Total Elemental Iron Research Articles

Iron overload and impaired iron handling contribute to the dystrophic pathology in models of Duchenne muscular dystrophy.

BackgroundOxidative stress is implicated in the pathophysiology of Duchenne muscular dystrophy (DMD, caused by mutations in the dystrophin gene), which is the most common and severe of the muscular dystrophies. To our knowledge, the distribution of iron, an important modulator of oxidative stress, has not been assessed in DMD. We tested the hypotheses that iron accumulation occurs in mouse models of DMD and that modulation of iron through the diet or chelation could modify disease severity.MethodsWe assessed iron distribution and total elemental iron using LA‐ICP‐MS on skeletal muscle cross‐sections of 8‐week‐old Bl10 control mice and dystrophic mdx mice (with moderate dystrophy) and dystrophin/utrophin‐null mice (dko, with severe dystrophy). In addition, mdx mice (4 weeks) were treated with either an iron chelator (deferiprone 150 mg/kg/day) or iron‐enriched feed (containing 1% added iron as carbonyl iron). Immunoblotting was used to determine the abundance of iron‐ and mitochondria‐related proteins. (Immuno)histochemical and mRNA assessments of fibrosis and inflammation were also performed.ResultsWe observed a significant increase in total elemental iron in hindlimb muscles of dko mice (+50%, P < 0.05) and in the diaphragm of mdx mice (+80%, P < 0.05), with both tissues exhibiting severe pathology. Iron dyshomeostasis was further evidenced by an increase in the storage protein ferritin (dko: +39%, P < 0.05) and ferroportin compared with Bl10 control mice (mdx: +152% and dko: +175%, P < 0.05). Despite having features of iron overload, dystrophic muscles had lower protein expression of ALAS‐1, the rate‐limiting enzyme for haem synthesis (dko −44%, P < 0.05), and the haem‐containing protein myoglobin (dko −54%, P < 0.05). Deferiprone treatment tended to decrease muscle iron levels in mdx mice (−30%, P < 0.1), which was associated with lower oxidative stress and fibrosis, but suppressed haem‐containing proteins and mitochondrial content. Increasing iron via dietary intervention elevated total muscle iron (+25%, P < 0.05) but did not aggravate the pathology.ConclusionsMuscles from dystrophic mice have increased iron levels and dysregulated iron‐related proteins that are associated with dystrophic pathology. Muscle iron levels were manipulated by iron chelation and iron enriched feed. Iron chelation reduced fibrosis and reactive oxygen species (ROS) but also suppressed haem‐containing proteins and mitochondrial activity. Conversely, iron supplementation increased ferritin and haem‐containing proteins but did not alter ROS, fibrosis, or mitochondrial activity. Further studies are required to investigate the contribution of impaired ferritin breakdown in the dysregulation of iron homeostasis in DMD.

Extracts of Portulaca oleracea promote wound healing by enhancing angiology regeneration and inhibiting iron accumulation in mice

ObjectiveTo investigate the role of Portulaca oleracea (POL) in promoting revascularization and re-epithelization as well as inhibiting iron aggregation and inflammation of deep tissue pressure injury (DTPI). MethodsThe hydroalcoholic extract of POL (P) and aqueous phase fraction of POL (PD) were prepared based on maceration and liquid–liquid extraction. The number of new blood vessels and VEGF-A expression level were assessed using H&E stain and Western blot on injured muscle to examine the role of POL different extracts in vascularization. The iron distribution and total elemental iron of injured muscle were detected using laser ablation inductively coupled plasma mass spectrometry (ICP-MS) and Perls’ staining to determine whether POL extracts can inhibit the iron accumulation. Besides, the ability of POL extracts to promote wound healing by combining re-epithelization time, inflammation degree and collagen deposition area were comprehensively evaluated. ResultsIn vitro, we observed a significant increase in HUVEC cell viability, migration rate and the number of the tube after P and PD treatment (P < 0.05). In vivo, administration of P and PD impacted vascularization and iron accumulation on injured tissue, evident from more new blood vessels, higher expression of VEGF-A and decreased muscle iron concentration of treatment groups compared with no-treatment groups (P < 0.05). Besides, shorter re-epithelization time, reduced inflammatory infiltration and distinct collagen deposition were associated with administration of P and PD (P < 0.05). ConclusionPOL extract administration groups have high-quality wound healing, which is associated with increased new blood vessels, collagen deposition and re-epithelization, along with decreased iron accumulation and inflammatory infiltration. Our results suggest that that POL extract is beneficial to repair injured muscle after ischemia–reperfusion, highlighting the potential of POL in the DTPI treatment.

