Advances in understanding the neurotoxicity of lead, cadmium, arsenic, and therapeutic strategies.

Exploring copper metabolism and cuproptosis, and their implications in ocular diseases.

Poisoning from mercury has the potential to affect multiple organ systems and can be fatal in some circumstances. We present a case of a patient who had both ingested and inhaled elemental mercury resulting in deposits in his pulmonary and gastrointestinal systems. The patient was admitted to the intensive care unit (ICU) as a precautionary measure but did not require any organ support. The patient was treated with chelation therapy guided by the UK National Poisons Information Service (NPIS) and was discharged from ICU after having a prophylactic appendicectomy due to mercury deposition. This case presented several challenges logistically as there was a need to follow expert guidance with regards to personal protective equipment (PPE) and waste disposal, alongside the clinical requirements.

Background: Worldwide, thalassemia is the most prevalent gene defect. The main treatment of thalassemia is the blood transfusion along with chelation therapy. Repeated blood transfusions leads to iron overload along with chelation therapy detoriates liver function. This study aims to see the correlation between liver enzymes with serum ferritin in children with b-thalassemia major. Materials and methods: From Chattogram Medical College Hospital 79 children suffering from thalassemia major in the age group of 5-12 years who received regular blood transfusions and iron chelators were included in this cross sectional study. Serum ferritin and liver enzymes [Alanine Transaminase (ALT) Aspartate Transaminases (AST) Alkaline Phosphatase (ALP) and Gamma Glutamyltransfarase (GGT)] were tested and their correlation was assessed. Pearson sbivariate correlation coefficient was used to determine the correlation. Results: The mean age was 8.5±2.4 years and 57% were male. The mean age at diagnosis of thalassemia was 10.7±4.2 months and mean number of transfusion was90±29 and ranged between 40-140 transfusions. All of the children were on oral ironchelation therapy and the average age of initiation chelation therapy was 5.7±1.1years. Sixty-four (81%) children had growth retardation. Mean serum ferritin level was 3740.7±2184.8ng/ml and only 3.8% of the patients had serum ferritin level <1000 ng/ml. The mean level of serum ALT, AST, ALP, and GGT was 121.9±73.9, 89.9±49.1, 256.0±114.9 and 52.8±35.8IU/L, respectively. Respectively, 57(72.2%, 65(82.3%), 19(24.1%) and 23(29.1%) patientshad elevated ALT, AST, ALP and GGT levels. Serum ferritin had a positive correlation with ALT (r=0.639, p<0.001), AST (r=0.659, p<0.001), ALP (r=0.535, p<0.001), GGT (r=0.535, p<0.001) total number of transfusion received (r=0.539, p<0.001). Age of starting iron chelation therapy was positively correlated between and serum ferritin and liver enzyme levels (p<0.05). Conclusions: In thalassemia major patients liver enzymes are raised and positively correlated serum ferritin. Regular monitoring of liver functions is necessary to see early onset of hepatic dysfunction. JCMCTA 2025 ; 36 (1) : 129-133

Evaluation of iron chelation therapy in adults with Beta-Thalassemia major in Hilla city

ABSTRACT Background: The risk of diabetes mellitus (DM) development is a significant concern for patients with β-thalassemia major (β-TM), primarily because of iron overload from frequent blood transfusions and chelation therapy. Research indicates that DM prevalence among β-TM patients is higher than in the general population and is estimated to be 10.5% in the United Arab Emirates. This study aimed to update the data on DM prevalence and clinical correlations in this population. In addition, it evaluates the effectiveness of fructosamine as a predictive marker for DM in patients with β-TM. Methods: A total of 252 patients with β-TM were recruited in a cross-sectional study. All clinical and laboratory variables of the patients were extracted. Statistical analyses were performed using the SPSS software package. Results: Based on the medical records, 38 patients (15.1%) were found to have DM; most were over the age of 25 years. Patients with DM showed elevated random glucose and fructosamine levels compared to non-DM patients. The serum ferritin levels remained consistent. Fructosamine positively correlated with random point-of-care testing (POCT) glucose levels. Similarly, ferritin was correlated with random glucose and POCT glucose but inversely correlated with Vitamin D. Magnetic resonance imaging T2 imaging revealed moderate-to-severe pancreatic iron overload in 20 patients. Fructosamine emerged as a significant predictor of diabetes in patients with β-TM, exhibiting high accuracy. Conclusion: This study reveals a significant increase in the prevalence of DM among patients with β-TM in the United Arab Emirates, surpassing previous estimates. These findings emphasize the critical need for regular screening and proactive healthcare interventions to improve patient outcomes and enhance overall quality of life.

