Iron Toxicity Research Articles

Formation of intraneuronal iron deposits following local release from nanostructured silica injected into rat brain parenchyma

Nanostructured materials with controllable properties have been used to cage and release various types of compounds. In the present study, iron-loaded nanostructured sol-gel SiO2–Fe materials were prepared and injected into the rat brain to develop a method for gradual iron delivery into the neurons with the aims to avoid acute iron toxicity and develop an animal model of gradual, metal-induced neurodegeneration. Nanoparticles were prepared by the traditional method of hydrolysis and condensation reactions of tetraethyl orthosilicate at room temperature and subsequent heat treatment at 200 °C. FeSO4 was added in situ during the silica preparation. The resulting materials were characterized by UV-VIS and infrared spectroscopies, X-ray diffraction, and N2 adsorption-desorption. An in vitro ferrous sulfate release test was carried out in artificial cerebrospinal fluid as the release medium showing successful ferrous sulfate loading on nanostructured silica and sustained iron release during the test time of 10 h. Male Wistar rats administered with SiO2–Fe nanoparticles in the substantia nigra pars compacta (SNpc) showed significant intraneuronal increase of iron, in contrast to the animals administered with FeSO4 that showed severe neuronal loss, 72 h post-treatment. Both treatments induced lipid fluorescent product formation in the ventral midbrain, in contrast to iron-free SiO2 and PBS-only injection controls. Circling behavior was evaluated six days after the intranigral microinjection, considered as a behavioral end-point of brain damage. The apomorphine-induced ipsilateral turns in the treated animals presented significant differences in relation to the control groups, with FeSO4 administration leading to a dramatic phenotype, compared to a milder impact in SiO2–Fe administrated animals. Thus, the use of SiO2–Fe nanoparticles represents a slow iron release system useful to model the gradual iron-accumulation process observed in the SNpc of patients with idiopathic Parkinson's disease.

Iron-induced kidney cell damage: insights into molecular mechanisms and potential diagnostic significance of urinary FTL.

Background: Iron overload can lead to organ and cell injuries. Although the mechanisms of iron-induced cell damage have been extensively studied using various cells, little is known about these processes in kidney cells. Methods: In this study, we first examined the correlation between serum iron levels and kidney function. Subsequently, we investigated the molecular impact of excess iron on kidney cell lines, HEK293T and HK-2. The presence of the upregulated protein was further validated in urine. Results: The results revealed that excess iron caused significant cell death accompanied by morphological changes. Transcriptomic analysis revealed an up-regulation of the ferroptosis pathway during iron treatment. This was confirmed by up-regulation of ferroptosis markers, ferritin light chain (FTL), and prostaglandin-endoperoxide synthase 2 (PTGS2), and down-regulation of acyl-CoA synthetase long-chain family member 4 (ACSL4) and glutathione peroxidase 4 (GPX4) using real-time PCR and Western blotting. In addition, excess iron treatment enhanced protein and lipid oxidation. Supportively, an inverse correlation between urinary FTL protein level and kidney function was observed. Conclusion: These findings suggest that excess iron disrupts cellular homeostasis and affects key proteins involved in kidney cell death. Our study demonstrated that high iron levels caused kidney cell damage. Additionally, urinary FTL might be a useful biomarker to detect kidney damage caused by iron toxicity. Our study also provided insights into the molecular mechanisms of iron-induced kidney injury, discussing several potential targets for future interventions.

Implications of tolerance to iron toxicity on root system architecture changes in rice (Oryza sativa L.)

IntroductionToxicity due to excess soil iron (Fe) is a significant concern for rice cultivation in lowland areas with acidic soils. Toxic levels of Fe adversely affect plant growth by disrupting the absorption of essential macronutrients, and by causing cellular damage. To understand the responses to excess Fe, particularly on seedling root system, this study evaluated rice genotypes under varying Fe levels.MethodsSixteen diverse rice genotypes were hydroponically screened under induced Fe levels, ranging from normal to excess. Morphological and root system characteristics were observed. The onset of leaf bronzing was monitored to identify the toxic response to the excess Fe. Additionally, agronomic and root characteristics were measured to classify genotypes into tolerant and sensitive categories by computing a response stability index.ResultsOur results revealed that 460 ppm of Fe in the nutrient solution served as a critical threshold for screening genotypes during the seedling stage. Fe toxicity significantly affected root system traits, emphasizing the consequential impact on aerial biomass and nutrient deprivation. To classify genotypes into tolerant and sensitive categories, leaf bronzing score was used as a major indicator of Fe stress. However, the response stability index provided a robust basis for classification for the growth performance. Apart from the established tolerant varieties, we could identify a previously unrecognized tolerant variety, ILS 12–5 in this study. Some of the popular mega varieties, including BPT 5204 and Pusa 44, were found to be highly sensitive.DiscussionOur findings suggest that root system damage, particularly in root length, surface area, and root volume, is the key factor contributing to the sensitivity responses under Fe toxicity. Tolerant genotypes were found to retain more healthy roots than the sensitive ones. Fe exclusion, by reducing Fe2+ uptake, may be a major mechanism for tolerance among these genotypes. Further field evaluations are necessary to confirm the behavior of identified tolerant and sensitive lines under natural conditions. Insights from the study provide potential scope for enhancement of tolerance through breeding programs as well as throw light on the role root system in conferring tolerance.