Efficacy of Iron Therapy on Fatigue and Work Capacity in Non-Anemic Iron Deficient Adults: A Systematic Review of Randomized Controlled Trials

INTRODUCTION: Iron supplementation in iron deficiency anemia is standard practice, but the benefits of iron supplementation in iron deficient non-anemic (IDNA) individuals remains controversial. We conducted a systematic review and meta-analysis to identify the effects of iron therapy on fatigue and work capacity in iron deficient non-anemic adults.METHODS: We included randomized controlled trials of adults (≥18 years) who were iron deficient but non-anemic. Interventions included oral, intramuscular or intravenous iron supplementation; all therapy doses, frequencies and durations were included. We included trials that evaluated outcomes at least 1 month from the initiation of iron therapy. Comparators included placebo or active therapy. Our primary outcome measures were self-reported fatigue and objective measures of work capacity. Secondary outcomes included the incidence of anemia, change in hemoglobin concentration and serum ferritin, and the incidence of adverse outcomes including iron toxicity, constipation, diarrhea, gastrointestinal intolerance and nausea. We searched Medline, Embase, CENTRAL, CINAHL, SportDiscus, and CAB Abstracts from inception to October 31, 2016. We searched the World Health Organization's ICTRP for relevant ongoing trials and performed forward searches of included trials and relevant reviews in Web of Science. We assessed internal validity of included trials using the Cochrane Risk of Bias tool, and the external validity using the GRADE methodology.RESULTS: From 11580 citations we included 18 unique trials, and 2 companion papers enrolling 1162 patients (Table 1). Trials were published between 1989 and 2015, and all trials were published in peer-reviewed journals. Exclusively healthy females (aged 17 to 55 years old) with varying levels of fitness (sedentary to well-trained) were enrolled in all but three studies. Iron interventions consisted of iron supplementation administered orally, intramuscularly or intravenously. Of the trials evaluating oral supplements, all but one used ferrous sulfate (13 trials, 721 participants). Intravenous iron was administered in three trials (395 participants), and intramuscular iron in one trial (16 participants). In trials using oral iron, the mean daily elemental iron dose was 86.9mg (± 49.1mg; range: 16 to 200mg). In trials reporting intravenous iron, the mean daily elemental iron dose was 566mg (± 330mg; range 200 to 1000mg) and mean total elemental iron dose 767mg (± 206mg; range 500 to 1000mg). Among all studies, the mean duration of iron therapy was 46 days (± 30 days; range 1 to 112 days), and mean duration of follow-up was 57 days (± 24 days; range 28 to 112 days). Fatigue was evaluated in four trials enrolling 714 participants. Iron supplementation was associated with a reduction in subjective measures of fatigue when assessed by either the Piper Fatigue Scale (PFS), the Current and Past Psychological State scale (CAPPS), visual analog scale or Brief Fatigue Inventory questionnaire (BFI) (SMD -0.38; 95% CI -0.52 to -0.23; I2 0%). Work capacity was reported in 10 trials (291 participants); all but one of the trials employed at least one of three common aerobic tests of work capacity: time trial, time to exhaustion, or VO2 max performance from a graded exercise test. In two trials (79 participants) that used 15 km time trials, iron supplementation was not associated with improved exercise capacity (SMD -0.09; 95% CI -0.53 to 0.35; I2 0%). In four trials (69 participants) that used time-to-exhaustion tests, iron supplementation did not significantly improve exercise capacity (SMD 0.25; 95% CI -0.22 to 0.73; I2 0%). Nine trials (235 participants) reported VO2 max as a surrogate measure of work capacity. Iron supplementation did not increase VO2 max (SMD 0.11; 95% CI -0.15 to 0.37; I2 0%).CONCLUSION: In iron deficient non-anemic adults, iron supplementation is associated with reduced subjective measures of fatigue, but not with objective improvements in work capacity. Given the global prevalence of both iron deficiency and fatigue, patients and practitioners could consider a course of iron supplementation to improve symptoms of fatigue in presence or absence of documented anemia. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Iron accumulation in skeletal muscles of old mice is associated with impaired regeneration after ischaemia-reperfusion damage.

