Iron Saccharate Research Articles

Efficacy and safety of a food supplement for iron deficiency anaemia: A monocentric prospective study

Iron deficiency anaemia (IDA) is the most prevalent worldwide nutrient deficiency-related disease. The 30% of IDA female patients is represented by non-pregnant women and the 42% are pregnant women. Oral iron supplementation represents the first-line treatment for IDA. Iron sulphate is the main source of iron, but despite its effectiveness, its use correlates with a high incidence of side effects. Consequently, finding new iron sources became challenging. An innovative microencapsulated and micronized iron saccharate, empowered with vitamins (B6, B12, B9 and C), has been evaluated for the efficacy and safety in a monocentric prospective observational study. 80 female subjects diagnosed for IDA received one dose/daily of the food supplement for an observation period of 60 days (T60) and 120 days (T120). To measure IDA-related biochemical parameters, full blood tests have been collected at each time. To evaluate Quality-of-Life (QoL) the Short-form 12 Physical Component Summary and Mental Component Summary (SF-12 PCS and MCS) together with sign and symptoms collection have been used to follow improvements in IDA-related indicators. Finally, side effects have been registered along the observation period. Obtained data revealed that the food supplement was effective and well tolerated. Changes in haemoglobin levels and other iron metabolism values have been observed, confirming the effectiveness of the tested product, from the biochemical point of view. In parallel, QoL improvement and signs and symptoms reduction confirm the high bioavailability and tolerability of this innovative iron source.

Possibilities of Correcting Iron Deficiency Anemia Caused by Chronic Kidney Disease Complicated by Chronic Heart Failure

Abstract: The study evaluated the effectiveness of intravenous administration of iron saccharate (Sufer® preparation) for 2 weeks in 12 patients with iron deficiency anemia due to chronic kidney disease, who were examined and treated in the nephrology department of the Dnepropetrovsk Regional Clinical Hospital named after I.I. Mechnikov. Inclusion of iron (III) hydroxide sucrose complex into therapy led to a significant increase in hemoglobin, ferritin, iron in blood plasma, and contributed to a decrease in creatinine levels (p<0.01). The increase in hemoglobin level began already from the 5th day of treatment. After 2 weeks, the hemoglobin level increased by 13% (p<0.01). When using the drug, there were no significant side effects that required a change in its daily dose or discontinuation of treatment. The therapeutic effect and good tolerance of iron (III) sucrose complex hydroxide allow us to recommend it as the drug of choice for iron deficiency anemia in patients with chronic kidney disease. Keywords: chronic kidney disease, iron deficiency anemia, iron saccharate, Sufer®.

Asbestos-induced mesothelial injury and carcinogenesis: Involvement of iron and reactive oxygen species.

Asbestos fibers have been used as an industrial and construction material worldwide due to their high durability and low production cost. Commercial usage of asbestos is currently prohibited in Japan; however, the risk of asbestos-induced malignant mesothelioma (MM) remains. According to epidemiological data, the onset of MM is estimated to occur after a latent period of 30-40 years from initial exposure to asbestos fibers; thus, the continuous increase in MM is a concern. To explore the molecular mechanisms of MM using animal models, iron saccharate with iron chelator-induced sarcomatoid mesothelioma (SM) revealed hallmarks of homozygous deletion of Cdkn2a/2b by aCGH and microRNA-199/214 by expression microarray. Oral treatment of iron chelation by deferasirox decreased the rate of high-grade SM. Moreover, phlebotomy delayed MM development in crocidolite-induced MM in rats. In Divalent metal transporter 1 (Dmt1) transgenic mice, MM development was delayed because of low reactive oxygen species (ROS) production. These results indicate the importance of iron and ROS in mesothelial carcinogenesis. The aims of this review focus on the pathogenesis of elongated mineral particles (EMPs), including asbestos fibers and multiwalled carbon nanotubes (MWCNTs) that share similar rod-like shapes in addition to the molecular mechanisms of MM development.