Identification and validation of an immunotherapeutic signature for colon cancer based on the regulatory patterns of ferroptosis and their association with the tumor microenvironment

The integrated landscape of ferroptosis regulatory patterns and their association with colon microenvironment have been demonstrated in recent studies. However, the ferroptosis-related immunotherapeutic signature for colon cancer (CC) remains unclear. We comprehensively evaluated 1623 CC samples, identified patterns of ferroptosis modification based on ferroptosis-associated genes, and systematically correlated these patterns with tumor microenvironment (TME) cell infiltration characteristics. In addition, the ferroptosis-regulated gene score (FRG-score) was constructed to quantify the pattern of ferroptosis alterations in individual tumors. Three distinct patterns of ferroptosis modification were identified, including antioxidant defense, iron toxicity, and lipid peroxidation. The characteristics of TME cell infiltration under these three patterns were highly consistent with the three immune phenotypes of tumors, including immune-inflamed, immune-excluded and immune-desert phenotypes. We also demonstrated that evaluation of ferroptosis regulatory patterns within individual tumors can predict tumor inflammatory status, tumor subtype, TME stromal activity, genetic variation, and clinical outcome. Immunotherapy cohorts confirmed that patients with low FRG-scores showed remarkable therapeutic and clinical benefits. Furthermore, the hub gene apolipoprotein L6 (APOL6), a drug-sensitive target associated with cancer cell ferroptosis, was identified through our proposed novel key gene screening process and validated in CC cell lines and scRNA-seq.

Breaking-Down Tumoral Physical Barrier by Remotely Unwrapping Metal-Polyphenol-Packaged Hyaluronidase for Optimizing Photothermal/Photodynamic Therapy-Induced Immune Response.

The therapy of solid tumors is often hindered by the compact and rigid tumoral extracellular matrix (TECM). Precise reduction of TECM by hyaluronidase (HAase) in combination with nanotechnology is promising for solid tumor therapeutics, yet remains an enormous challenge. Inspired by the treatment of iron poisoning, here a remotely unwrapping strategy is proposed of metal-polyphenol-packaged HAase (named PPFH) by sequentially injecting PPFH and a clinically used iron-chelator deferoxamine (DFO). The in situ dynamic disassembly of PPFH can be triggered by the intravenously injected DFO, resulting in the release, reactivation, and deep penetration of encapsulated HAase inside tumors. Such a cost-effective HAase delivery strategy memorably improves the subsequent photothermal and photodynamic therapy (PTT/PDT)-induced intratumoral infiltration of cytotoxic T lymphocyte cells and the cross-talk between tumor and tumor-draining lymph nodes (TDLN), thereby decreasing the immunosuppression and optimizing tumoricidal immune response that can efficiently protect mice from tumor growth, metastasis, and recurrence in multiple mouse cancer models. Overall, this work presents a proof-of-concept of the dynamic disassembly of metal-polyphenol nanoparticles for extracellular drug delivery as well as the modulation of TECM and immunosuppressive tumor microenvironment.

