Tissue Iron Content Research Articles

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.

Development of a Predictive Model for Iron Levels in Bovine Muscle Tissue Using Hair as a Predictor.

The assessment of iron levels in cattle muscle tissue is crucial for livestock management because it influences both animal health and meat quality, key factors in sustainable development. This study aimed to develop an optimal model for noninvasively predicting the iron content in Hereford cattle muscle tissue, contributing to a comprehensive understanding of the animals' elemental status. The research involved the atomic absorption analysis of muscle tissue and hair samples from cattle. A regression model was constructed using the least squares method to identify the most effective approach. These findings have ecological applications, aiding in evaluating environmental health and establishing acceptable iron thresholds for animals. The proposed mathematical model utilizing biomarkers (levels of Mg, K, Fe, Al, Cr in hair) will allow for the assessment of iron levels in cattle muscle tissue throughout the period of productive use, with the possibility of adjustment and tracking the changes in elemental status over time. The utilization of the developed method will enable the diagnosis of animal elementosis and assessment of the iron level burden. Subsequently, this will allow for the improvement of the qualitative characteristics of the final product. Thus, the obtained data contribute to fundamental knowledge regarding the content and variability of iron levels in the muscle tissue of cattle.

Simvastatin-Mediated Nrf2 Activation Induces Fetal Hemoglobin and Antioxidant Enzyme Expression to Ameliorate the Phenotype of Sickle Cell Disease.

Sickle cell disease (SCD) is a pathophysiological condition of chronic hemolysis, oxidative stress, and elevated inflammation. The transcription factor Nrf2 is a master regulator of oxidative stress. Here, we report that the FDA-approved oral agent simvastatin, an inhibitor of hydroxymethyl-glutaryl coenzyme A reductase, significantly activates the expression of Nrf2 and antioxidant enzymes. Simvastatin also induces fetal hemoglobin expression in SCD patient primary erythroid progenitors and a transgenic mouse model. Simvastatin alleviates SCD symptoms by decreasing hemoglobin S sickling, oxidative stress, and inflammatory stress in erythroblasts. Particularly, simvastatin increases cellular levels of cystine, the precursor for the biosynthesis of the antioxidant reduced glutathione, and decreases the iron content in SCD mouse spleen and liver tissues. Mechanistic studies suggest that simvastatin suppresses the expression of the critical histone methyltransferase enhancer of zeste homolog 2 to reduce both global and gene-specific histone H3 lysine 27 trimethylation. These chromatin structural changes promote the assembly of transcription complexes to fetal γ-globin and antioxidant gene regulatory regions in an antioxidant response element-dependent manner. In summary, our findings suggest that simvastatin activates fetal hemoglobin and antioxidant protein expression, modulates iron and cystine/reduced glutathione levels to improve the phenotype of SCD, and represents a therapeutic strategy for further development.

Uptake and bioaccumulation of iron oxide nanoparticles (Fe3O4) in barley (Hordeum vulgare L.): effect of particle-size.

Root-to-shoot translocation of nanoparticles (NPs) is a matter of interest due to their possible unprecedented effects on biota. Properties of NPs, such as structure, surface charge or coating, and size, determine their uptake by cells. This study investigates the size effect of iron oxide (Fe3O4) NPs on plant uptake, translocation, and physiology. For this purpose, Fe3O4 NPs having about 10 and 100 nm in average sizes (namely NP10 and NP100) were hydroponically subjected to barley (Hordeum vulgare L.) in different doses (50, 100, and 200 mg/L) at germination (5 days) and seedling (3 weeks) stages. Results revealed that particle size does not significantly influence the seedlings' growth but improves germination. The iron content in root and leaf tissues gradually increased with increasing NP10 and NP100 concentrations, revealing their root-to-shoot translocation. This result was confirmed by vibrating sample magnetometry analysis, where the magnetic signals increased with increasing NP doses. The translocation of NPs enhanced chlorophyll and carotenoid contents, suggesting their contribution to plant pigmentation. On the other hand, catalase activity and H2O2 production were higher in NP10-treated roots compared to NP100-treated ones. Besides, confocal microscopy revealed that NP10 leads to cell membrane damages. These findings showed that Fe3O4 NPs were efficiently taken up by the roots and transported to the leaves regardless of the size factor. However, small-sized Fe3O4 NPs may be more reactive due to their size properties and may cause cell stress and membrane damage. This study may help us better understand the size effect of NPs in nanoparticle-plant interaction.