Evaluation of the Impact of Iron Deficiency Anemia during Pregnancy on Hospital Admission and Utilization of Hospital Resources in Latifa Women and Children Hospital, Dubai, UAE

Introduction: Iron deficiency anemia (IDA) is endemic among pregnant females worldwide. Liposomal iron preparation is a novel therapy for treating IDA in pregnant females. There is a lack of research on cost-effect and comparison between various new iron preparations as liposomal and intravenous (IV) iron supplements in the international literature. Objective: The objective of this study was to evaluate the cost-effect and maternal-fetal outcome of IDA during pregnancy in Latifa Women and Children Hospital, Dubai, UAE. Design: The study was a quasi-experimental study. Settings: Settings include tertiary-care hospital settings affiliated with academic center in UAE. Patients and Methods: A total of 226 pregnant women were inducted in the study who were controlled in terms of age, BMI, baseline hemoglobin (Hb), severity of anemia, and ferritin levels. There were 116 patients who received oral liposomal iron pyrophosphate and 110 patients received IV iron saccharate complex for 4 weeks. The overall cost-effect and maternal-fetal outcomes were compared in 2 groups. Main Outcomes Measured: The main outcomes measured the cost-effect of liposomal and IV iron therapy, and the 2 treatments were compared in terms of maternal and fetal outcomes. Result: The subjects were matched for age and body mass index and showed that the patients in the IV group were more symptomatic than those in the oral group (18.1 vs. 31.9% p value <0.01). There was no statistically significant difference among women from different nationalities living in UAE (p value 0.079). There were 98 (84.4%) patients in the oral group and 99 (90%) patients in the IV group who achieved the desired Hb levels after 1 month of treatment (p value = 0.878). Moreover, the side effects were also comparable in both groups (1.72 vs. 1.82% p value = 0.56). The incremental cost-effect ratio for IV iron was USD 108,633/rise to desired Hb. Conclusion: Liposomal iron preparations may be cost-effective and have fewer side effects than IV iron. In terms of outcome, the maternal and fetal variables are comparable in liposomal and IV groups.

Patient Blood Management in obstetrics

Background. Patient blood management (PBM) in obstetrics is the timely application of evidence-based therapeutic and surgical concepts, aimed at maintaining hemoglobin concentration, optimizing hemostasis, and minimizing blood loss to improve clinical outcomes for the patient.&#x0D; Objective. To describe PBM in obstetrics.&#x0D; Materials and methods. Analysis of literature data on this issue.&#x0D; Results and discussion. Risk factors for increased blood loss include the history peculiarities (cesarean section, postpartum hemorrhage, rapid delivery), placenta previa, placenta accreta, multiple pregnancy, polyhydramnios, large fetus, comorbid conditions of the mother. The prevalence of postpartum anemia in 48 hours after delivery is about 50 % in Europe and up to 80 % in developing countries. The reasons for insufficient detection and correction of anemia and iron deficiency in the antenatal period include the lack of standardized examinations for iron deficiency and algorithms for its treatment, incomplete history, and misinterpretation of examination results. Most obstetric guidelines recommend screening for anemia in pregnant women only with a comprehensive blood test without ferritin. Early identification of anemia allows to eliminate it before entering the labor process. Ways to solve the problem of anemia in pregnant women and women in labor include the detection of iron deficiency before pregnancy or in its early stages, correction of iron deficiency with oral (first trimester) or intravenous (third trimester) drugs. In case of the increased blood loss during childbirth or abdominal delivery, rapid correction of iron deficiency with iron saccharate may be required. The consensus of the Network for the Advancement of PBM, Hemostasis and Thrombosis Prevention (NATA) recommends that maximum efforts must be made to treat iron deficiency anemia before delivery. Severe cases may require hospital settings. To eliminate individually calculated postpartum iron deficiency, it is recommended to use intravenous drugs (Sufer, “Yuria-Pharm”). After cesarean section, the aministration of uterotonics (oxytocin) is recommended. In women at increased risk of postpartum hemorrhage, the administration of tranexamic acid (Sangera, “Yuria-Pharm”) should also be considered. The WOMAN project (The World Maternal Antifibrynolytic) aimed to determine the effect of early administration of tranexamic acid on mortality, hysterectomy and other adverse effects of bleeding. About 20,000 women who received tranexamic acid or placebo were examined. Significantly lower bleeding mortality was observed with tranexamic acid (1.5 % vs. 1.9 % in the placebo group; p&lt;0.045). It is recommended to enter the first dose of this drug as soon as possible (within the first 3 hours) from the beginning of bleeding, the second – in case of the effect absence of effect in 30 minutes.&#x0D; Conclusions. 1. PBM in obstetrics is the timely application of evidence-based therapeutic and surgical concepts aimed at maintaining hemoglobin concentration, optimizing hemostasis and minimizing blood loss. 2. Early identification of anemia allows to eliminate it before entering the labor process. 3. Ways to solve the problem of anemia in pregnant women and women in labor are the detection of iron deficiency before pregnancy or in its early stages, correction of iron deficiency with oral (first trimester) or intravenous (third trimester) drugs. 4. To eliminate postpartum iron deficiency, it is recommended to use intravenous drugs (Sufer). 5. In women at increased risk of postpartum hemorrhage, the administration of tranexamic acid (Sangerа) should also be considered.

