Search Results (936)

The objective of this work was to analyze the effect of reducing Fe chelate fertilization (50% and 25% reduction) on soil nutrient content and on different physiological and biochemical parameters in mandarin leaves. The reduction in Fe fertilization efficiently decreased soil Fe content, even in the short-term, without affecting leaf Fe or chlorophyll contents. Reduced iron fertilization increased the accumulation of certain heavy metals in mandarin roots, indicating potential implications for phytoremediation. It is well-established that disturbances of foliar Fe homeostasis can impair the photosynthetic process. Nevertheless, reduction in Fe supply did not negatively affect photosynthetic performance (based on chlorophyll fluorescence parameters), nor did it influence the stress levels of the trees, as indicated by lipid peroxidation. In addition, reduced iron fertilization did not alter peroxidase activity, which is considered a biochemical marker of Fe nutrition in plants. Finally, mandarin production was evaluated over two consecutive years, with no significant variations among the different iron treatments, whereas only minor differences were observed in fruit quality. Overall, these results indicate that reducing Fe fertilization is a feasible strategy, as it does not adversely affect the physiological processes or yield of mandarin trees. Furthermore, this agricultural practice can enhance nutrient use efficiency, thereby contributing to the reduction in soil and aquifer contamination while providing economic benefits to farmers. Full article

Transmetalation, the exchange of metal ions between coordination complexes and biomolecules, has emerged as a powerful design lever in cancer metallopharmacology. Using thiosemicarbazones (TSCs) as a unifying case study, we show how redox-inert carrier states such as zinc(II) or gallium(III) can convert in situ into redox-active copper(II) or iron(III/II) complexes within acidic, metal-rich lysosomes. This conditional activation localizes reactive oxygen species (ROS) generation and iron deprivation to tumor cells. We critically compare redox-active and redox-inert states, delineating how steric and electronic tuning, backbone rigidity, and sulfur-to-selenium substitution govern exchange hierarchies and kinetics. We further map downstream consequences for metal trafficking, lysosomal membrane permeabilization, apoptosis, and ferroptosis. Beyond TSCs, iron(III)-targeted transmetalation from titanium(IV)-chelator “chemical transferrin mimetics” illustrates a generalizable Trojan horse paradigm. We conclude with translational lessons, including mitigation of hemoprotein oxidation via steric shielding, stealth zinc(II) prodrugs, and dual-chelator architectures and outline biomarker, formulation, and imaging strategies that de-risk clinical development. Collectively, these insights establish transmetalation as a central therapeutic principle. We also highlight open challenges such as quantifying in-cell exchange kinetics, predicting speciation under non-equilibrium conditions, and rationally combining these agents with existing therapies. Full article

Iron metabolism has emerged as a critical regulator of cancer biology, with mounting evidence linking iron dysregulation to tumor initiation, progression, and resistance mechanisms. Osteosarcoma (OS) is the most common primary bone malignancy and a leading cause of cancer-related death in children and young adults; recent studies have identified profound alterations in iron homeostasis at both cellular and microenvironmental levels in OS. These include increased iron uptake, disrupted storage and export, and a reliance on iron-dependent metabolic pathways that promote proliferation, metastasis, and immune evasion. Despite advances in surgical and chemotherapeutic approaches, survival outcomes in OS have stagnated, underscoring the need for novel therapeutic strategies. Targeting iron metabolism represents a promising avenue, with strategies such as iron chelation, transferring receptor inhibition, ferroptosis induction, and modulation of ferritinophagy, showing preclinical efficacy. In this review, we provide an updated and integrated overview of the multifaceted role of iron in OS pathogenesis, dissect emerging therapeutic approaches aimed at disrupting iron regulatory networks, and highlight innovative delivery platforms including nanomedicine. By integrating current insights on iron metabolism with the molecular complexity of OS, we present a comprehensive perspective, while acknowledging that the limited clinical translatability of current findings still hinders progress toward clinical application. A deeper understanding of iron-driven mechanisms may guide future studies toward the development of safe and effective iron-targeted therapies for OS. Full article