Interplay of Ferroptosis and Cuproptosis in Cancer: Dissecting Metal-Driven Mechanisms for Therapeutic Potentials

Iron (Fe) and copper (Cu), essential transition metals, play pivotal roles in various cellular processes critical to cancer biology, including cell proliferation, mitochondrial respiration, distant metastases, and oxidative stress. The emergence of ferroptosis and cuproptosis as distinct forms of non-apoptotic cell death has heightened their significance, particularly in connection with these metal ions. While initially studied separately, recent evidence underscores the interdependence of ferroptosis and cuproptosis. Studies reveal a link between mitochondrial copper accumulation and ferroptosis induction. This interconnected relationship presents a promising strategy, especially for addressing refractory cancers marked by drug tolerance. Harnessing the toxicity of iron and copper in clinical settings becomes crucial. Simultaneous targeting of ferroptosis and cuproptosis, exemplified by the combination of sorafenib and elesclomol-Cu, represents an intriguing approach. Strategies targeting mitochondria further enhance the precision of these approaches, providing hope for improving treatment outcomes of drug-resistant cancers. Moreover, the combination of iron chelators and copper-lowering agents with established therapeutic modalities exhibits a synergy that holds promise for the augmentation of anti-tumor efficacy in various malignancies. This review elaborates on the complex interplay between ferroptosis and cuproptosis, including their underlying mechanisms, and explores their potential as druggable targets in both cancer research and clinical settings.

Mandatory fortification of rice in the public distribution system in India: An ethics perspective.

In response to the continuing high prevalence of anaemia recorded in the National Family Health Survey-5, the Indian government launched a policy for mandatory iron fortification of the rice provided through public nutrition programmes in India. This was done even though a rigorous evidence analysis had already concluded that rice fortification was not effective in preventing anaemia or iron deficiency at the population level. Fortification also poses a potential risk of iron toxicity over time, but there is no stated time period for the policy's implementation. The risk is particularly high in segments of the population who already have a high habitual iron intake, and who could be exposed to simultaneous fortification in different staples and food commodities along with the ongoing weekly Iron and Folic Acid tablets supplementation programme. Finally, this fortification policy also requires significant additional funding and resources to implement. It is crucial to examine such mandatory health actions, and to weigh the benefits and risks of harm, using the principles of public health ethics.

Humate-Silica as an ameliorant to decrease Fe toxicity and increase rice yields on acid sulfate soils

Iron toxicity is a major problem in increasing rice production in acid-sulfate soils. Humate materials and Silica ions can interact with Fe ions to form chelates so that they can decrease Fe toxicity and increase rice yields. This research aimed to study the effect of humate-silica soil on decreasing Fe toxicity and increasing rice yields in acid-sulfate soils. The research employed a simple randomized block design incorporating treatments F0=100% lime, F1=30% humate manufacturer+30% rice husk ash+40% lime, F2=30% water hyacinth humate+30% rice husk ash+40% lime, F3=30% water hyacinth humate+30% rice husk biochar + 40% lime, F4=30% humate manufacturer+30% rice husk biochar+40% lime, and control=without ameliorant. Each treatment was repeated 4 times. Observations of soil characteristics were carried out at the end vegetative stage including pH and Fe, while at the end of the research, observed including panicle length, 100g weight, and grain weight per pot. The findings indicated that F1 was able to increase pH and decrease Fe2+ concentration and wasn’t significantly different from F3. Ameliorant F3 was able to decrease Fe toxicity and increase rice yields. The application of this formula resulted in a decrease in the usage of agricultural lime while enhancing rice productivity in tidal soil.

Iron toxicity, ferroptosis and microbiota in Parkinson's disease: Implications for novel targets.

Parkinson's Disease (PD) is a progressive neurodegenerative disease characterized by loss of dopaminergic neurons in substantia nigra pars compacta (SNpc). Iron (Fe)-dependent programmed cell death known as ferroptosis, plays a crucial role in the etiology and progression of PD. Since SNpc is particularly vulnerable to Fe toxicity, a central role for ferroptosis in the etiology and progression of PD is envisioned. Ferroptosis, characterized by reactive oxygen species (ROS)-dependent accumulation of lipid peroxides, is tightly regulated by a variety of intracellular metabolic processes. Moreover, the recently characterized bi-directional interactions between ferroptosis and the gut microbiota, not only provides another window into the mechanistic underpinnings of PD but could also suggest novel interventions in this devastating disease. Here, following a brief discussion of PD, we focus on how our expanding knowledge of Fe-induced ferroptosis and its interaction with the gut microbiota may contribute to the pathophysiology of PD and how this knowledge may be exploited to provide novel interventions in PD.