Imaging of Endometriotic Lesions Using cRGD-MN Probe in a Mouse Model of Endometriosis

Approximately 10% of women suffer from endometriosis during their reproductive years. This disease is a chronic debilitating condition whose etiology for lesion implantation and survival heavily relies on adhesion and angiogenic factors. Currently, there are no clinically approved agents for its detection. In this study, we evaluated cRGD-peptide-conjugated nanoparticles (RGD-Cy5.5-MN) to detect lesions using magnetic resonance imaging (MRI) in a mouse model of endometriosis. We utilized a luciferase-expressing murine suture model of endometriosis. Imaging was performed before and after 24 h following the intravenous injection of RGD-Cy5.5-MN or control nanoparticles (Cy5.5-MN). Next, we performed biodistribution of RGD-Cy5.5-MN and correlative fluorescence microscopy of lesions stained for CD34. Tissue iron content was determined using inductively coupled plasma optical emission spectrometry (ICP-OES). Our results demonstrated that targeting endometriotic lesions with RGD-Cy5.5-MN resulted in a significantly higher delta T2* upon its accumulation compared to Cy5.5-MN. ICP-OES showed significantly higher iron content in the lesions of the animals in the experimental group compared to the lesions of the animals in the control group. Histology showed colocalization of Cy5.5 signal from RGD-Cy5.5-MN with CD34 in the lesions pointing to the targeted nature of the probe. This work offers initial proof-of-concept for targeting angiogenesis in endometriosis which can be useful for potential clinical diagnostic and therapeutic approaches for treating this disease.

Excessive dietary iron exposure increases the susceptibility of largemouth bass (Micropterus salmoides) to Aeromonas hydrophila by interfering with immune response, oxidative stress, and intestinal homeostasis

Iron is an essential cofactor in the fundamental metabolic pathways of organisms. Moderate iron intake can enhance animal growth performance, while iron overload increases the risk of pathogen infection. Although the impact of iron on the pathogen-host relationship has been confirmed in higher vertebrates, research in fish is extremely limited. The effects and mechanisms of different levels of iron exposure on the infection of Aeromonas hydrophila in largemouth bass (Micropterus salmoides) remain unclear. In this study, experimental diets were prepared by adding 0, 800, 1600, and 3200 mg/kg of FeSO4∙7H2O to the basal feed, and the impact of a 56-day feeding period on the mortality rate of largemouth bass infected with A. hydrophila was analyzed. Additionally, the relationships between mortality rate and tissue iron content, immune regulation, oxidative stress, iron homeostasis, gut microbiota, and tissue morphology were investigated. The results showed that the survival rate of largemouth bass infected with A. hydrophila decreased with increasing iron exposure levels. Excessive dietary iron intake significantly increased iron deposition in the tissues of largemouth bass, reduced the expression and activity of antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase, increased the content of lipid peroxidation product malondialdehyde, and thereby induced oxidative stress. Excessive iron supplementation could influence the immune response of largemouth bass by upregulating the expression of pro-inflammatory cytokines in the intestine and liver, while downregulating the expression of anti-inflammatory cytokines. Additionally, excessive iron intake could also affect iron metabolism by inducing the expression of hepcidin, disrupt intestinal homeostasis by interfering with the composition and function of the gut microbiota, and induce damage in the intestinal and hepatic tissues. These research findings provide a partial theoretical basis for deciphering the molecular mechanisms underlying the influence of excessive iron exposure on the susceptibility of largemouth bass to pathogenic bacteria.

Cadmium Induces Kidney Iron Deficiency and Chronic Kidney Injury by Interfering with the Iron Metabolism in Rats.