Background:β-Thalassemia major patients are frequently vulnerable to endocrine dysfunction due to iron overload from chronic transfusions. This impairs growth, thyroid function, glucose metabolism, and bone health, ultimately compromising quality of life and long-term outcomes.Objectives:This study investigates the prevalence and pattern of endocrine dysfunction in β-thalassemia major patients receiving iron-chelation therapy and explores associations with iron overload markers.Methods:This case-control study involved 60 β-thalassemia major patients and 20 age- and sex-matched controls. Hormonal and biochemical parameters were measured and linked to iron status.Results:Among β-thalassemia major patients (7–35 years), 73.3% (n = 44/60) were splenectomized; 36 received deferiprone, 19 deferasirox, and 5 deferoxamine. Concerning iron status, both splenectomized and non-splenectomized patients had significantly higher iron and ferritin and lower haptoglobin levels compared to controls. No significant differences were found in hepcidin or hemopexin levels. Regarding thyroid function, about 15% (n = 9/60) of β-thalassemia major patients had subclinical primary hypothyroidism. Ferritin negatively correlated with free thyroxine (r = −0.330, p = 0.010). As for glycemic status, 51.7% (n = 31/60) of β-thalassemia patients had glycated hemoglobin (HbA1c) ⩾6.5% and 38.3% (n = 23/60) showed impaired fasting blood sugar. With respect to metabolic markers, splenectomized patients had higher fibroblast growth factor 21 (FGF21) than the control (p = 0.042), while no significant group differences were found in galectin-1 or sortilin. Ferritin correlated significantly and positively with FGF21 levels (r = 0.353, p = 0.006). With respect to calcium–parathyroid–vitamin D axis, hypoparathyroidism and hyperparathyroidism were each found in 11.7% (n = 7/60) of β-thalassemia patients. Vitamin D levels were significantly lower in the β-thalassemia groups compared to controls (p = 0.0001) with 71.7% (n = 43/60) deficient despite 43.3% (n = 26/60) receiving supplements. Non-splenectomized patients had higher Procollagen Type I C-Peptide, a bone formation marker, compared to controls.Conclusion:Endocrine disturbances are common in β-thalassemia major despite chelation therapy. Incorporating endocrine assessment into routine practice is essential for early detection and management.

Thalassemia is a genetic hemoglobin disorder commonly associated with iron overload and cardiac complications from repeated transfusions. Deferiprone (DFP), an oral iron chelator, has shown potential in reducing body iron and improving cardiac function. This systematic review and meta-analysis evaluates the efficacy and safety of DFP in thalassemia patients. A systematic search of PubMed, MEDLINE, and Scopus was conducted from inception to June 8, 2025. Eligible randomized controlled trials (RCTs) enrolled thalassemia patients receiving iron chelation therapy and compared DFP (alone or in combination) with deferoxamine, deferasirox, placebo, or no chelation. Non-randomized studies, those without comparators, or lacking sufficient data were excluded. Risk of bias was assessed using the Cochrane RoB 2 tool, and certainty of evidence by GRADE. Pooled standardized mean differences (SMDs) the inclusion criteria; 18 were included in the meta-analysis. DFP significantly improved left ventricular ejection -effects model. Twenty-three RCTs (n = 1,005) met the inclusion criteria; 18 were included in the meta-analysis. DFP significantly improved left ventricular ejection fraction (SMD: 0.55) and shortening fraction (SMD: 0.37). Non-significant improvements were observed in urinary iron excretion and right ventricular ejection fraction. No significant effects were found for serum ferritin, liver iron concentration, or cardiac T2* MRI. DFP increased the risk of adverse events (RR: 1.37), but not mortality (RR: 0.30). Evidence certainty was moderate for cardiac function and adverse events, and low for other outcomes. DFP improves cardiac function and iron excretion with an acceptable safety profile in thalassemia. Further high-quality RCTs are warranted to confirm its role and optimize regimens. PROSPERO CRD420251028324.