Bacterial toxicity of sulfidated nanoscale zerovalent iron in aerobic and anaerobic systems: implications for chlorinated solvent clean-up strategies

Abstract Sulfidated nanoscale zerovalent iron (S-nZVI) materials show enhanced reactivity and selectivity towards chlorinated solvents compared to non-sulfidated nZVI, thus they have a high potential for subsurface chlorinated solvent remediation. However, little is known about the possible toxic effects of S-nZVI towards microbial communities, which is of particular concern with regard to combined abiotic–biotic chlorinated solvent treatment scenarios. In this study, the toxicity of two different S-nZVI materials towards Shewanella oneidensis MR-1 (S. MR-1) was examined under anaerobic and aerobic conditions using colony forming units (CFU) and adenosine triphosphate (ATP) measurements, and the results were then compared to identical exposures performed with non-sulfidated nZVI. In a second step, the toxicity of S-nZVI and nZVI materials was tested on the commercial bioremediation culture KB-1® and on an in-house trichloroethylene enrichment culture. Under aerobic conditions, S. MR-1 viability was less affected by S-nZVI materials compared to non-sulfidated nZVI materials (up to three times higher viability) and it was generally lower compared to anaerobic conditions where little difference in S. MR-1 viability was observed between the tested materials. In terms of the two dechlorinating cultures, they exhibited significantly higher ATP viability during anaerobic exposures to S-nZVI and nZVI materials. Particularly for KB-1®, which retained comparable ATP-viability after ~60 hours exposure as S. MR-1 after two hours. Moreover, the ATP viability of the mixed cultures was generally higher in S-nZVI exposures compared to nZVI exposures (up to three times higher viability). The observed viability patterns are explained by differences in the shell structure, chemistry and stability of the tested S-nZVI and nZVI materials towards corrosion, while the substantially enhanced resilience of KB-1® is argued to stem from its year-long cultivation in the presence of reduced FeS particulates.

Iron toxicity effects on the growth and biochemical analysis of Lady’s finger (Abelmoschus esculentus) plants

Iron toxicity effects on the growth and biochemical analysis of Lady’s finger (Abelmoschus esculentus) plants

Improvement of Rice Plant Root by Kaolin Application in Iron Toxicity Condition at Zoukougbeu (Central-West of Côte d’Ivoire)

Improvement of Rice Plant Root by Kaolin Application in Iron Toxicity Condition at Zoukougbeu (Central-West of Côte d’Ivoire)

Mitigating Iron Toxicity by Using Rock Phosphate to Improve Rice Productivity

Mitigating Iron Toxicity by Using Rock Phosphate to Improve Rice Productivity

The induction of metallothionein by sulforaphane reduces iron toxicity via Nrf2

The induction of metallothionein by sulforaphane reduces iron toxicity via Nrf2

Subconjunctival deferoxamine for corneal rust deposits associated with ocular siderosis: A case report

Introduction: Ocular siderosis is a vision-threatening condition resulting from intraocular iron toxicity. This case re-establishes a role for subconjunctival deferoxamine, a chelating agent uncommonly used in ophthalmology, as an adjunctive treatment for ocular siderosis. Case Report: A 37-year-old healthy male presented two months after an injury at work with intermittent pain and blurry vision in the right eye. Presenting visual acuity (VA) was 20/100 in the right eye. With delayed presentation, the patient already had ocular siderosis with corneal rust deposits and retinal damage. The patient underwent pars plana vitrectomy (PPV) with surgical view impaired by corneal deposits and intraocular metallic intraocular foreign body (IOFB) that disintegrated upon attempted removal. At six months postoperatively, VA was 20/70 in the right eye, and examination revealed worsened diffuse, pigmented subepithelial deposits in the central cornea, iris atrophy, cotton wool spots, optic nerve pallor, and a residual IOFB in the anterior vitreous, consistent with worsened ocular siderosis. Superficial keratectomy was performed in combination with repeat PPV to improve surgical visualization and aid in IOFB removal. An amniotic membrane was placed and a subconjunctival injection of deferoxamine was administered. The cornea was well-healed with significantly improved siderosis and no epithelial defects on 2-week postoperative follow-up. Visual acuity was 20/60 at last follow-up two months postoperatively after second surgery. Conclusion: In treating ocular siderosis, subconjunctival injection of deferoxamine can be a useful addition to surgical IOFB removal to prevent the accumulation of iron deposits in the anterior segment of the eye.