Cadmium (Cd) is a common environmental pollutant and occupational toxicant that seriously affects various mammalian organs, especially the kidney. Iron ion is an essential trace element in the body, and the disorder of iron metabolism is involved in the development of multiple pathological processes. An iron overload can induce a new type of cell death, defined as ferroptosis. However, whether iron metabolism is abnormal in Cd-induced nephrotoxicity and the role of ferroptosis in Cd-induced nephrotoxicity need to be further elucidated. Sprague Dawley male rats were randomly assigned into three groups: a control group, a 50 mg/L CdCl2-treated group, and a 75 mg/L CdCl2-treated group by drinking water for 1 month and 6 months, respectively. The results showed that Cd could induce renal histopathological abnormalities and dysfunction, disrupt the mitochondria's ultrastructure, and increase the ROS and MDA content. Next, Cd exposure caused GSH/GPX4 axis blockade, increased FTH1 and COX2 expression, decreased ACSL4 expression, and significantly decreased the iron content in proximal tubular cells or kidney tissues. Further study showed that the expression of iron absorption-related genes SLC11A2, CUBN, LRP2, SLC39A14, and SLC39A8 decreased in proximal tubular cells or kidneys after Cd exposure, while TFRC and iron export-related gene SLC40A1 did not change significantly. Moreover, Cd exposure increased SLC11A2 gene expression and decreased SLC40A1 gene expression in the duodenum. Finally, NAC or Fer-1 partially alleviated Cd-induced proximal tubular cell damage, while DFO and Erastin further aggravated Cd-induced cell damage. In conclusion, our results indicated that Cd could cause iron deficiency and chronic kidney injury by interfering with the iron metabolism rather than typical ferroptosis. Our findings suggest that an abnormal iron metabolism may contribute to Cd-induced nephrotoxicity, providing a novel approach to preventing kidney disease in clinical practice.

Ferroptosis is involved in focal segmental glomerulosclerosis in rats

To explore whether ferroptosis is involved in focal segmental glomerulosclerosis (FSGS) and its mechanism. The FSGS rat model was constructed by single nephrectomy combined with fractional tail vein injection of doxorubicin. 24-hour urine protein, serum biochemistry, HE, PAS and Masson pathological staining were measured to assess renal injury. Glomerular and morphological changes of ferroptosis were observed by transmission electron microscopy. Iron content in renal tissue was assessed by Prussian blue staining and iron detection. GSH/GSSG kit was used to detect the content and proportion of reduced/oxidized glutathione. Lipid peroxidation related proteins including MDA expression was assessed by colorimetry. The iron metabolism biomarkers such as hepcidin, ferroportin and TFR, ferroptosis biomarkers such as GPX4, ACSL4, and ferritinophagy biomarkers such as LC3II/LC3I, NCOA4, and FTH1 were detected by Western blot. Significant urinary protein, hyperlipidemia, azotemia, increased serum creatinine and hypoproteinemia were observed in FSGS rats. Histology and electron microscopy showed segmental sclerosis of glomeruli, compensatory enlargement of some glomeruli, occlusion of capillary lumen, balloon adhesion, increased mesangial matrix, atrophy of some tubules, and renal interstitial fibrosis in renal tissue of FSGS rats. The morphology of glomerular foot processes disappeared; the foot processes were extensively fused and some foot processes detached. Mitochondria became smaller, membrane density increased, and mitochondrial cristae decreased or disappeared. In addition, iron deposition was observed in renal tissue of FSGS rats. Compared with the control group, the levels of GSH, GSH/GSSG, GPX4, and ferroportin were reduced and the expression of GSSG, MDA, ACSL4, hepcidin, and TFR was increased in the renal tissue of FSGS rats; meanwhile, the expression of LC3II/LC3I and NCOA4 was increased and the expression of FTH1 was decreased. Ferroptosis is involved in the pathological progression of FSGS, which is probably associated with activation of ferritinophagy. This represents a potential therapeutic target for FSGS.

Comparison of three magnetic resonance imaging measures of brain iron in healthy and cocaine use disorder participants.

