during ALL treatment is a logical approach. Ideally, the selected iron chelator should also possess anti-leukaemia properties. The aim of the present study was to explore the potential impact and underlying mechanism of deferasirox (DFX) in ALL therapy. This study proved that DFX, an iron chelator, is capable of inducing leukaemia cell death through ferroptosis, which is achievable by increasing the expression of acetylated nuclear factor erythroid 2-related factor 2 (NRF2). More specifically, NRF2 acetylation on Lys599 was facilitated by acetyltransferase-p300/CBP. These findings indicate that DFX could serve as a potent adjunctive medication for patients with ALL. Moreover, DFX may offer dual benefits in ALL treatment, functioning as both an iron chelator and NRF2-modulating agent. Further research and clinical trials are necessary to fully elucidate the therapeutic potential of DFX in patients with ALL and incorporate it into treatment protocols.

Pseudomonas siderophores: production, spectrophotometry detection and Botrytis suppression

Siderophores are iron-chelating agents produced by almost all microorganisms in response to iron deficiency. Due to the requirement of iron for cell growth and metabolism, siderophore-mediated acquisition of iron plays a central role in determining the ability of different microorganisms to colonize plant roots and contributes to microbial interactions in the plant rhizosphere. In this study, five new Pseudomonas (Q14B, Q13B, Q7B, Q6B, Q1B), isolated from the rhizosphere of tomato in Morocco, were examined for siderophores production capacity. The results show that all five isolates produced siderophores on both solid and liquid mediums. In liquid medium, the highest level of production is obtained by Q13B (53.8%). Concerning siderophores’ chemical types, the five strains of Pseudomonas produce two types of siderophores hydroxamate and catecholate. It was shown by the peaks of absorbance in the wavelength 495 and between 420-450 nm for catecholate and hydroxamate-type siderophores respectively. The results showed that the production of siderophores is progressively inhibited with increasing concentrations of iron in the medium. The maximum production was obtained with a concentration of 0.5 μM, while the lowest was recorded at 10.0 μM of iron. The results of this study showed that the five Pseudomonas isolates producing siderophores could be potential biological control agents.

Retracted: Iron-Chelating Agent Can Maintain Bone Homeostasis Disrupted by Iron Overload by Upregulating Wnt/Beta-Catenin Signaling.

[This retracts the article DOI: 10.1155/2020/8256261.].

Multifunctional asymmetric bi-ligand iron chelating agents towards low-cost, high performance, and stable zinc-iron redox flow battery

Zinc‑iron flow batteries hold great potential as stationary storage due to their attractive cost and abundance of materials; however, they still suffer from precipitation problems. This work demonstrates a novel asymmetric iron complex with bi-ligand from pyridine and disodium 4,5-dihydroxy-1,3-benzenedisulfonate (TIRON) to synergically reduces precipitation, improves the mass transport of the redox-active species, and lowers the electron transfer resistance. The low activation barrier of mixed complexes calculated via the Density Functional Theory (DFT) explains the ease of redox reaction, which is reflected in the low overpotential voltage in the Fe//Fe symmetrical cell. Moreover, no change in Raman and Fourier-transform infrared spectroscopy peaks after symmetrical cell cycling confirms the stability of the mixed complexes catholyte. Contrary to other works, our strategy requires a lower molar ratio of complexes per iron, while still yields a superior capacity of 6.81 Ah/L. From its outstanding capacity utilization, the overall cost of the electrolytes for the mixed complexes system is only $26.3/kWh, which is lower than the non-complex iron system at $42.9/kWh. Additionally, the mixed complexes battery can be operated stably for >200 cycles. Our perspective on eco-friendly and low-cost catholyte design accelerates development towards reliable stationary storage with high performance and stability.