Development of an iron overload HepG2 cell model using ferrous ammonium citrate
Ontology highlight
ABSTRACT:
SUBMITTER: Abbasi U
PROVIDER: S-EPMC10713717 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:We examined nitrate-dependent Fe(2+) oxidation mediated by anaerobic ammonium oxidation (anammox) bacteria. Enrichment cultures of "Candidatus Brocadia sinica" anaerobically oxidized Fe(2+) and reduced NO3(-) to nitrogen gas at rates of 3.7 ± 0.2 and 1.3 ± 0.1 (mean ± standard deviation [SD]) nmol mg protein(-1) min(-1), respectively (37°C and pH 7.3). This nitrate reduction rate is an order of magnitude lower than the anammox activity of "Ca. Brocadia sinica" (10 to 75 nmol NH4(+) mg protein(-1) min(-1)). A (15)N tracer experiment demonstrated that coupling of nitrate-dependent Fe(2+) oxidation and the anammox reaction was responsible for producing nitrogen gas from NO3(-) by "Ca. Brocadia sinica." The activities of nitrate-dependent Fe(2+) oxidation were dependent on temperature and pH, and the highest activities were seen at temperatures of 30 to 45°C and pHs ranging from 5.9 to 9.8. The mean half-saturation constant for NO3(-) ± SD of "Ca. Brocadia sinica" was determined to be 51 ± 21 μM. Nitrate-dependent Fe(2+) oxidation was further demonstrated by another anammox bacterium, "Candidatus Scalindua sp.," whose rates of Fe(2+) oxidation and NO3(-) reduction were 4.7 ± 0.59 and 1.45 ± 0.05 nmol mg protein(-1) min(-1), respectively (20°C and pH 7.3). Co-occurrence of nitrate-dependent Fe(2+) oxidation and the anammox reaction decreased the molar ratios of consumed NO2(-) to consumed NH4(+) (ΔNO2(-)/ΔNH4(+)) and produced NO3(-) to consumed NH4(+) (ΔNO3(-)/ΔNH4(+)). These reactions are preferable to the application of anammox processes for wastewater treatment.
| S-EPMC3697569 | biostudies-literature
Project description:The transcriptome approach was used to characterize of the global change (2 time points) in Synechocystis gene expression in response to continuous exposure to iron excess (17 mM), compared to standard medium (17 microM). For each time point, total RNA were isolated from stressed and unstressed cells, reverse-transcribed, differentially labelled (dye swapped), hybridized together (stressed versus unstressed samples) and analyzed with DNA glass microarrays (two slides per each time point) (Custom-commercial array : IntelliGeneTM CyanoCHIP version 2.0, TAKARA). To identify differentially expressed genes, the median of the normalized ratio of Cy5/Cy3 intensity was calculated for each spot of the replicated dye-swap. The results of the analysis were carefully examined to exclude the dye effect between the 2 Cy-swapped arrays. Keywords: stress responses
2005-12-07 | GSE3715 | GEO
Project description:Ferrous ammonium phosphate (FAP) is an iron salt that has been developed for the fortification of food matrices sensitive to color and flavor changes. The objective of the study was to measure iron absorption from FAP in young children and compare it to a previous evaluation of FAP in young women. A double-blind randomized crossover study with two parallel arms was used to evaluate the iron absorption from FAP added to reconstituted milk powder in comparison to that from ferrous sulfate (FeSO4) and ferric pyrophosphate (FePP). Iron absorption was measured in 39 children aged 3- to 6-years-old using erythrocyte incorporation of stable Fe isotopes (57Fe, 58Fe). The geometric mean iron absorption in iron replete children from FAP, FeSO4 and FePP from milk was 8.3%, 7.6% and 2.1%, respectively. Iron absorption from FAP and FeSO4 fortified milk was not significantly different (p = 0.199); however, it was significantly higher than from FePP fortified milk (p < 0.001). Iron bioavailability from FAP and FePP relative to FeSO4 (relative bioavailability (RBV)) was 110% and 33%, respectively. The RBV of FAP (110%) in iron replete children was higher than previously reported RBV (71%) in mainly iron deficient women. The difference in iron status between the children and women in the respective studies may explain the different RBV values and is discussed.