Several magnetic resonance imaging (MRI) measures for quantifying endogenous nonheme brain iron have been proposed. These correspond to distinct physical properties with varying sensitivities and specificities to iron. Moreover, they may depend not only on tissue iron concentration, but also on the intravoxel spatial pattern of iron deposition, which is complex in many brain regions. Here, the three MRI brain iron measures of , magnetic field correlation (MFC), and magnetic susceptibility are compared in several deep gray matter regions for both healthy participants (HPs) and individuals with cocaine use disorder (CUD). Their concordance is assessed from their correlations with each other and their relative dependencies on age. In addition, associations between the iron measures and microstructure in adjacent white matter regions are investigated by calculating their correlations with diffusion MRI measures from the internal capsule, and associations with cognition are determined by using results from a battery of standardized tests relevant to CUD. It is found that all three iron measures are strongly correlated with each other for the considered gray matter regions, but with correlation coefficients substantially less than one indicating important differences. The age dependencies of all three measures are qualitatively similar in most regions, except for the red nucleus, where the susceptibility has a significantly stronger correlation with age than . Weak to moderate correlations are seen for the iron measures with several of the diffusion and cognitive measures, with the strongest correlations being obtained for . The iron measures differ little between the HP and CUD groups, although susceptibility is significantly lower in the red nucleus for the CUD group. For the comparisons made, the iron measures behave similarly in most respects, but with notable quantitative differences. It is suggested that these differences may be, in part, attributable to a higher sensitivity to the spatial pattern of iron deposition for and MFC than for susceptibility. This is supported most strongly by a sharp contrast between the values of the iron measures in the globus pallidus relative to those in the red nucleus. The observed correlations of the iron measures with diffusion and cognitive scores point to possible connections between gray matter iron, white matter microstructure, and cognition.

113 Effect of Birth Weight on Tissue Copper, Iron, and Zinc Concentrations in Piglets

Abstract Pigs (n = 3,990) were used in a previous study to determine if supplemental zinc fed to sows at various timepoints during gestation would reduce pre-weaning mortality. Additionally, data were analyzed to evaluate the effect of birth weight on tissue concentrations and distribution of copper (Cu), iron (Fe), and zinc (Zn) in piglets. Mixed parity sows were fed 1 of 3 diets: a control corn-soybean meal diet containing 125 ppm supplemental Zn supplied by zinc hydroxychloride, a diet consisting of the control + 141 ppm supplemental Zn as ZnSO4 (266 ppm total supplemental Zn) fed from 5 days after breeding to farrowing, or the control diet fed from breeding to farrowing + 2,715 ppm of supplemental Zn from ZnSO4 (2,840 ppm total supplemental Zn) starting on day 110 of gestation until farrowing. Two low and 2 average birth weight pigs (n = 122) were selected from 10 sows per treatment group to assess Cu, Fe, and Zn concentrations of serum and tails. Serum was collected from each pig at day 1 of age and tails were collected on day 2 of age. Liver tissue was collected from a subset of pigs (n = 65) that died naturally or were euthanized within 2 days of age. The statistical model included fixed effects of treatment and farrowing group, the random effect of their interaction, and the random effect of pig nested within sow. Serum concentrations of each trace element did not differ by birth weight (Table). Low birth weight piglets had greater concentrations of Fe (P = 0.018) and Cu (P = 0.031) in their tails than average birth weight pigs. No differences were observed in tail Zn concentration by birth weight. Notably, pigs that died naturally weighed less at birth than euthanized pigs (P < 0.001). Moreover, pigs that died naturally had greater hepatic Fe concentrations (P < 0.001) and tended to have greater liver Cu concentrations (P = 0.098) compared with euthanized pigs. The associations between tissue iron and copper concentrations and birth weight of piglets may have nutritional and pathophysiological implications and thus warrant further investigation.

Zinc nanoparticles ameliorated obesity-induced cardiovascular disease: role of metabolic syndrome and iron overload