A retrospective, unicenter case series describes five cats with primary portal vein hypoplasia (PVH). This case series outlines clinical signs, diagnostics, treatments, and prognosis in cats diagnosed with primary PVH based on histopathology. Pathology records from cats that underwent liver biopsies were retrospectively searched to identify cats with histologic features of portal vein hypoperfusion. Patients with concurrent hepatic conditions such as portosystemic shunts (PSS), portal vein obstruction, arteriovenous fistulas, and other hepatic conditions which complicate vasculature were excluded, leaving five cases for inclusion. In this case series, three of five cats were asymptomatic, with abnormalities detected on biochemistry or abdominal ultrasound, one cat presented with lethargy, and one cat presented with gastrointestinal signs associated with a foreign body. Four out of five cats in this series underwent treatment with follow-up biochemistry profiles. One cat in this study was a well-controlled diabetic and hyperthyroid while one cat was newly diagnosed with hyperthyroidism following biopsies which complicated liver enzyme interpretation. Treatment protocols were variable and encompassed management of concurrent metabolic disorders, use of hepatoprotective medications, hepatic encephalopathy therapy, antimicrobial treatment, copper chelation, and immunosuppressive therapy. A larger case series or a prospective study is necessary to establish the optimal treatment plan, as there were no established standards for managing this condition for this cohort. Four cats with confirmed follow-up had an average survival time of 878.5 days after diagnosis, indicating a favorable prognosis.

BackgroundThis study aimed to evaluate alterations in macular microstructure and blood flow density in patients with transfusion-dependent β-thalassemia (TDT) using optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA), and to explore their associations with markers of iron metabolism.MethodsA cross-sectional study was conducted involving 31 TDT patients (61 eyes) and 31 age- and sex-matched healthy controls (61 eyes) at the Affiliated Hospital of Guangdong Medical University from October 2022 to December 2023. Data collected included basic information, medical history, best-corrected visual acuity, ocular biometry, fundus photography, and OCT/OCTA imaging. Parameters assessed comprised the thickness and blood flow density of individual macular layers, as well as choroidal stromal area, choroidal luminal area, and choroidal vascular index (CVI). Pearson correlation analysis was employed to examine relationships among macular parameters, serum ferritin (SF) levels, duration of iron chelation therapy (ICT), and other variables.ResultsCompared to healthy controls, TDT patients exhibited significant thinning of the central macular area ganglion cell layer, retinal nerve fiber layer, and ganglion cell complex (mGCC), accompanied by increased blood flow density in the deep vascular complex, nerve fiber layer vascular plexus, and deep capillary plexus (all P < 0.05). The choroidal stromal area was reduced (P = 0.037), whereas CVI was elevated (P = 0.034). Pearson correlation analysis revealed a positive correlation between central mGCC thickness and the duration of ICT (r = 0.280, P < 0.05),and a significant positive correlation between CVI with SF levels (r = 0.426, P < 0.01). Stepwise linear regression analysis identified the duration of ICT (β = 0.306, P = 0.011) as a significant independent factor influencing central mGCC thickness. Similarly, SF levels significantly influenced CVI (β = 0.469, P < 0.001). Additionally, 62.30% of TDT patients’ eyes presented with tilted optic discs, 34.43% showed tessellated fundus, and 6.56% had pseudoxanthoma elasticum.ConclusionsTDT patients exhibit both macular neuroretinal thinning and increased microvascular blood flow density. CVI and central mGCC thickness may serve as potential biomarkers for monitoring iron-related ocular pathology and therapeutic efficacy. Future longitudinal studies are warranted to validate their predictive value and establish causality. Regular ocular screening is warranted in this population.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12886-025-04510-0.