The Prevalence of Lymphocytopenia Among Arab Population with Iron Deficiency Anemia an Experience from Qatar

Introduction Iron deficiency anaemia (IDA) is one of the most common health problems worldwide, its prevalence is up to 1 in 5 of the general population. The diagnosis of absolute iron deficiency is easy unless the condition is masked by inflammatory conditions. All cases of iron deficiency should be assessed for treatment and underlying cause.In developing countries, iron deficiency anemia is nutritional, resulting from reduced intake of bioavailable iron , and often associated with infections causing hemorrhages, such as hookworm infestation . In Western societies, other than in individuals at risk, iron depletion results from chronic bleeding and/or reduced iron absorption, disorders that may be more relevant than anemia itself.The association between IDA and lymphocytopenia is poorly addressed in the literature. Objective: To assess the prevalence of lymphocytopenia in a large cohort with IDA and to study the effect of iron replacement on lymphocytes count. Materials and Methods We retrospectively reviewed the electronic medical records of patients attended haematology clinic with the diagnosis of IDA over 2 years in Hamad Medical Corporation, Qatar. Patients with other forms of anemia were excluded as those with chronic or systemic diseases. Complete blood count and iron parameters were collected and analysed. Lymphocytopenia was defined as lymphocyte count less than 1000/microlitre. Statistical analysis was done using mean and SD and paired t test to compare variables after versus before treatment. Results The mean age of our IDA patients was 37.95 years with a mean BMI = 31.82. Out of 1567 case of IDA, 20 had lymphocytopenia, (1.276%). The mean lymphocytes count mean increased from 0.73 +/- 0.15 x 10^9 before iron replacement, to 1.79 +/- 0.74 x 10^9 after iron treatment (p &amp;lt; 0.05) (iron dose of 1000 mg of IV iron saccharate or ferric carboxymaltose) . Four out of the 20 patients with lymphopenia had mild infections (2 upper respiratory tract infections, 1 urinary tract infection and one gastroenteritis) with no serious complications. These findings suggested that the lymphopenia associated with IDA is correctable and does not increase infection risk in these patients. Discussion Our study showed a possible negative impact of IDA on lymphocytes count in a small number of patients that was corrected with the correction of anemia with iron therapy. Animal studies showed that iron deficiency may lead to impaired T lymphoid differentiation and may negatively affect all cell lineage in haematopoiesis not only on erythroid line. A case control study by Das et al. found significantly lower levels of CD4+ T-cell counts and CD4:CD8 ratios in iron deficient children, however there was no significant effect on immunoglobulin levels. Conclusions: Lymphopenia may occur in a small percentage of patients with IDA. Significant increase in the lymphocyte count occur with iron therapy and correction of the anemia. Lymphopenia was not associated with serious infections. Disclosures No relevant conflicts of interest to declare.