BackgroundOxidative stress is implicated in the insidious loss of muscle mass and strength that occurs with age. However, few studies have investigated the role of iron, which is elevated during ageing, in age‐related muscle wasting and blunted repair after injury. We hypothesized that iron accumulation leads to membrane lipid peroxidation, muscle wasting, increased susceptibility to injury, and impaired muscle regeneration.MethodsTo examine the role of iron in age‐related muscle atrophy, we compared the skeletal muscles of 3‐month‐old with 22‐ to 24‐month‐old 129SvEv FVBM mice. We assessed iron distribution and total elemental iron using laser ablation inductively coupled plasma mass spectrometry and Perls' stain on skeletal muscle cross‐sections. In addition, old mice underwent ischaemia–reperfusion (IR) injury (90 min ischaemia), and muscle regeneration was assessed 14 days after injury. Immunoblotting was used to determine lipid peroxidation (4HNE) and iron‐related proteins. To determine whether muscle iron content can be altered, old mice were treated with deferiprone (DFP) in the drinking water, and we assessed its effects on muscle regeneration after injury.ResultsWe observed a significant increase in total elemental iron (+43%, P < 0.05) and lipid peroxidation (4HNE: +76%, P < 0.05) in tibialis anterior muscles of old mice. Iron was further increased after injury (adult: +81%, old: +135%, P < 0.05) and associated with increased lipid peroxidation (+41%, P < 0.05). Administration of DFP did not impact iron or measures of lipid peroxidation in skeletal muscle or modulate muscle mass. Increased muscle iron concentration and lipid peroxidation were associated with less efficient regeneration, evident from the smaller fibres in cross‐sections of tibialis anterior muscles (−24%, P < 0.05) and an increased percentage of fibres with centralized nuclei (+4124%, P < 0.05) in muscles of old compared with adult mice. Administration of DFP lowered iron after IR injury (PRE: −32%, P < 0.05 and POST: −41%, P < 0.05), but did not translate to structural improvements.ConclusionsMuscles from old mice have increased iron levels, which are associated with increased lipid peroxidation, increased susceptibility to IR injury, and impaired muscle regeneration. Our results suggest that iron is involved in effective muscle regeneration, highlighting the importance of iron homeostasis in muscle atrophy and muscle repair.

Comparison of the effects of oral iron treatment every day and every other day in female patients with iron deficiency anaemia.

It is known that daily divided doses and high doses of iron increase hepcidin and reduce iron absorption. This study aimed to compare treatments of iron replacement every other day at low doses, once a day and twice a day in terms of their effectiveness and frequencies of side effects. For a month, Group I received 270 mg ferrous sulphate twice a day (total elemental iron dose: 160 mg/day), Group II received 270 mg ferrous sulphate once a day (total elemental iron dose: 80 mg/day), and Group III received 270 mg ferrous sulphate every other day (total elemental iron dose: 80 mg/every other day). Intragroup and intergroup statistical analyses were carried out. Haemoglobin (Hb) increased significantly in all three groups (P = 0.00). The increase in Hb levels was similar among the groups (P = 0.09). Ferritin significantly increased in all three groups after the treatment (P = 0.00). The increase in ferritin in Group I was significantly higher than those in Groups II and III (P < 0.05). Gastrointestinal tract (GIS) side effects were also significantly higher in Group I in comparison to the others (P = 0.001). A low-dosage of iron treatment every other day may be used in the place of providing iron once or twice every day with similar effectiveness and lower rates of GIS side effects.