Both tumors and intratumoral bacteria exhibit iron addiction, a shared metabolic dependency that drives their proliferation. Here, inspired by the ancient Chinese fable"The Snipe and the Clam Grapple While the Fisherman Profits", a nano-chelator,copper-deferiprone (Cu-DFP), is designed and synthesized to deplete iron ions by metal chelation therapy in the tumor microenvironment, thereby"sowing discord"between tumors and intratumoral bacteria and subsequently inducingcuproptosisin both. Specifically, capitalizing on the high iron stores in both tumor cells and intratumoral bacteria, coupled with the superior iron-chelating capability of DFP, Cu-DFP effectively hijacks iron ions from these cellular reservoirs while concurrently liberating substantial amounts of copper ions (Cu2+). Iron depletion not onlyexacerbates the antagonistic rivalrybetween tumors and bacteria but alsodisrupts their defense mechanismsagainst external stressors. Moreover, the released Cu2+ leads toexcessive intracellular copper accumulation, triggeringcuproptosisin both. The dying tumor cells and bacteria then release damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs), respectively, promoting dendritic cells (DCs) maturation and activatingantitumor immune responses. By harnessing the iron-mediated metabolic competition to potentiate cuproptosis, this therapeutic strategy presents an innovative method for addressing intratumoral microbiota in oncology.

Neurodegenerative diseases (NDs) are progressive and fatal disorders that primarily affect the elderly and remain incurable. Characterized by irreversible neuronal loss, they leave patients increasingly dependent on caregivers. Despite diverse clinical presentations, NDs share common pathological features, such as protein aggregation, metal accumulation, oxidative stress, and chronic neuroinflammation. Despite numerous efforts, most therapeutic candidates fail due to poor efficacy, toxicity concerns, or limited blood-brain barrier (BBB) permeability, thereby highlighting the need for enhanced formulations. Nanomedicine offers a promising strategy to improve the therapeutic performance of existing compounds. This study presents a nanoformulation of the metal chelator deferoxamine (DFO) based on the drug-structure-directing agent (DSDA) concept, in which a hydrophobic chain is covalently linked to the DFO molecule to impart amphiphilic properties and acts as a template for the synthesis of a mesoporous silica nanoparticle (MSN). This approach allows for the one-pot fabrication of DFO-loaded MSNs (DFO@MSNs) with controlled sizes of below 20 nm without the need for surfactant removal. Compared to MCM-41-based systems, DFO@MSNs exhibited a higher drug loading capacity (10 mg of DFO/100 mg of MSNs) and a significantly more sustained release profile, minimizing premature leakage, with less than 20% of the cargo released over 24 h. Safety of DFO@MSN was assessed using BV-2 microglial and human neuroblastoma SH-SY5Y cell lines, and in vitro assays confirmed its enhanced iron-chelating capacity and effective inhibition of aluminum-induced amyloid aggregation. Furthermore, permeability studies using a Caco-2 in vitro BBB model revealed that a smaller particle size greatly enhances transport across the barrier. These results support DFO@MSNs as a promising multifunctional nanoplatform for targeted chelation therapy and neuroprotection in ND treatment.