Overexpression of miR-199/214 is a distinctive feature of iron-induced and asbestos-induced sarcomatoid mesothelioma in rats.

Malignant mesothelioma (MM) is one of the most lethal tumors in humans. The onset of MM is linked to exposure to asbestos, which generates reactive oxygen species (ROS). ROS are believed to be derived from the frustrated phagocytosis and the iron in asbestos. To explore the pathogenesis of MM, peritoneal MM was induced in rats by the repeated intraperitoneal injection of iron saccharate and nitrilotriacetate. In the present study, we used microarray techniques to screen the microRNA (miR) expression profiles of these MM. We observed that the histological subtype impacted the hierarchical clustering of miR expression profiles and determined that miR‐199/214 is a distinctive feature of iron saccharate‐induced sarcomatoid mesothelioma (SM). Twist1, a transcriptional regulator of the epithelial‐mesenchymal transition, has been shown to activate miR‐199/214 transcription; thus, the expression level of Twist1 was examined in iron‐induced and asbestos‐induced mesotheliomas in rats. Twist1 was exclusively expressed in iron saccharate‐induced SM but not in the epithelioid subtype. The Twist1‐miR‐199/214 axis is activated in iron saccharate‐induced and asbestos‐induced SM. The expression levels of miR‐214 and Twist1 were correlated in an asbestos‐induced MM cell line, suggesting that the Twist1‐miR‐199/214 axis is preserved. MeT5A, an immortalized human mesothelial cell line, was used for the functional analysis of miR. The overexpression of miR‐199/214 promoted cellular proliferation, mobility and phosphorylation of Akt and ERK in MeT5A cells. These results indicate that miR‐199/214 may affect the aggressive biological behavior of SM.

A cohort study of two intravenous treatments for iron deficiency in patients with heart failure

Background: Iron deficiency (ID) in patients with heart failure (HF) leads to greater morbidity and mortality and its treatment has been associated with significant improvements in quality of life. Since no head-to-head studies are available, there is uncertainty as to which intravenous iron supplement should be used. This study aimed to compare the effect of ferric carboxymaltose (FCM) and iron saccharate (IS) on clinical and biochemical outcomes in patients with HF and ID.Methods: We reviewed electronic health records from a referral centre in Bogotá, Colombia for patients with HF. We selected records with a follow-up of at least 2 years. Primary outcomes were clinically significant changes in EuroQol-5D (EQ-5D) , 6-minute-walk test (6MWT), resolution of ID, and direct costs.Results: We obtained data on 119 patients with a median age of 69 years and a median left ventricular ejection fraction (LVEF) of 35%. All patients met criteria for ID, and 58% were treated with FCM. A significant difference in GFR of 11 mL/min/1.72 m2 was found at baseline between groups. Neither bivariate, nor multivariate analyses could identify significant differences between patients receiving FCM and IS for any of the primary outcomes. Direct cost analysis showed that FCM use generates 2.8 times the cost associated with saccharate use.Conclusions: This retrospective cohort study did not identify any significant differences in clinical or biochemical outcomes between HF patients with ID receiving FCM or IS. Direct cost analysis favoured use of IS in this group of patients.

Logistic regression analysis on correlative factors of phlebitis caused by iron sucrose injection