Stress is a non-specific systemic response to internal or external challenges. Recent studies show that stress can disrupt iron metabolism and that iron dyshomeostasis is implicated in many diseases-particularly within the nervous system, where iron distribution and regulation intersect tightly with oxidative stress and inflammation. Activation of the hypothalamic–pituitary–adrenal (HPA) axis by stress can upregulate hepatic hepcidin and reprogram systemic iron fluxes, leading to functional iron deficiency and, in the brain, reduced iron availability, which affects myelination and neurotransmitter metabolism. Conversely, iron dyshomeostasis also contributes to neurodegenerative pathology. In this review, we synthesize recent evidence of how stress reprograms brain iron distribution and regulation, and we outline the mechanistic links between stress-induced iron dysregulation and neurological pathology. We also discuss the therapeutic implications (such as iron-chelation strategies) and highlight the three-way interplay among stress, iron metabolism, and neurodegeneration. These insights suggest that managing iron homeostasis may offer new therapeutic avenues for stress-related neural disorders. Full article

This study investigates the physicochemical processes in aqueous solutions treated with a high-current (up to 300 A) pulsed multispark discharge. Pulse length was 2 μs at a 50 Hz repetition rate. The discharge occurred within bubbles of argon injected between the stainless-steel electrodes at the constant flow rate. The erosion of electrode material during the discharge led to iron and other alloy components entering the liquid. Optical emission spectra confirmed the erosion of electrode material (Fe, Cr, Ni atoms and ions). EDTA and its disodium salt were used in order to study their effect on the metal particle formation process. Treatment with deionized water led to an increase in conductivity and the generation of hydrogen peroxide (up to 1200 µM). In contrast, the presence of EDTA and its disodium salt drastically altered the reaction pathways: the H₂O₂ yield decreased, and the solution conductivity dropped substantially for the acidic form of EDTA, while the decrease was minor for EDTA-Na₂. This effect is attributed to the buffered chelation of eroded metal ions, forming stable Fe-EDTA complexes, as confirmed by a characteristic absorption band at 260 nm. The results demonstrate the critical role of complex-forming agents in modulating plasma–liquid interactions, shifting the process from direct erosion products to the formation of stable coordination compounds. Full article

Ferroptosis, an iron-dependent form of regulated cell death, plays a pivotal role in the pathogenesis of cardiometabolic diseases (CMDs), particularly diabetic cardiomyopathy (DCM) and atherosclerosis (AS). This review comprehensively explores the metabolic pathways underlying ferroptosis, including dysregulation of iron, lipid, amino acid, and glucose metabolism, as well as involvement of the mevalonate pathway and key regulators such as NRF2 and p53. We analyze the cell type-specific mechanisms through which ferroptosis contributes to DCM and AS, driving myocardial dysfunction, plaque instability, and inflammatory amplification. Furthermore, we discuss emerging therapeutic strategies targeting ferroptosis, such as iron chelators, antioxidants, lipoxygenase inhibitors, ACSL4 inhibitors, nitroxides, and selenium supplements, which demonstrate potential in mitigating oxidative stress, restoring iron homeostasis, and suppressing inflammation. This review underscores the clinical relevance of targeting ferroptosis and highlights its promise as a novel therapeutic avenue for treating cardiometabolic diseases. Full article

Introduction: Acute iron poisoning is a potentially life-threatening condition that primarily affects the gastrointestinal, hepatic and cardiovascular systems. While it most often occurs accidentally in children, intentional overdoses in adolescents and adults remain an important clinical concern. Case description: We report the case of a 14-year-old male patient with a history of depression who intentionally ingested 100 ferrous sulfate tablets (equivalent to 118 mg/kg of elemental iron). The patient was admitted to the emergency department three hours after ingestion. He presented with vomiting tablet remnants, headache, and mild abdominal pain. Supportive measures included intestinal irrigation with polyethylene glycol (PEG), gastric protection, and N-acetylcysteine intravenous administration. The iron chelator therapy with deferoxamine was not possible because the medication was unavailable, so treatment with the oral iron chelator (deferasirox) was initiated. The iron levels gradually decreased, with no evidence of liver or cardiovascular involvement. The patient was discharged on day 20 post-ingestion with outpatient psychiatric follow-up. Discussion: This case highlights the importance of early initiation of gastrointestinal decontamination with PEG to limit systemic iron absorption. The use of deferasirox as an alternative chelating agent in the absence of deferoxamine has been associated with a favorable response. Conclusions: The rational use of oral chelators, gastrointestinal decontamination, and hepatoprotective therapies in acute iron poisoning might prevent major complications and improve prognosis. Alternative therapies can be valuable when an antidote is not immediately available; however, further clinical research is required before making a recommendation. Full article