Complex refractive indices and single-scattering albedo of global dust aerosols in the shortwave spectrum and relationship to size and iron content

Abstract. The optical properties of airborne mineral dust depend on its mineralogy, size distribution, and shape, and they might vary between different source regions. To date, large differences in refractive index values found in the literature have not been fully explained. In this paper we present a new dataset of complex refractive indices (m=n-ik) and single-scattering albedos (SSAs) for 19 mineral dust aerosols over the 370–950 nm range in dry conditions. Dust aerosols were generated from natural parent soils from eight source regions (northern Africa, Sahel, Middle East, eastern Asia, North and South America, southern Africa, and Australia). They were selected to represent the global-scale variability of the dust mineralogy. Dust was resuspended into a 4.2 m3 smog chamber where its spectral shortwave scattering (βsca) and absorption (βabs) coefficients, number size distribution, and bulk composition were measured. The complex refractive index was estimated by Mie calculations combining optical and size data, while the spectral SSA was directly retrieved from βsca and βabs measurements. Dust is assumed to be spherical in the whole data treatment, which introduces a potential source of uncertainty. Our results show that the imaginary part of the refractive index (k) and the SSA vary widely from sample to sample, with values for k in the range 0.0011 to 0.0088 at 370 nm, 0.0006 to 0.0048 at 520 nm, and 0.0003 to 0.0021 at 950 nm, as well as values for SSA in the range 0.70 to 0.96 at 370 nm, 0.85 to 0.98 at 520 nm, and 0.95 to 0.99 at 950 nm. In contrast, the real part of the refractive index (n) is mostly source (and wavelength) independent, with an average value between 1.48 and 1.55. The sample-to-sample variability in our dataset of k and SSA is mostly related to differences in the dust iron content. In particular, a wavelength-dependent linear relationship is found between the magnitude of k and SSA and the mass concentrations of both iron oxide and total elemental iron, with iron oxide better correlated than total elemental iron with both k and SSA. The value of k was found to be independent of size. When the iron oxide content exceeds 3 %, the SSA linearly decreases with an increasing fraction of coarse particles at short wavelengths (&lt; 600 nm). Compared to the literature, our values for the real part of the refractive index and SSA are in line with past results, while we found lower values of k compared to most of the literature values currently used in climate models. We recommend that source-dependent values of the SW spectral refractive index and SSA be used in models and remote sensing retrievals instead of generic values. In particular, the close relationships found between k or SSA and the iron content in dust enable the establishment of predictive rules for spectrally resolved SW absorption based on particle composition.

Forms of iron in soils on basement complex rocks of Kaduna state in northern guinea Savanna of Nigeria

The forms of iron extracted by different methods were studied in soils developed on four basement complex rocks within Northern Guinea Savanna of Nigeria namely: migmatite gneisses, older granite, quartzites and mica schists. The study shows that forms of iron generally decreased in the order of total elemental iron (FeT) determined by XRF &gt; double acid extractable total iron (Fea) &gt; dithionite extractable iron oxide (Fed) &gt; oxalate extractable iron oxide (Fex) &gt; pyrophosphate extractable iron oxide (Fep) &gt; 0.1M HCl extractable micronutrient available iron (Feh). Variation in content of total irons (FeT and Fea) were not significant in the soils, but content of Feh, Fed, Fex and Fex/d significantly varied in the soils on the various parent materials. Therefore processes and extent of pedogenesis were considered to influence the variations resulting in recrystallization and increase in content of Feh and Fed in these soils. The significant correlation between various forms of Fe (Fea, Fed, and Fex) with active iron ratio further affirmed that as soils on basement complexes increase in their pedogenetic age, Fe content generally increases irrespective of total forms of iron. The strong correlation between FeT, Fea and Fed indicate that these forms of iron were extracted from similar sources.Keywords: Iron, basement complex rock, pedogenesis, Northern Guinea Savanna, Nigeria.