| S-EPMC9031871 | biostudies-literature
Project description:Background and objectivesFerric citrate is an oral medication approved for treatment of iron deficiency anemia in patients with CKD not requiring dialysis. The relative efficacy of ferric citrate versus ferrous sulfate in treating iron deficiency in patients with CKD is unclear.Design, setting, participants, & measurementsWe randomized 60 adults with moderate to severe CKD (eGFR 15-45 ml/min per 1.73 m2) and iron deficiency (transferrin saturation [TSAT] ≤30% and ferritin ≤300 ng/ml) to ferric citrate (2 g three times a day with meals, n=30) or ferrous sulfate (325 mg three times a day, n=30) for 12 weeks. Primary outcomes were change in TSAT and ferritin from baseline to 12 weeks. Secondary outcomes were change in hemoglobin, fibroblast growth factor 23 (FGF23), and hepcidin.ResultsBaseline characteristics were well balanced between study arms. There was a greater increase in TSAT (between-group difference in mean change, 8%; 95% confidence interval [95% CI], 1 to 15; P=0.02) and ferritin (between-group difference in mean change, 37 ng/ml; 95% CI, 10 to 64; P=0.009) from baseline to 12 weeks in participants randomized to ferric citrate as compared with ferrous sulfate. Similarly, as compared with ferrous sulfate, treatment with ferric citrate resulted in a greater increase in hepcidin from baseline to 12 weeks (between-group difference, 69 pg/ml; 95% CI, 8 to 130). There were no between-group differences in mean change for hemoglobin (0.3 g/dl; 95% CI, -0.2 to 0.8), intact FGF23 (-29 pg/ml; 95% CI, -59 to 0.1), or C-terminal FGF23 (61 RU/ml; 95% CI, -181 to 58). The incidence of adverse events did not differ between treatment arms.ConclusionsAs compared with ferrous sulfate, treatment with ferric citrate for 12 weeks resulted in a greater mean increase in TSAT and ferritin concentrations in individuals with moderate to severe CKD and iron deficiency.Clinical trial registry name and registration numberImpact of Ferric Citrate vs Ferrous Sulfate on Iron Parameters and Hemoglobin in Individuals With Moderate to Severe Chronic Kidney Disease (CKD) With Iron Deficiency, NCT02888171.
| S-EPMC7480557 | biostudies-literature
Project description:BackgroundIron deficiency in children can have significant neurological consequences, and iron supplementation is an effective treatment of choice. However, traditional routes of iron supplementation do not allow efficient iron delivery to the brain due to the presence of the blood-brain barrier. So an easily delivered iron formulation with high absorption efficiency potentially could find widespread application in iron deficient infants.ResultsIn this study, we have developed and characterized a nanovesicular formulation of ferric ammonium citrate (ferric ammonium citrate nanoliposomes, FAC-LIP) and have shown that it can increase brain iron levels in rats following nasal administration. FAC was incorporated into liposomes with high efficiency (97%) and the liposomes were small (40 nm) and stable. Following intranasal delivery in rats, FAC-LIP significantly increased the iron content in the olfactory bulb, cerebral cortex, striatum, cerebellum and hippocampus, and was more efficient at doing so than FAC alone. No signs of apoptosis or abnormal cell morphology were observed in the brain following FAC-LIP administration, and there were no significant changes in the levels of SOD and MDA, except in the cerebellum and hippocampus. No obvious morphological changes were observed in lung epithelial cells or tracheal mucosa after nasal delivery, suggesting that the formulation was not overtly toxic.ConclusionsIn this study, nanoscale FAC-LIP proved an effective system delivering iron to the brain, with high encapsulation efficiency and low toxicity in rats. Our studies provide the foundation for more detailed investigations into the applications of niosomal nasal delivery of liposomal formulations of iron as a simple and safe therapy for iron deficiency anemia. Graphical abstract The diagrammatic sketch of "Nasal delivery of nanoliposome-encapsulated ferric ammonium citrate can increase the iron content of rat brain". Nanoliposome-encapsulated ferric ammonium citrate (FAC-LIP) was successfully prepared and intranasal administration of FAC-LIP increased both the total iron contents and iron storage protein (FTL) expression in rat olfactory bulb, cerebral cortex, striatum and hippocampus, compared with those of FAC groups. Moreover, there was not overtly toxic affects to brain, lung epithelial cells and tracheal mucosa.