Obesity is a complicated disease characterized by abundant fat accumulation. It is associated with cardiovascular disease. The current study aimed to appreciate the role of synthesized zinc oxide nanoparticles (ZnONPs) (18.72 nm in size) in curbing cardiovascular disease in an obesity model of a high fat/sucrose diet in male rats. For 16 weeks, 24 rats were fed a high-fat diet and a 25% sucrose solution to develop obesity, and after that, the rats were randomly allocated into four groups of rats. Group 1 served as the control group and consisted of normal, non-obese rats. Group 2 comprised obese rats that were injected with an equivalent volume of a neutral substance, serving as vehicle control. In Group 3 or 4, obese rats were treated with an intraperitoneal injection of 5 or 10mg/kg of zinc oxide nanoparticles (ZnONPs) for eight weeks. The treatment of obese rats with ZnONPs decreased plasma levels of monocyte chemoattractant Protein-1 (MCP-1), resistin, ENA78, tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL6), and C reactive protein (CRP). Also, the remediation of obese rats with ZnONPs led to a significant decrease in body mass index (BMI), body weight gain, leptin, cholesterol, triglycerides, LDL (Low-density lipoprotein), glucose, and insulin resistance index (HOMA-IR). Moreover, ZnONPs treatment lowered troponin, creatine phosphokinase-MB (CK-MB), lactate dehydrogenase (LDH), cardiac or adipose tissue iron content, and malondialdehyde (MDA) either in blood or heart tissue. Otherwise, treating obese rats with ZnONPs enhanced plasma adiponectin levels, cardiac-reduced glutathione (GSH), and superoxide dismutase (SOD). In addition, ZnONPs displayed a significant influence on the cardiovascular system since they combat the rise in blood pressure and the pathological changes of the heart and aorta besides maintaining plasma nitric oxide levels. The results showed a positive correlation between BMI and MDA, MPC-1, CK-MB, and LDH. ZnONPs are convenient in treating cardiovascular disease in obese rats via reduced blood pressure, oxidative stress, cardiac iron accumulation, insulin resistance, and inflammatory markers.

Suberosin Alleviates Thiazolidinedione-Induced Cardiomyopathy in Diabetic Rats by Inhibiting Ferroptosis via Modulation of ACSL4-LPCAT3 and PI3K-AKT Signaling Pathways.

Thiazolidinediones are useful antidiabetic medications. However, their use is associated with adverse side effects like edema, heart failure and bone fractures. In this study, we investigated the anti-ferroptosis effects of suberosin (SBR; a prenylated coumarin) in diabetic Sprague Dawley rats. Further, we assessed the effects of co-administration of SBR (30 and 90mg/kg/day) with thiazolidinedione (TZ at 15mg/kg) to mitigate TZ-induced cardiomyopathy in diabetic rats. Our results showed that cardiac output, stroke volume, left ventricle systolic and diastolic pressures were aggravated in diabetic rats treated with TZ alone after 4weeks. TZ treatments induced ferroptosis as well as marked histoarchitecture disarrangements in rat cardiomyocytes. The study found that optimizing volume overload alleviated cardiac hypertrophy and mitigated left ventricular dysfunction in diabetic rats co-treated with SBR. SBR co-administration with TZ reduced MDA levels in heart tissue and serum iron concentration (biomarkers of ferroptosis), downregulated mRNA expressions of LOX, ACSL4, LPCAT3, and promoted GPX4 activity as well as upregulated mRNA levels of AKT/PI3K/GSK3β as compared to the group administered with TZ at 15mg/kg. SBR co-administration also helped to retain the normal histoarchitecture of cardiomyocytes in diabetic rats. Hence, our results suggested that SBR is an effective supplement and could be prescribed to diabetic patients along with TZ but this requires further clinical trials.

Raynaud phenomenon and microvasculopathy in systemic sclerosis: multi-modality imaging for diagnosis and evaluation.

To describe the clinical significance of and the diagnostic approach to Raynaud phenomenon (RP) in the peripheral extremities and the heart. Nailfold capillaroscopy has recently been standardized in an expert consensus paper. Abnormal capillaroscopy in combination with specific autoantibody profiles and clinical signs are highly predictive of progression of RP to systemic sclerosis (SSc). Magnetic resonance imaging (MRI) can also perform tissue characterization of both the extremities and the heart. Microvascular wall abnormalities detected using nailfold capillaroscopy in patients with SSc may lead to deposition of erythrocyte-derived iron, due to microhemorrhages, which may predispose to fibrosis. MRI can assess the presence of iron using T2∗ measurements. RP is a hallmark of the microvasculopathy in SSc and can affect both the peripheral extremities and the heart. Nailfold capillaroscopy is the current gold standard for the evaluation of the peripheral microvasculature. Other imaging modalities include thermography, laser Doppler-derived methods, 99mTc-pertechnetate hand perfusion scintigraphy, power Doppler ultrasonography, dynamic optical coherence tomography, MRI, and photoacoustic imaging, but these are currently not widely used. Cardiac RP can be investigated with positron emission tomography or cardiovascular magnetic resonance, with the latter offering the additional possibility of tissue characterization and iron content quantification secondary to microhemorrhages.