Objective To explore the correlative factors of phlebitis caused by iron sucrose injection through intravenous drip in Department of Orthopedics so as to provide a basis for take pertinently preventive steps. Methods A total of 588 inpatients with iron sucrose injection through intravenous drip in Department of Orthopedics of West China Hospital, Sichuan University were selected, by convenient sampling from December 2016 to May 2017. This research recorded the ages, sexes, whether they were with hypertension, body mess index (BMI) , vascular condition, retaining time and models of detaining needle, concentrations of iron saccharate, daily infusion quantity, days using iron saccharate, seniority of puncture nurses, whether there were with phlebitis through the correlative factors of phlebitis caused by iron sucrose injection through intravenous drip record sheet. Single factor and multiple factors Logistic stepwise regression was used to analyze the influencing factors of phlebitis. Results There were 69 cases (11.73%) with phlebitis in patients with ron sucrose injection treatment. Single factor analysis showed that there were statistically significant differences in the incidence of phlebitis among different sexes, daily infusion quantity, vascular condition, retaining time of detaining needle, type of detaining needle concentrations of iron saccharate of patients (χ2=8.654, 32.587, 68.313, 136.206, 10.662, 10.191; P<0.05) . Logistic regression analysis revealed that the independent risk factors of phlebitis caused by iron sucrose injection through intravenous drip included daily infusion quantity, retaining time of detaining needle, concentrations of iron saccharate, and the protective factors of that involved the vascular condition and the type of detaining needle. Conclusions Take pertinently preventive steps actively when patients in Department of Orthopedics are with iron sucrose injection through intravenous drip so as to lessen the suffering of the patients. Key words: Hospital, orthopedic; Phlebitis; Multivariate analysis; Injections, intravenous; Iron sucrose injection; Influencing factors

Elevated Neutrophil Gelatinase Lipocalin Levels Are Associated With Increased Oxidative Stress in Hemodialysis Patients.

BackgroundAdministration of intravenous iron is an essential treatment of anemia in hemodialysis patients, but it may lead to oxidative stress and increased morbidity and mortality. There is evidence that neutrophil gelatinase-associated lipocalin (NGAL) is protective against oxidative stress and thus the aim of the present study was to investigate the relationship between plasma NGAL and advanced oxidative protein products (AOPP) in hemodialysis patients treated with intravenous iron.MethodsIn a prospective study, 47 hemodialysis patients (mean age 63 years, SD = 13.6; 40% women) were enrolled from two separate hospitals. Oxidative stress was induced by an intravenous administration of 100 mg iron saccharate 0.5 h after the start of dialysis. Blood samples were drawn at the beginning of the dialysis, 0.5 h after iron administration and at the end of dialysis. NGAL levels were measured from the first blood sample, AOPP levels were measured from all blood samples.ResultsOur results showed that higher NGAL and AOPP levels at the beginning of the dialysis, prior to iron administration, significantly predicted higher levels of AOPP toward the end of dialysis, (β = 0.355, SE = 0.054, P = 0.035; β = 0.297, SE = 0.159, P = 0.043, respectively).ConclusionsOur results suggest that higher level of NGAL is a risk factor for oxidative stress, as measured by AOPP levels, in dialysis patients receiving intravenous iron. Our findings could identify dialysis patients who are at higher risk from iron supplementation via measurement of NGAL levels.

Heme iron polypeptide (proferrin®-ES) versus iron saccharate complex (ferrosac) for treatment of iron deficiency anemia during pregnancy

Objectives: Anemia is one of the world's leading causes of considerable perinatal morbidity and mortality. This study designed to compare the efficacy and safety of Heme iron polypeptide (Proferrin®-ES) versus iron saccharate complex (Ferrosac) in treatment of iron deficiency anemia during pregnancy. Methods: Two hundred and sixty (260) pregnant women with hemoglobin level below 10 gm/dl due to iron deficiency anemia were included in this study and randomized to receive either; intravenous Iron Saccharate (IV group) or oral Proferrin®-ES (PO group) for correction of iron deficiency anemia during pregnancy. Treatment efficacy checked by comparing pre-treatment values of hemoglobin, serum ferritin, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and reticulocytes count by the 3-months` post-treatment values. Results: The 3-months` post-treatment hemoglobin level increased compared to the pre-treatment level without any significant difference between the two studied groups (from 8.5 ± 3.5 to 11.3 ± 1.3 gm/dl in PO group and from 8.7 ± 2.5 to 11.7 ± 0.9 gm/dl in IV group). In addition; the 3-months` post-treatment ferritin level, increased compared to the pre-treatment level without any significant difference between the two studied groups (from 19.4 ± 4.9 to 118.8 ± 7.1 ug/l in PO group and from 15.3 ± 5.6 to 122.3 ± 6.4 ug/l in IV group). 1.6% (2/124) of the studied women developed gastrointestinal intolerance and upset with oral Proferrin®-ES (insignificant difference and excluded from the study) and no other side effects recorded with oral Proferrin®-ES. Conclusion: HIP (Proferrin®-ES) is an effective, safe, well tolerable oral iron preparation as well as intravenous iron saccharate complex for treatment of iron deficiency during pregnancy; it increases the hemoglobin and replaces the depleted iron store.