Dumbbell-like Au–Fe3O4 nanoparticles for magnetic hyperthermia

Dumbbell-shaped hybrid nanoparticles, consisting of gold and iron oxide (Au-Fe3O4 NPs), show promise for magnetic hyperthermia cancer therapy. However, conventional synthesis methods using toxic iron pentacarbonyl (Fe(CO)5) raise safety concerns. We propose a safer approach using triiron dodecacarbonyl (Fe3(CO)12) as a precursor. We synthesize these NPs by initially reducing gold (III) chloride trihydrate with a tert-butylamine-borane complex at room temperature, yielding Au NPs. These Au NPs are combined with a Fe3(CO)12 solution and heated to 300 °C for 1 hour, resulting in the desired dumbbell-shaped Au-Fe3O4 NPs. Characterization confirms their morphology, with average sizes of 5 nm for Au NPs and 15 nm for Fe3O4 NPs. Our systematic evaluation of hydrophilic-treated Au-Fe3O4 NPs (Ms=49.5 emu/g at 3T, 300K) demonstrates temperature increases beyond the therapeutic threshold of 45 °C (ΔT=8 °C) at higher field strengths (8.6–30.0 kA/m), highlighting their cancer treatment potential. Quantitative analysis reveals superb performance, with a specific absorption rate (SAR) of 60.0 W/g and intrinsic loss power (ILP) of 0.25 nHm2kg−1 at the maximum field strength. These findings emphasize the significant potential of our dumbbell-shaped Au–Fe3O4 NPs for magnetic hyperthermia.

Characterization of New Rice Genotypes for Blast and Brown Spot Disease Resistance and Iron-Toxicity Tolerance in Burkina Faso

Rice production in Burkina Faso is threatened by a number of abiotic and biotic constraints, including iron toxicity and main fungal diseases that limit the potential of cultivated varieties. The general objective of this study was to evaluate the performance of new rice genotypes against main biotic and abiotic stresses. A total of 08 genotypes were tested allowed a Fisher block design with 03 replicates. Assessments focused on severity of iron toxicity, the severity and incidence of blast and brown spot disease and agro-morphological traits. The GRS IR-6-S3-Y1-D genotype was the most sensitive to iron toxicity, while the Sahel 108, BF19AR006 and SV1CP genotypes were the most resistant. As for fungal diseases, severity scores ranged from 4.33 to 7.67 for blast and from 4.00 to 7.03 for brown spot disease while incidence rates were 88.33% and 81.67% for blast and brown spot disease respectively. Genotype IR93654-10-3-2-1-ARS-SALS was resistant to both blast and brown spot disease. Person's correlation matrix showed both positive and negative correlations between the various agro-morphological parameters and pathological traits. Hierarchical ascending classification showed that the SV1CP and IR93654-10-3-2-1-ARS-SALS genotypes performed better agronomically. with yields of over 7.000 kg/ha and showed good tolerance to iron toxicity, blast and brown spot disease.

Evaluation the Non enzymatic antioxidants in patients with β-thalassemia major among Iraqi patients

Background: β-thalassemia major (β-TM) is a major health problem in the world that forces patients to repeat blood transfusions. Frequent blood transfusions cause toxic iron overload. The association between serum iron levels and β-thalassemia major has been studied extensively in the literature. Several studies have evaluated the oxidant and antioxidant statuses of thalassemia patients. However, most studies have focused mainly on the enzymatic antioxidant and intermediate states and thus few data are available for non-enzymatic antioxidant like Coenzyme Q10. aim of study: To evaluate the concentration of some non- enzymatic antioxidant measurements like Coenzyme Q10, Vitamin C, Vitamin E, uric acid, and bilirubin in the plasma of patients who suffered from beta – thalassemia major. Patients and Methods: Case- control study designed includes 90 participating (60 β-TM patients and 30 subjects as control groups). The age range of patients and control group was (15 - 40 years). This study was conducted in Teaching Baghdad Hospital - Baghdad and Al-Karama Hospital during the period from December 2022 to March 2023. Results: The mean of serum Coenzyme Q10 was (3.55 ± 1.62 and 2.02 ± 0.88 ng/ml) in β-TM patients and control group respectively. The results reveled that the mean of vitamin C was (6.85 ± 3.0 and 12.23 ± 2.99 ng/ml) in β-TM and control group respectively. Also, the results shows that the mean of Vitamin E was (2.29 ± 1.69 and 7.25 ± 2.79 ng/ml) in β-TM patients and control respectively. Also, the results reveled that mean of uric acid was (3.62 ± 1.34 and 3.86 ± 1.48 mg/dl) in β-TM patients and control group respectively. The level of bilirubin was (1.99 ± 1.25 and 0.65 ± 0.6 mg/dl) in patients and control group respectively. Also, the result shows there was a significant correlation between Coenzyme Q10 and Vitamin C ((r=0.280, p=0.030) and non-significant correlation between Coenzyme Q10 and Vitamin E (r=0.084, p=0.522). Conclusion: This study shows there were lower antioxidant capacities as demonstrated by the results in patients with β-TM patients in comparison with control group.