Background: Lactiplantibacillus plantarum synthesizes in vitro hydroxyphenyllactic acid (HPLA)—an iron-reducing agent supposed to facilitate duodenal Fe absorption. So far, no such in vivo HPLA production has been established. This study aimed to investigate the ability of Lactiplantibacillus plantarum to produce HPLA in the duodenum in rats on a high-fat iron-deficient diet. Methods: Rats were fed a high fat (HF) diet; HF, Fe-deficient diet (HFDEF); or control (C) diet for 8 weeks. Over the next 8 weeks, animals in the C and HF groups continued on their respective diets, while animals in the HFDEF group were divided into six subgroups and received combinations of an HF, Fe-deficient diet with Lactiplantibacillus plantarum (Lp), Latilactobacillus curvatus (Lc), and Fe supplementation (HFDEF, HFDEFFe, HFDEFLp, HFDEFLc, HFDEFFeLp, and HFDEFFeLc). Duodenal and faecal samples were collected. Results: No significant differences were observed in HPLA content in the duodenum and faeces, nor in Fe chelating abilities in faeces, between study groups at the completion of the study. Fe content in faeces was higher in the HFDEFFe group than in the C, HF, HFDEF, HFDEFLp, and HFDEFLc groups. Fe content in faeces was higher in the HFDEFFeLp and HFDEFFeLc groups than in the HFDEF and HFDEFLc groups. Conclusions: Lactiplantibacillus plantarum, whether alone or with oral Fe, does not influence duodenal and faecal HPLA content, nor does it affect faecal Fe chelating abilities in rats on the HF, Fe-deficient diet. Full article

While the molecular mechanisms of cadmium (Cd) uptake are well-studied in rice and tobacco, hexaploid wheat remains less explored. Elucidating the roles of transporter genes in Cd uptake and translocation in wheat is critical for minimizing Cd accumulation in grains. This study compared the differences in the expression levels of Cd transporter families (including the natural resistance-associated macrophage protein (NRAMP), heavy metal ATPase (HMA), zinc-regulated transporter/iron-regulated transporter (ZIP), and yellow stripe-like (YSL) families) between two high Cd-accumulating wheat varieties and two low Cd-accumulating wheat varieties using qPCR. We found that low Cd-accumulating wheat varieties had higher expression levels of TaNRAMP5 and TaHMA2 in roots and TaHMA3 in aboveground tissues, and lower expression levels of TaNRAMP6, TaZIP5, and TaYSL6 in both roots and aboveground tissues compared to the high Cd-accumulating wheat varieties. Mantel test analysis revealed that the root expression levels of TaNRAMP5 and TaNRAMP6 and aboveground expression levels of TaZIP6 and TaHMA2 were significantly correlated with the Cd content of wheat tissues. Furthermore, the expression levels of TaZIP5 in roots and TaZIP5 and TaHMA3 in aboveground tissues were significantly correlated with the Cd translocation factor from roots to aboveground tissues, suggesting that TaNRAMP5, TaNRAMP6, TaZIP6, and TaHMA2 played key roles in Cd uptake and accumulation in wheat, and TaZIP5 and TaHMA3 were closely associated with Cd translocation from roots to aboveground tissues. Compared to low Cd-accumulating varieties, high Cd-accumulating wheat varieties exhibit significantly elevated levels of thiol-containing compounds for Cd chelation, including glutathione (7.65%~75.5% higher), phytochelatins (2.35%~47.2% higher), and non-protein thiols (13.2%~37.1% higher). These findings deepen insights into wheat Cd absorption processes. The identified transporter genes could serve as foundational resources for future breeding strategies aimed at reducing Cd accumulation in wheat, pending further functional validation. Full article