Thalassemia is a hereditary hematologic disorder characterized by defective hemoglobin synthesis, resulting in chronic anemia and rekated systemic complications, which are often managed through lifelong blood transfusions and iron chelation therapies. Recent advances in cell-based therapeutic strategies, particularly hematopoietic stem cell ( HCS ) gene therapy, have demonstrated substantial potential in addressing the underlying genetic defects and improving erythropoiesis. This systematic review evaluates preclinical and clinical studies, from PubMed, ScienceDirect, SCOPUS, focusing on the efficacy of HSC gene therapy and other immunomodulatory cellular approaches in thalassemia models. Studies involving thalassemic mice indicated that HCS-based gene therapy significantly enhanced ?-globin expression and restored normal red blood cell phenotypes, suggesting functional hematologic improvements. Complementary strategies involving regulatory T cells (Tregs) and engineered immune cells, including CAR-T and NK cells, offer additional promise for immune modulation, transplant tolerance, and the reduction of therapy-related complications. Despite these advances, challenges including limited cell availability, complex ex vivo culture conditions, immune rejection, and scalability remain. Innovations in genome editing, engineered TCR/CAR technology and CRISPR/Cas-edited iPSC-derived cells may further improve specificity, stability, and efficacy. Collectively, cell-based therapies offer a transformative approach for thalassemia by correcting the underlying genetic defect and modulating immune responses, with the potential to reduce dependence on conventional transfusions and enhance quality of life. Further clinical studies are required to establish long-term safety, feasibility and therapeutic efficiency in human patients

Before effective iron chelation became available, patients with transfusion-dependent thalassemia often died from iron-induced cardiomyopathy and endocrine failure in their second decade of life. This experience shaped long-standing expectations of poor outcomes and continues to fuel provider and patient anxiety in all conditions associated with iron overload. While severe iron overload and toxicity still cause considerable morbidity and mortality globally, advances in the understanding of iron metabolism, noninvasive organ-specific iron monitoring, and chelation therapy have significantly reduced their impact. Clinical insights from hemoglobinopathies have reinforced iron biology findings from animal models and highlighted shared mechanisms of iron toxicity across disorders, guiding broader management approaches that address the prevention of iron toxicity independently of the removal of organ iron burden. The resulting significant improvement in survival now presents new challenges tied to prolonged exposure to both anemia and iron overload, which must be addressed in long-term treatment planning.

BackgroundOxidative modifications of low-density lipoproteins (LDL) have been reported in patients with β-thalassaemia/haemoglobin E (HbE) and are related to cardiovascular complications. Deferiprone (L1) is an iron chelator that decreases iron overload and, consequently, reduces oxidative stress. This study assesses the protective effect of L1 on the oxidative status of LDL in patients with β-thalassaemia/HbE.MethodsTwenty-nine patients with β-thalassaemia/HbE treated with L1 were recruited. The study included a 4-week washout period followed by 4 and 12 weeks of L1 treatment. Non-transferrin-bound iron (NTBI) levels and oxidative stress markers, including thiobarbituric acid reactive substances and α-tocopherol, were monitored at each visit. The rate and content of lipid radical formation following Cu2+-induced LDL oxidation in vitro were detected by NBD-Pen, a specific fluorescence probe.ResultsL1 was shown to prevent the depletion of α-tocopherol, decrease thiobarbituric acid reactive substances and preserve the levels of lipid components in LDL. A negative correlation between serum NTBI and LDL α-tocopherol indicated that the circulating non-redox-active NTBI can lead to the depletion of α-tocopherol. LDL from the washout period showed the highest oxidative susceptibility when evaluated by NBD-Pen.ConclusionIron chelation therapy with L1 improves the oxidative status of LDL in patients with β-thalassaemia/HbE.

Heavy metal exposure (e.g., Pb, Cd, Hg, and As) remains a critical public health concern because of bioaccumulation and links to chronic diseases like hypertension, diabetes, and cancer. This systematic review (PRISMA compliant) synthesizes evidence from 32 studies (2015-2025) elucidating toxicity mechanisms via oxidative stress, inflammation, endocrine disruption, and epigenetic dysregulation. Key biomarkers-blood/urinary metal levels, oxidative stress markers (8-OHdG and MDA), and inflammatory cytokines (CRP, IL-6, and TNF-α)-enable early detection and toxicity assessment. Pro-inflammatory responses dominated across studies, with Pb and Cd consistently elevating CRP, TNF-α, and IL-6, alongside tissue-specific inflammation (liver and kidneys). ELISA emerged as the primary analytical method, although biomarker variability underscored influences of dose, duration, and individual susceptibility. Critically, anti-inflammatory IL-10 was frequently downregulated. We highlight the clinical utility of biomarkers in public health surveillance, chelation therapy, and preventive strategies. Future directions prioritize omics-based profiling, CRISPR technology, portable biosensors, and standardized protocols for real-time monitoring and personalized risk assessment. Integrating current biomarkers with these innovations will advance precision medicine to mitigate heavy metal toxicity globally.