Hydroxysafflor Yellow A Alleviates Acute Myocardial Ischemia/Reperfusion Injury in Mice by Inhibiting Ferroptosis via the Activation of the HIF-1α/SLC7A11/GPX4 Signaling Pathway.

Ferroptosis is closely associated with the pathophysiology of myocardial ischemia. Hydroxysafflor yellow A (HSYA), the main active ingredient in the Chinese herbal medicine safflower, exerts significant protective effects against myocardial ischemia/reperfusion injury (MI/RI). The aim of this study was to investigate the protective effects of HSYA against MI/RI and identify the putative underlying mechanisms. An in vivo model of acute MI/RI was established in C57 mice. Subsequently, the effects of HSYA on myocardial tissue injury were evaluated by histology. Lipid peroxidation and myocardial injury marker contents in myocardial tissue and serum and iron contents in myocardial tissue were determined using biochemical assays. Mitochondrial damage was assessed using transmission electron microscopy. H9C2 cardiomyocytes were induced in vitro by oxygen-glucose deprivation/reoxygenation, and ferroptosis inducer erastin was administered to detect ferroptosis-related indicators, oxidative-stress-related indicators, and expressions of ferroptosis-related proteins and HIF-1α. In MI/RI model mice, HSYA reduced myocardial histopathological damage, ameliorated mitochondrial damage in myocardial cells, and decreased total cellular iron and ferrous ion contents in myocardial tissue. HSYA increased the protein levels of SLC7A11, HIF-1α, and GPX4 and mitigated erastin- or HIF-1α siRNA-induced damage in H9C2 cells. In summary, HSYA alleviated MI/RI by activating the HIF-1α/SLC7A11/GPX4 signaling pathway, thereby inhibiting ferroptosis.

Dyshomeostasis of Iron and Its Transporter Proteins in Cypermethrin-Induced Parkinson's Disease.

The etiology of Parkinson's disease (PD) is highly complex and is still indefinable. However, a number of studies have indicated the involvement of pesticides and transition metals. Copper, magnesium, iron, and zinc have emerged as important metal contributors. Exposure to pesticides causes an accumulation of transition metals in the substantia nigra (SN) region of the brain. The cypermethrin model of PD is characterized by mitochondrial dysfunction, autophagy impairment, oxidative stress, etc. However, the effect of cypermethrin on metal homeostasis is not yet explored. The study was designed to delineate the role of metals and their transporter proteins in cypermethrin-induced animal and cellular models of PD. The level of copper, magnesium, iron, and zinc was checked in the nigrostriatal tissue and serum by atomic absorption spectroscopy. Since cypermethrin consistently increased iron content in the nigrostriatal tissue and serum after 12weeks of exposure, the level of iron transporter proteins, such as divalent metal transporter-1 (DMT-1), ceruloplasmin, transferrin, ferroportin, and hepcidin, and their in silico interaction with cypermethrin were checked. 3,3'-Diaminobenzidine-enhanced Perl's staining showed an elevated number of iron-positive cells in the SN of cypermethrin-treated rats. Molecular docking studies revealed a strong binding affinity between cypermethrin and iron transporter protein receptors of humans and rats. Furthermore, cypermethrin increased the expression of DMT-1 and hepcidin while reducing the expression of transferrin, ceruloplasmin, and ferroportin in the nigrostriatal tissue and human neuroblastoma cells. These observations suggest that cypermethrin alters the expression of iron transporter proteins leading to iron dyshomeostasis, which could contribute to dopaminergic neurotoxicity.

The effect of gibberellic acid on wheat growth and nutrient uptake under combined stress of cerium, zinc and titanium dioxide nanoparticles