Background: Recent research has focused on diet as a potential source of antioxidants in the context of both human health and disease prevention. Among the many plant-derived antioxidants, sulforaphane (SFN) has emerged as a potent phytochemical in the recent literature for sustaining health and combating cancerous, inflammatory, and neurodegenerative diseases. Thus, the market for supplements and functional foods has been quick to adapt to this new market niche. We aimed to investigate the phytochemical profile of broccoli sprouts and evaluate their antioxidant capacity through biochemical assays. Methods: UHPLC and MS/MS were used to analyse the phytochemical characteristics of broccoli sprout extracts. Antioxidant tests, including the DPPH test, ferrous iron chelation, hydroxyl radical neutralisation, and lipoxygenase inhibition, were used to evaluate their antioxidant potential. Results: The broccoli sprout extracts emerged as an adequate source of SFN, as well as other biologically active compounds such as xanthorhamnin. Moreover, biochemical assays showcased their antioxidant capacity. Conclusions: Broccoli sprouts could constitute an important source of dietary antioxidants with high bioavailability and high accessibility, helping sustain health and even combat various diseases. Full article

Ferroptosis, an iron-dependent form of regulated cell death, is emerging as a critical pathogenic mechanism and a highly promising therapeutic target in sensorineural hearing loss (SNHL). The irreversible loss of auditory hair cells, the hallmark of SNHL, creates an urgent need for novel therapeutic strategies. This review provides a translational perspective on ferroptosis, connecting its core molecular machinery to tangible opportunities for otoprotection. We systematically analyze three key targetable nodes: the iron metabolic pathways that fuel the process; the lipid peroxidation machinery that executes membrane damage; and the collapse of the System Xc⁻–GSH–GPX4 antioxidant axis. By framing the disease mechanism through these actionable targets, we highlight a clear rationale for developing new hearing preservation therapies. We conclude by surveying the most promising pharmacological approaches, including iron chelators, radical-trapping antioxidants, and bioactive natural products, offering a strategic roadmap for future drug discovery in audiology. Full article

Coplanar tridentate nitrogen-donor ligands have been extensively employed to stabilize transition metal complexes by chelation. Some complexes exhibit interesting structures and photoluminescent properties. In this work, 2,6-bis(5-isopropyl-1H-pyrazole-3-yl)pyridine (denoted as L), its iron(II) and manganese(II) dichlorido complexes, and its bis-chelate iron(II) complexes, viz. [FeCl₂(L)]·2(MeOH) and [MnCl₂(L)]·2(MeOH), and [Fe(L)₂](PF₆) ·5(thf), respectively, were synthesized and characterized by single-crystal X-ray structural analysis. These solid-state structures contained N–H donors that formed hydrogen bonds with the coordinated halogenide ions and lattice solvent molecules, methanol or tetrahydrofuran. The iron(II) and manganese(II) dichlorido complexes [FeCl₂(L)]·2(MeOH) and [MnCl₂(L)]·2(MeOH) displayed distorted trigonal pyramidal structures in the solid state. However, [FeCl₂(L)]·2(MeOH) was not stable in methanol and formed the bis-chelate iron(II) complex [Fe(L)₂](FeCl₄). Therefore, the bis-chelate iron(II) complex [Fe(L)₂](PF₆)·5(thf) was also synthesized and structurally and spectroscopically authenticated. Full article