Effect of levocarnitine/iron saccharate combination on renal anaemia and oxidative stress in patients undergoing haemodialysis

Purpose: To investigate the effect of a combination of levocarnitine and iron saccharate on the treatment of renal anaemia and oxidative stress in patients undergoing haemodialysis. Methods: A total of 156 patients with renal anaemia were divided randomly into control (78 cases) and test groups (78 cases). Patients in the control group were treated with erythropoietin (EPO), iron saccharate, and conventional symptomatic treatment, while patients in the test group were treated with levocarnitine additionally. Anaemia indices, oxidative stress indices, response rate, and EPO dose were compared. Results: At week 28, the levels of hemoglobin b (Hb), hematocrit (Hct), serum ferritin (SF), and transferrin saturation (TSAT) in the test group were 92.72 ± 12.51 g/L, 34.74 ± 5.89 vol %, 245.61 ± 81.35 ng/mL, and 24.34 ± 5.32 %, respectively, which were much lower than the levels in the test group (114.36 ± 12.27 g/L, 40.23 ± 5.78 vol %, 345.07 ± 85.93 ng/mL, and 29.76 ± 5.41 %, respectively; p < 0.05). The levels of advanced oxidation protein products (AOPP) and malonaldehyde (MDA) in the test group were much higher than those of the control group (121.77 ± 31.65 nmol/L vs 89.65 ± 30.53 nmol/L; 9.58 ± 2.64 nmol/L vs 4.81 ± 2.57 nmol/L, respectively (p < 0.05). EPO was maintained at a high dose from the beginning of treatment to week 28 in the control group, whereas in the test group, EPO dose was reduced gradually. The response rate in the test group was higher than that in the control group (92.30 % vs 76.90 %; p < 0.05). Conclusion: Levocarnitine/iron saccharate combination had a significant positive effect on the treatment of renal anaemia. It effectively relieved oxidative stress reactions and reduced the dose of EPO required. Keywords: Haemodialysis, Renal anaemia, Oxidative stress reaction, Levocarnitine, Iron saccharate, Erythropoietin

Impact of anemia correction on the production of the circulating morphogenetic protein α-Klotho in patients with Stages 3B-4 chronic kidney disease: A new direction of cardionephroprotection

To investigate the impact of anemia correction with erythropoiesis stimulants on the serum level of the circulating morphogenetic protein α-Klotho in patients with Stages 3B--4 chronic kidney disease (CKD). 64 patients aged 42±8 years with Stages 3B--4 nondiabetic CKD were examined and divided into 2 groups: 1) 32 patients with anemia (the target hemoglobin levels could be achieved and kept with erythropoietin and iron saccharate in 20 patients (Group A) and those could not be done in 12 patients (Group 1B). A control group (Group 2) consisted of 32 non-anemic patients matched for gender, age, and degree of a glomerular filtration rate (GFR) reduction. Along with iron exchange indicators, the time course of changes in serum Klotho levels were examined in all the 64 patients during screening and one year after the end of the study. For correction of anemia, 32 patients with this condition (Groups 1A and 1B) took short-acting epoetin (hypodermic recormon 2,000 IU thrice per week + iron (intravenous venofer 5 ml of 100 mg once per week)) under control of hemoglobin levels and serum transferrin iron and ferritin saturation. After achieving the target hemoglobin level of 110-120 g/l, for its keeping, all the patients received, instead of short-acting epoetin, long-acting hypodermic darbepoetin-α 1.5 µg once every 2 months and intravenous iron saccharate 100 mg once every 2 weeks. Among the 32 anemic patients in Group 1, 20 (63%) (Group 1 A) could achieve the target hemoglobin level (110--120 g/l) and maintain it within this range, by performing therapy with epoitin-β + iron saccharate; anemia (the hemoglobin level of <110 g/l) persisted in 12 (37%) patients (Group 1B) despite the fact that epoetin and iron saccharate had been administered. Group 1A was noted to have an increase in α-Klotho concentrations by an average of 100±11.6-pg/ml as compared to Group 1B (by only 72±4.2 pg/ml). At the same time, the α-Klotho levels in the control group by the end of the follow-up decreased by an average of 210±12.9 pg/ml as compared to the prescreening value. There was a direct correlation between hemoglobin and serum ferritin concentrations and iron ferritin saturation percentage and α-Klotho levels. It was ascertained that the hemoglobin concentration of ≥110 g/l with a sensitivity of 89% and a specificity of 75% could predict higher serum α-Klotho levels in CKD. The same patients were found to have an inverse relationship between the serum level of α-Klotho and the risk of cardiovascular events. The serum level of the protein Klotho is not only a marker for the severity of CKD and its complications (anemia, left ventricular hypertrophy, and heart failure), but also a pathogenetic factor of CKD progression. Anemia correction with erythropoiesis stimulants has been shown to enhance the renal and extrarenal production of α-Klotho.