Haemoglobinopathies are the most common inherited disorder of Red Blood Cells across the globe and one of the major public health problems in many regions of India. Variation in ethnic and regional prevalence is observed in many parts of India. The prevalence and pattern of haemoglobinopathies in Datia region has not been reported limiting the knowledge of disease profiles in this region. The present work aimed to find the broad view of various haemoglobinopathies in the local area and population at risk. To identify prevalence and patterns of three blood disorders namely sickle cell anaemia, β-thalassemia major and G-6-P-D deficiency samples were collected from the patients attending various OPDs of District Hospital, Datia, Madhya Pradesh, India. All anaemic patients referred by Government District Hospital, Datia District, M.P. were screened for various haemoglobinopathies. A total of 605 cases were received from September 2017 to March 2020 at the Model Rural Health Research Unit (MRHRU), Datia, M.P. All 605 samples were tested for different haemoglobinopathies by solubility test and G6PD deficiency, cellulose acetate electrophoresis, and suspected cases were confirmed from HPLC. A total of 605 patients were screened for haemoglobinopathies from District Hospital, Datia. It was found that 13 cases (2.14%) were of β thalassemia trait and other rare variants followed by 4 cases (0.66%) of sickle cell trait. A total of 3 cases (0.5%) of β thalassemia major were observed in a total sample of 605. No previous studies have reported the status of haemoglobinopathies in this region, since this region is known for tribes it is essential to have study of blood genetic disorders. Novelty of this study is that it is the first report from this region to the best of our knowledge. Very low prevalence rate of sickle cell anaemia and thalassemia was observed. So, large-scale screening in the region is required for identifying the true burden. Chelation therapy, gene therapies in future could be great help to the patients of this region.

Objective:This study aimed to evaluate whether EDTA-based targeted chelation therapy can act as senomorphic in chronic kidney disease (CKD)-induced vascular calcification.Introduction:Vascular calcification, a significant complication of CKD, is induced due to osteogenic trans-differentiation and senescence of vascular smooth muscle cells (VSMCs). Senescent VSMCs contribute to inflammation and calcification via the senescence-associated secretory phenotype (SASP). Recent evidence implicates the NLRP3 inflammasome as a key mediator of inflammation and senescence in vascular calcification. We previously demonstrated that EDTA chelation therapy removes calcium deposits from arteries in the CKD model. In this study, we investigated whether EDTA also exerts senomorphic effects by reducing NLRP3 expression and vascular cell senescence in calcified aortic tissue.Methods:We used an adenine diet-based rodent model of late-stage CKD and an ex vivo aortic ring culture model to evaluate the senotherapeutic potential of EDTA-loaded human serum albumin nanoparticles tagged with anti-elastin antibody—Flexibzumab (EDTA NPs). For validation, we performed a comparative proteomics analysis on the total proteins harvested from the abdominal aortas of the EDTA-treated and untreated animals.Results:Our results show that targeted chelation therapy with EDTA NPs decreases the percentage of SA-β-gal positive senescent cells in the calcified aorta and acts as senomorphic by decreasing NLRP3 inflammasome formation, which is a primary intracellular source of senescence-associated secretory phenotype (SASP).Conclusion:For the first time, the current study provides proof of concept on the senotherapeutic potential of a targeted chelation therapy and its capacity to modulate SASP from the senescent cells accumulated in calcified aorta.

Azo dye-based on-site assay paper kit for rapid and selective naked-eye and smartphone-assisted detection of deferoxamine drug.

Correlation of plasma lipidomic profiles with cardiometabolic disease in transfusion-dependent thalassemia patients with six-month N-acetylcysteine intervention: A prospective cohort study.