The Effect of Oral Iron Chelator Deferiprone on Iron Overload and Oxidative Stress in Patients with Myelodysplastic Syndromes: A Study by the Israeli MDS Working Group

Background: Most patients with lower risk myelodysplastic neoplasms or syndromes (MDSs) become RBC transfusion-dependent, resulting in iron overload, which is associated with an increased oxidative stress state. Iron-chelation therapy is applied to attenuate the toxic effects of this state. Deferiprone (DFP) is an oral iron chelator, which is not commonly used in this patient population, due to safety concerns, mainly agranulocytosis. The purpose of this study was to assess the effect of DFP, on oxidative stress parameters in iron-overloaded RBC transfusion-dependent patients with lower risk MDSs. Methods: Adult lower risk MDS patients with a cumulative transfusion burden of >20 red blood cell units and evidence of iron overload (serum ferritin >1,000 ng/mL) were included in this study. DFP was administered (100 mg/kg/day) for 4 months. Blood samples for oxidative stress parameters and iron overload parameters were done at baseline and monthly: reactive oxygen species (ROS), phosphatidylserine, reduced glutathione, membrane lipid peroxidation, serum ferritin, and cellular labile iron pool. The primary efficacy variable was ROS. Tolerability and side effects were recorded as well. A paired t test was applied for statistical analyses. Results: Eighteen patients were treated with DFP. ROS significantly decreased in all cell lineages: median decrease of 58.6% in RBC, 33.3% in PMN, and 39.8% in platelets (p < 0.01 for all). Other oxidative stress markers improved: phosphatidylserine decreased by 57.95%, lipid peroxidase decreased by 141.3%, and reduced gluthathione increased by 72.8% (p < 0.01 for all). The iron-overload marker and cellular labile iron pool decreased by 35% in RBCs, 44.3% in PMN, and 46.3% in platelets (p < 0.01 for all). No significant changes were observed in SF levels. There were no events of agranulocytosis. All AEs were grades 1–2. Conclusions: Herein, we showed preliminary evidence that DFP decreases iron-induced oxidative stress in MDS patients with a good tolerability profile (albeit a short follow-up period). No cases of severe neutropenia or agranulocytosis were reported. The future challenge is to prove that reduction in iron toxicity will eventually be translated into a clinically meaningful improvement.

Hydrogen Attenuates Chronic Intermittent Hypoxia-Induced Cardiac Hypertrophy by Regulating Iron Metabolism.

The present study aimed to investigate the impact of hydrogen (H2) on chronic intermittent hypoxia (CIH)-induced cardiac hypertrophy in mice by modulating iron metabolism. C57BL/6N mice were randomly allocated into four groups: control (Con), CIH, CIH + H2, and H2. The mice were exposed to CIH (21-5% FiO2, 3 min/cycle, 8 h/d), and received inhalation of a hydrogen-oxygen mixture (2 h/d) for 5 weeks. Cardiac and mitochondrial function, levels of reactive oxygen species (ROS), and iron levels were evaluated. The H9C2 cell line was subjected to intermittent hypoxia (IH) and treated with H2. Firstly, we found H2 had a notable impact on cardiac hypertrophy, ameliorated pathological alterations and mitochondrial morphology induced by CIH (p < 0.05). Secondly, H2 exhibited a suppressive effect on oxidative injury by decreasing levels of inducible nitric oxide synthase (i-NOS) (p < 0.05) and 4-hydroxynonenal (4-HNE) (p < 0.01). Thirdly, H2 demonstrated a significant reduction in iron levels within myocardial cells through the upregulation of ferroportin 1 (FPN1) proteins (p < 0.01) and the downregulation of transferrin receptor 1 (TfR1), divalent metal transporter 1 with iron-responsive element (DMT1(+ire)), and ferritin light chain (FTL) mRNA or proteins (p < 0.05). Simultaneously, H2 exhibited the ability to decrease the levels of Fe2+ and ROS in H9C2 cells exposed to IH (p < 0.05). Moreover, H2 mediated the expression of hepcidin, hypoxia-inducible factor-1α (HIF-1α) (p < 0.01), and iron regulatory proteins (IRPs), which might be involved in the regulation of iron-related transporter proteins. These results suggested that H2 may be beneficial in preventing cardiac hypertrophy, a condition associated with reduced iron toxicity.