Intravenous Iron Saccharate Infusion for Treatment of Iron Deficiency Anemia before Labor

Intravenous Iron Saccharate Infusion for Treatment of Iron Deficiency Anemia before Labor

Metabolic response to subacute and subchronic iron overload in a rat model.

One of the common causes of iron overload is excessive iron intake in cases of iron-poor anemia, where iron saccharate complex (ISC) is routinely used to optimize erythropoiesis. However, non-standardized ISC administration could entail the risk of iron overload. To induce iron overload, Wistar rats were intraperitoneally injected with subacute (0.2 mg kg⁻¹) and subchronic (0.1 mg kg⁻¹) overdoses of ISC for 2 and 4 weeks, respectively. Iron status was displayed by an increase in transferrin saturation (up to 332%) and serum and liver iron burden (up to 19.3 μmol L⁻¹ and 13.2 μmol g⁻¹ wet tissue, respectively) together with a drop in total and unsaturated iron binding capacities "TIBC, UIBC" as surrogate markers of transferrin activity. Iron-induced leukocytosis (up to 140%), along with the decline in serum transferrin markers (up to 43%), respectively, mark positive and negative acute phase reactions. Chemical stress was demonstrated by a significant rise (p > 0.05) in indices of the hemogram (erythrocytes, hemoglobin, hematocrit, leukocytes) and stress metabolites [corticosterone (CORT) and lactate]. Yet, potential causes of the unexpected decline in serum activities of ALT, AST and LDH (p > 0.05) might include decreased hepatocellular enzyme production and/or inhibition or reduction of the enzyme activities. The current findings highlight the toxic role of elevated serum and liver iron in initiating erythropoiesis and acute phase reactions, modifying iron status and animal organ function, changing energy metabolism and bringing about accelerated glycolysis and impaired lactate clearance supposedly by decreasing anaerobic threshold and causing premature entering to the anaerobic system.

Oxidative stress and antioxidant response to subacute and subchronic iron overload in Wistar rat

Iron saccharate complex ISC is an iron supplement used to optimize erythropoiesis in cases of iron deficiencies. Because of the lack of major mechanisms of iron excretion, excess iron unbound to protective molecules is believed to be involved in catalyzing the generation of reactive oxygen species and induction of oxidative stress. This study employed ISC for the purpose of inducing iron overload and hence investigating the consequent iron toxicity, lipid peroxidation and antioxidant extent in a murine species. Male Wistar rats were given iron as intraperitoneal injections of ISC in subacute (0.2 mg Fe kg−1 for 2 weeks) and subchronic (0.1 mg Fe kg−1 for 4 weeks) doses. In iron-overloaded rats, enhanced hepatic iron accumulation (P > 0.001) attended by increased serum concentrations of malondialdehyde (MDA) (P > 0.001) and activities of antioxidant enzymes (superoxide dismutase SOD, catalase CAT and glutathione peroxidase GPx) (P > 0.001) was pointed out. The demonstrated antioxidant boost is attributed to a sense of equilibrium prompted by the potential of iron-induced oxidative stress to modify antioxidant defense capacity and to modulate susceptibility to oxidative stress. Rats seemed to constantly suffer from oxidative stress based on the consistent rise in MDA that was not overwhelmed by the elevated antioxidant input. The current findings are of informative value in drawing attention to the health hazards of applying higher doses of the commercially used iron supplement ISC. Data are virtually significant in elucidating the higher magnitude of subchronic than subacute iron overload in initiating oxidative stress and antioxidant defense. Both pathways proceeded in a time-dependent rather than dose-dependent manner.