Nanoparticles (NPs) are released and dispersed in the environment because of increased manufacturing and use of nano products. NPs disturb the growth of plants depending upon types, exposure duration and plant species. The purpose of this research was to explore the role of gibberellic acid (GA) exposure through foliar route on wheat growth under alone or combined soil application of cerium oxide (CeO2), zinc oxide (ZnO), and titanium dioxide (TiO2) NPs. GA was foliar-applied (200 mg/L) on the wheat plants treated with individual and in all possible combination of the selected NPs. Explorations have revealed that the combination of NPs and GA worked well to enhance the plant growth and selected nutrient status than NPs alone. Furthermore, GA decreased the boosted antioxidant enzyme activities under the combination and individual NPs compared to the alone NPs treated plants, lowered the oxidative stress in wheat plants which provided the additional proof that GA decreased oxidative damage in plants. Combined NPs showed differential effects than individual NPs application irrespective of GA exposure which varied with NPs combination and studied parameters of plants. GA + NPs differentially affected the potassium, phosphorus, iron and manganese concentrations in wheat tissues than NPs alone treatments. Overall, GA can be applied when there is excess of NPs (either alone or in combination) in the growth medium to ensure the growth of crops. However, further studied are needed with other plant species and alone or combined use of different NPs under GA treatment before any final recommendation.

IMPACT OF SIDEROPHORE PRODUCING RHIZOBACTERIA ON GROWTH AND IRON CONTENT IN POTATO

Iron deficiency is a prevalent nutritional disorder that has a significant impact on a large population worldwide. Malnutrition can potentially be mitigated through the implementation of biofortification, a method aimed at enhancing the micronutrient content of staple food items. Plant growth promoting rhizobacteria (PGPR) possess the capacity to enhance the iron concentration in consumable plant tissues by enhancing its availability through various mechanisms. A controlled experiment was conducted to evaluate the capacity of five bacterial isolates (Z1, Z2, Z3, Z4, Z5, Z6) to promote plant growth and enhance the bioavailability of iron (Fe) in potato plants. The iron was administered via a solution that consisted of iron sulphate. The study's results demonstrate that the utilization of PGPR led to a notable enhancement in multiple growth parameters of the plants, encompassing plant height, root length, root fresh and dry weights, shoot fresh and dry weights, and iron content, in comparison to plants that did not undergo PGPR inoculation. The application of FeSO4 led to a significant increase in the concentration of Fe, with a respective rise of 100% and 173% observed in the grain and shoot, in comparison to the control group. The application of Plant Growth Promoting Rhizobacteria (PGPR) in combination with iron led to a substantial improvement in the levels of iron in both grain and shoot tissues. Specifically, there was a notable increase of 78.64% in grain iron content and a 63.24% increase in shoot iron content, as compared to the control group. The results of this study suggest that the utilization of plant growth-promoting rhizobacteria (PGPR) can augment the absorption of iron (Fe) by plants in the presence of supplementary Fe in the soil. The results of this study indicate that the implementation of microbial assisted biofortification in potato tuber holds promise for addressing micronutrient deficiency in human populations, particularly in regions with limited access to resources.

Liproxstatin-1 Alleviates Lung Transplantation-induced Cold Ischemia-Reperfusion Injury by Inhibiting Ferroptosis.

Primary graft dysfunction, which is directly related to cold ischemia-reperfusion (CI/R) injury, is a major obstacle in lung transplantation (LTx). Ferroptosis, a novel mode of cell death elicited by iron-dependent lipid peroxidation, has been implicated in ischemic events. This study aimed to investigate the role of ferroptosis in LTx-CI/R injury and the effectiveness of liproxstatin-1 (Lip-1), a ferroptosis inhibitor, in alleviating LTx-CI/R injury. LTx-CI/R-induced signal pathway alterations, tissue injury, cell death, inflammatory responses, and ferroptotic features were examined in human lung biopsies, the human bronchial epithelial (BEAS-2B) cells, and the mouse LTx-CI/R model (24-h CI/4-h R). The therapeutic efficacy of Lip-1 was explored and validated both in vitro and in vivo. In human lung tissues, LTx-CI/R activated ferroptosis-related signaling pathway, increased the tissue iron content and lipid peroxidation accumulation, and altered key protein (GPX4, COX2, Nrf2, and SLC7A11) expression and mitochondrial morphology. In BEAS-2B cells, the hallmarks of ferroptosis were significantly evidenced at the setting of both CI and CI/R compared with the control, and the effect of adding Lip-1 only during CI was much better than that of only during reperfusion by Cell Counting Kit-8. Furthermore, Lip-1 administration during CI markedly relieved LTx-CI/R injury in mice, as indicated by significant improvement in lung pathological changes, pulmonary function, inflammation, and ferroptosis. This study revealed the existence of ferroptosis in the pathophysiology of LTx-CI/R injury. Using Lip-1 to inhibit ferroptosis during CI could ameliorate LTx-CI/R injury, suggesting that Lip-1 administration might be proposed as a new strategy for organ preservation.