| S-EPMC5457662 | biostudies-literature
Project description:BACKGROUND:The iron-based phosphate binders, sucroferric oxyhydroxide (SFOH) and ferric citrate (FC), effectively lower serum phosphorus in clinical studies, but gastrointestinal iron absorption from these agents appears to differ. We compared iron uptake and tissue accumulation during treatment with SFOH or FC using experimental rat models. METHODS:Iron uptake was evaluated during an 8-h period following oral administration of SFOH, FC, ferrous sulphate (oral iron supplement) or control (methylcellulose vehicle) in rat models of anaemia, iron overload and inflammation. A 13-week study evaluated the effects of SFOH and FC on iron accumulation in different organs. RESULTS:In the pharmacokinetic experiments, there was a minimal increase in serum iron with SFOH versus control during the 8-h post-treatment period in the iron overload and inflammation rat models, whereas a moderate increase was observed in the anaemia model. Significantly greater increases (P < 0.05) in serum iron were observed with FC versus SFOH in the rat models of anaemia and inflammation. In the 13-week iron accumulation study, total liver iron content was significantly higher in rats receiving FC versus SFOH (P < 0.01), whereas liver iron content did not differ between rats in the SFOH and control groups. CONCLUSIONS:Iron uptake was higher from FC versus SFOH following a single dose in anaemia, iron overload and inflammation rat models and 13 weeks of treatment in normal rats. These observations likely relate to different physicochemical properties of SFOH and FC and suggest distinct mechanisms of iron absorption from these two phosphate binders.
| S-EPMC7282824 | biostudies-literature
Project description:Iron is an essential nutrient for cell survival and is crucial for DNA replication, mitochondrial function and erythropoiesis. However, the immunological role of iron in viral infections has not been well defined. Here we found the iron salt ferric ammonium citrate (FAC) inhibited Influenza A virus, HIV virus, Zika virus, and Enterovirus 71 (EV71) infections. Of note, both iron ion and citrate ion were required for the antiviral capability of FAC, as other iron salts and citrates did not exhibit viral inhibition. Mechanistically, FAC inhibited viral infection through inducing viral fusion and blocking endosomal viral release. These were further evidenced by the fact that FAC induced liposome aggregation and intracellular vesicle fusion, which was associated with a unique iron-dependent cell death. Our results demonstrate a novel antiviral function of FAC and suggest a therapeutic potential for iron in the control of viral infections.
| S-EPMC5871618 | biostudies-literature
Project description:The opportunistic pathogen Pseudomonas aeruginosa forms biofilms, which render it more resistant to antimicrobial agents. Levels of iron in excess of what is required for planktonic growth have been shown to promote biofilm formation, and therapies that interfere with ferric iron [Fe(III)] uptake combined with antibiotics may help treat P. aeruginosa infections. However, use of these therapies presumes that iron is in the Fe(III) state in the context of infection. Here we report the ability of phenazine-1-carboxylic acid (PCA), a common phenazine made by all phenazine-producing pseudomonads, to help P. aeruginosa alleviate Fe(III) limitation by reducing Fe(III) to ferrous iron [Fe(II)]. In the presence of PCA, a P. aeruginosa mutant lacking the ability to produce the siderophores pyoverdine and pyochelin can still develop into a biofilm. As has been previously reported (P. K. Singh, M. R. Parsek, E. P. Greenberg, and M. J. Welsh, Nature 417:552-555, 2002), biofilm formation by the wild type is blocked by subinhibitory concentrations of the Fe(III)-binding innate-immunity protein conalbumin, but here we show that this blockage can be rescued by PCA. FeoB, an Fe(II) uptake protein, is required for PCA to enable this rescue. Unlike PCA, the phenazine pyocyanin (PYO) can facilitate biofilm formation via an iron-independent pathway. While siderophore-mediated Fe(III) uptake is undoubtedly important at early stages of infection, these results suggest that at later stages of infection, PCA present in infected tissues may shift the redox equilibrium between Fe(III) and Fe(II), thereby making iron more bioavailable.