Dominance of goethite over hematite in iron oxides of mineral dust from Western Africa: Quantitative partitioning by X‐ray absorption spectroscopy

AbstractThis paper reports on the X‐ray absorption analysis of samples of mineral dust emitted from or transported to Western Africa. We found that iron oxides account, by mass, for 38% to 72% of the total elemental iron. They are composed of minerals in the Fe(III) oxidation state: goethite (FeO·OH) and hematite (Fe2O3). The apparent fraction of iron oxide attributed to goethite is higher than hematite regardless of the source region from which the dust originated. The goethite percent content of iron oxides is in the range 52–78% (by mass), the highest values being measured for dust originating in the Sahel. The limited number of samples analyzed and the sample‐to‐sample variability prevent us from concluding firmly on the regional variability of the goethite‐to‐hematite ratio. Based on the experimental data on mineralogical composition and on concurrent measurements of the number size distribution, the optical properties of mineral dust have been calculated in a Mie approximation for homogeneous spherical particles. At 550 nm, the single‐scattering albedo ω0 ranges between 0.89 and 0.93, the asymmetry factor g ranges between 0.76 and 0.8 and the mass extinction efficiency kext varies between 0.5 and 1.1 m2 g−1; these values are all in the range of those from independent direct measurements. Neglecting the partitioning between hematite and goethite and the assimilation of iron oxides by hematite, as it is often done with models, lowers the single‐scattering albedo and increases the asymmetry factor in the UV‐visible spectral region below 550 nm. The mass extinction efficiency is insensitive to the nature of the iron oxides but rather responds to variations in the number size distribution. The mineralogy of iron oxides should therefore be taken into account when assessing the effect of mineral dust on climate and atmospheric chemistry, in particular via interactions involving photolysis.

Iron supplementation in adolescent hemodialysis patients

Iron supplementation is necessary in children on hemodialysis, but the optimal protocol remains unknown. We studied the effects of changing our unit's protocol from oral iron with periodic doses of parenteral iron dextran to routine administration of parenteral sodium ferric gluconate on anemia and iron parameters. We followed seven hemodialysis patients aged 15 20 years (mean 17 years). Hemoglobin, hematocrit, serum iron, transferrin saturation, ferritin, erythropoietin dose, total elemental iron dose and total iron cost for the six months prior to the protocol change were compared to the same variables during the six months following the change. There was no statistically significant difference between the doses of parenteral iron between the two protocols; however, the total dose of elemental iron administered in the oral iron plus iron dextran protocol was greater than in the sodium ferric gluconate protocol (19.6+/-13.1 (mean+/-SD) mg/kg/week versus 1.1+/-0.3 mg/kg/week; p = 0.03). Both protocols had equivalent efficacy with respect to hemoglobin, ferritin and other measures of iron stores. On the other hand, the costs of sodium ferric gluconate were significantly higher than those of oral iron plus intermittent iron dextran (157.75+/-45.94 $/patient/month versus 52.08+/-49.88 $/patient/month; p = 0.01). Routine administration of sodium ferric gluconate is equivalent if not superior to use of oral iron plus iron dextran for maintenance of iron stores in adolescents on hemodialysis, but more expensive.

Accidental Childhood Iron Poisoning: A Problem of Marketing and Labeling

Accidental iron poisoning still represents a significant hazard in children less than 5 years of age. The problem is compounded by the attractiveness of dosage forms, their high availability, and ambiguities in product labeling. Manufacturers accentuate label ambiguity by not specifically designating the iron as being total elemental iron or iron compound. A list of products that contain iron has been prepared to help clarify this issue.