FoxO1 regulates adipose transdifferentiation and iron influx by mediating Tgfβ1 signaling pathway

Adipose plasticity is critical for metabolic homeostasis. Adipocyte transdifferentiation plays an important role in adipose plasticity, but the molecular mechanism of transdifferentiation remains incompletely understood. Here we show that the transcription factor FoxO1 regulates adipose transdifferentiation by mediating Tgfβ1 signaling pathway. Tgfβ1 treatment induced whitening phenotype in beige adipocytes, reducing UCP1 and mitochondrial capacity and enlarging lipid droplets. Deletion of adipose FoxO1 (adO1KO) dampened Tgfβ1 signaling by downregulating Tgfbr2 and Smad3 and induced browning of adipose tissue in mice, increasing UCP1 and mitochondrial content and activating metabolic pathways. Silencing FoxO1 also abolished the whitening effect of Tgfβ1 on beige adipocytes. The adO1KO mice exhibited a significantly higher energy expenditure, lower fat mass, and smaller adipocytes than the control mice. The browning phenotype in adO1KO mice was associated with an increased iron content in adipose tissue, concurrent with upregulation of proteins that facilitate iron uptake (DMT1 and TfR1) and iron import into mitochondria (Mfrn1). Analysis of hepatic and serum iron along with hepatic iron-regulatory proteins (ferritin and ferroportin) in the adO1KO mice revealed an adipose tissue-liver crosstalk that meets the increased iron requirement for adipose browning. The FoxO1-Tgfβ1 signaling cascade also underlay adipose browning induced by β3-AR agonist CL316243. Our study provides the first evidence of a FoxO1-Tgfβ1 axis in the regulation of adipose browning-whitening transdifferentiation and iron influx, which sheds light on the compromised adipose plasticity in conditions of dysregulated FoxO1 and Tgfβ1 signaling.

Distinct regulation of iron homeostasis in rat heart and liver in response to systemic iron deficiency

Chronic heart failure (HF) is characterized by severe cardiac mitochondrial dysfunction. Cellular energetic function is importantly regulated by iron since mitochondrial enzymes involved in oxidative phosphorylation, antioxidative defense and oxygen transport require iron-containing cofactors (heme, Fe-S clusters). In HF, systemic iron deficiency (ID) shows high prevalence (30–50%) and is associated with worse exercise capacity and increased mortality. Human and animal studies showed discordant results concerning iron content in failing heart, even reporting mitochondrial iron overload in some instance. This leads to a controversy of using iron chelation or iron supplementation as metabolic therapy for HF. Our aim was to investigate the regulation of key actors of cellular iron metabolism in the left (LV) and the right (RV) ventricles of two rat models of systemic ID. A comparative study was also performed in the liver, the main iron storage organ known to sense systemic ID. We developed two rat models of systemic ID without anaemia and cardiac remodelling, using low iron diet for 60 days, combined either with two distinct blood withdrawals at day 0 and 30 or with iron chelator deferiprone from day 1 to 60. Control rats were fed on a normal iron diet. Rats were sacrificed at day 60, serum and tissue iron contents were determined using a photometric colorimetric method. mRNA and protein levels of transferrin receptor 1 (TfR1), L-ferritin (L-Ft) and ferroportin (Fpn), involved in iron uptake, storage and export respectively were measured in biopsies of RV, LV and liver. Liver hepcidin, regulating systemic iron homeostasis, was analysed at mRNA level as well as cardiac hepcidin required for autonomous cellular iron homeostasis. Our main results showed that LV and RV maintained their iron content in a physiological range while the liver drastically decreased its iron pool in response to ID. In this condition, the RV exhibited a post-transcriptional regulation of both TfR1, L-Ft and Fpn similarly to the one found in the liver. In contrast, the LV showed a post-translational regulation of TfR1, a potential post-transcriptional regulation of L-Ft and no regulation for Fpn in ID. Our study showed that both ventricles initiate an adaptative response to maintain their physiological iron pool under systemic ID. These results should be confirmed in a HF model with systemic ID to better establish the benefits of iron chelation or supplementation in HF patients.