| S-EPMC3133341 | biostudies-literature
Project description:BackgroundR2*-MRI is clinically used to noninvasively assess hepatic iron content (HIC) to guide potential iron chelation therapy. However, coexisting pathologies, such as fibrosis and steatosis, affect R2* measurements and may thus confound HIC estimations.PurposeTo evaluate whether a multispectral auto regressive moving average (ARMA) model can be used in conjunction with quantitative susceptibility mapping (QSM) to measure magnetic susceptibility as a confounder-free predictor of HIC.Study typePhantom study and in vivo cohort.SubjectsNine iron phantoms covering clinically relevant R2* range (20-1200/second) and 48 patients (22 male, 26 female, median age 18 years).Field strength/sequenceThree-dimensional (3D) and two-dimensional (2D) multi-echo gradient echo (GRE) at 1.5 T.AssessmentARMA-QSM modeling was performed on the complex 3D GRE signal to estimate R2*, fat fraction (FF), and susceptibility measurements. R2*-based dry clinical HIC values were calculated from the 2D GRE acquisition using a published R2*-HIC calibration curve as reference standard.Statistical testsLinear regression analysis was performed to compare ARMA R2* and susceptibility-based estimates to iron concentrations and dry clinical HIC values in phantoms and patients, respectively.ResultsIn phantoms, the ARMA R2* and susceptibility values strongly correlated with iron concentrations (R2 ≥ 0.9). In patients, the ARMA R2* values highly correlated (R2 = 0.97) with clinical HIC values with slope = 0.026, and the susceptibility values showed good correlation (R2 = 0.82) with clinical dry HIC values with slope = 3.3 and produced a dry-to-wet HIC ratio of 4.8.Data conclusionThis study shows the feasibility that ARMA-QSM can simultaneously estimate susceptibility-based wet HIC, R2*-based dry HIC and FFs from a single multi-echo GRE acquisition. Our results demonstrate that both, R2* and susceptibility-based wet HIC values estimated with ARMA-QSM showed good association with clinical dry HIC values with slopes similar to published R2*-biopsy HIC calibration and dry-to-wet tissue weight ratio, respectively. Hence, our study shows that ARMA-QSM can provide potentially confounder-free assessment of hepatic iron overload.Level of evidence3 TECHNICAL EFFICACY: Stage 2.
| S-EPMC9223690 | biostudies-literature
Project description:Oral iron preparations are used as first-line treatment for iron deficiency anemia (IDA), but their gastrointestinal side effects prevent patients from appropriate adherence. We recently conducted a randomized, double-blind, phase 3 non-inferiority study to evaluate the efficacy and safety of two dosages of ferric citrate hydrate (FC) compared with sodium ferrous citrate (SF) in patients with IDA. FC at both 500 and 1000 mg/day was non-inferior to SF at 100 mg/day in terms of the change in the hemoglobin concentration at Week 7 from baseline. Logistic regression analysis suggested that the cumulative proportion of patients who achieved the target hemoglobin concentration (≥ 13.0 g/dL in male patients and ≥ 12.0 g/dL in female patients) at Week 7 was highest among those treated with FC at 1000 mg/day, followed by SF at 100 mg/day and FC at 500 mg/day. Both dosages of FC were well tolerated in patients with IDA. The incidences of nausea and vomiting were significantly lower in the FC treatment groups than in the SF group. In conclusion, FC has potential to be an oral iron preparation with sufficient efficacy for the treatment of IDA and a lower risk of nausea and vomiting.
| S-EPMC10917848 | biostudies-literature