Antioxidant activity is a normal physiological function that is essential for healthy living, and it is maintained by antioxidant dietary nutrients. However, increases in free radical production and oxidative toxicity in many clinical conditions can cause serious and sometimes irreversible damage. Despite many investigations, including hundreds of clinical trials suggesting that there are health benefits obtained from the use of natural antioxidants, no antioxidant drugs have yet been developed for the treatment of any disease associated with free radical pathology. Millions of people choose to use nutraceutical and natural product antioxidants as therapeutics and also for chemoprevention against cancer and other diseases. New academic efforts and strategies are required for the development of antioxidant drugs in clinical practice in the absence of interest by the pharmaceutical and nutraceutical industries. One of the most effective antioxidant therapeutic strategies is inhibition by chelators of iron involved in the catalytic formation of free radical reactions and their associated damage. Hundreds of phytochelators have been shown to inhibit oxidative damage, similar to the iron-chelating drugs deferiprone and deferoxamine. In particular, several nutraceuticals and natural products such as ascorbic acid, quercetin, curcumin, fisetin, lipoic acid, and maltol have been shown to have high antioxidant activity and iron-binding capacity, as well as other effects on iron metabolism, in pre-clinical studies and clinical trials involving different categories of patients. For example, ascorbic acid and maltol–iron complexes are sold as pharmaceutical products for the treatment of iron deficiency. The development of nutraceuticals as antioxidant drugs may involve one or more applications, such as short- or long-term treatments, single-drug or combination therapies, and also different targets, such as the prevention, treatment, or post-treatment of diseases associated with free radical pathology as well as ferroptosis. The academic efforts surrounding the developments of iron-chelating nutraceuticals or natural products into antioxidant pharmaceuticals should fulfill all of the regulatory requirements and include clinical tests of antioxidants in rare or untreatable diseases, as well as the involvement of government translational research institutions and expert groups that specialize in regulatory drug affairs, among others. Full article

Black rhinoceros (Diceros bicornis) face threats to survival due to poaching in the wild and an incomplete understanding of preventive health monitoring under human care. Black rhinos under human care develop iron overload disorder (IOD) which is associated with predisposition to other disease, compromised immune function, hemolytic crisis, and death. Management of IOD is challenging but has been mitigated in some cases with dietary intervention and phlebotomy and documented through serum biomarker evaluation. Chelation therapy to reduce iron is rare in rhinos partially because of limited product availability and route of administration. An iron-specific chelator HBED (N,N’-Di(2-hydroxybenzyl)ethylenediamine-N,N’-diacetic acid) was investigated for oral use in southern black rhinos (n = 3) after successful testing was performed with equids as a model. Using a cross-over design, we tested the efficacy of short-term HBED administration. HBED was dosed at 40 mg/kg body weight for 10 days and resulted in increased urinary excretion of iron but unaltered fecal iron excretion in rhinos compared to control trials. Two rhinos maintained blood chemistry and cell distribution considered normal for the species. The third rhino experienced a hemolytic event after stopping HBED administration in the same time frame and at the same dose as the two conspecifics but fully recovered. Careful monitoring and tapering the drug at the completion of treatment is warranted, especially if the rhino’s iron load is considered high. HBED’s potential to induce iron excretion safely, as well as prevent excessive dietary iron uptake, may significantly benefit the black rhino population under human care. Full article

Ethnographic collections often incorporate composite objects consisting of various materials, including wood, textiles and metals. These objects are vulnerable to deterioration when iron fastenings corrode under humid environments, and their removal is therefore essential for the long-term preservation of artifacts. This study investigates the efficacy of the chelating agents Desferrioxamine B (DFO-B) and ethylenediaminetetraacetic acid (EDTA), applied in different gel formulations, in cleaning wooden and textile mock-ups stained with iron corrosion products. Three gel types were explored: xanthan gum, agarose and Nanorestore extra-dry gel with medium water retention (nano-MWR). The results indicated that xanthan gum exhibited the highest cleaning effectiveness but posed risks of residue deposition and surface damage due to the required clearance process. Agarose and nano-MWR gels proved to be less effective but showed potential for achieving high chelator efficacy with repeated applications. Agarose enhanced the chelators’ efficacy on textiles, while nano-MWR gel performed better on even wooden surfaces. No chemical damage was detected for either substrate across gel applications. The study concludes that a single gel formulation does not achieve equivalent cleaning efficacy on the two substrates of composite objects with a defined number of applications. Agarose in a semi-rigid state enhances the efficacy of textile treatment and may achieve comparable results on wood after repeated applications. Alternatively, a combined approach using agarose for textiles and nano-MWR gel for wood may optimize chelator performance on composite artifacts. Full article