Iron overload induces changes of pancreatic and duodenal divalent metal transporter 1 and prohepcidin expression in mice

It is well known that the iron content of the body is tightly regulated. Iron excess induces adaptive changes that are differentially regulated in each tissue. The pancreas is particularly susceptible to iron-related disorders. We studied the expression and regulation of key iron proteins in the pancreas, duodenum and liver, using an animal model of iron overload (female CF1 mice injected i.p. with iron saccharate, colloidal iron form). Divalent metal transporter 1, prohepcidin and ferritin (pancreas, duodenum, liver) were assessed by immunohistochemistry; divalent metal transporter 1 (pancreas, duodenum) by Western blot. In the iron overloaded mice, prohepcidin expression increased in islets of Langerhans and hepatocytes, and divalent metal transporter 1 expression decreased in cells of islets and in enterocytes. In the iron overloaded mice, ferritin expression decreased in islets of Langerhans and increased in acinar cells; hemosiderin was localized in connective tissue cells. The inverse relationship between divalent metal transporter 1 and prohepcidin may indicate a negative regulation by hepcidin, and hence reduction of iron stores in islets of Langerhans. Our data showed that in iron overloaded mice model, induced by colloidal iron form, a coordinated expression of key iron proteins in the pancreas, duodenum and liver may occur. Further research will be necessary to determine the adaptive responses induced by iron in the pancreas.

Erythropoiesis Stimulation in Patients with Postoperative Anemia

Early treatment for anemia with epoietin (EPO) and intravenous iron after replacement of the large lower extremity joints permits an 8 g/l increment in hemoglobin concentration to be achieved by postoperative day 10 versus day 2. Objective: to evaluate the efficiency of medical stimulation of erythropoiesis in the treatment of anemia after large joint replacement. Materials and methods. The medical records of patients who had undergone hip or knee joint replacement in January 2010 to August 2011 were retrospectively analyzed. Group 1 (EPO group) included 32 patients who postoperatively received iron saccharate 600 mg and subcutaneous epoietin alfa 40,000 IU. In Group 2 (IRON group), 27 patients took iron saccha-rate 600 mg without epoietin. In Group 3 (CON group) 62 patients had no parenteral erythropoietic stimulants. Blood hemoglobin levels on postoperative days 1, 2, and 10 were a main control indicator. Blood transfusion therapy was not performed in the identified groups. Results. In the first two days, hemoglobin levels were statistically significantly higher in the CON group than those in the EPO group and on day 10 intergroup differences were absent. By day 10 versus day 2, a statistically significant increase in hemoglobin concentrations was found in the EPO and IRON groups. In the EPO group, the hemoglobin concentration increment was significantly higher than that in the CON group. There were no clinical signs of thrombosis and thromboembolic events in the patients of the study groups. Conclusion. The co-administration of intravenous iron and epoietin enables an 8 g/l increase to be achieved on postoperative day 10 versus day 2. Key words: joint replacement, anemia, epoietin, iron saccharate, intravenous iron.

Effects of intravenous iron saccharate on improving severe anemia in rheumatoid arthritis patients

Anemia in rheumatoid arthritis (RA) is multifactorial. Iron deficiency, either definite or relative (defect in iron utilization), exists in RA patients with anemia. Intravenous iron therapy is indicated in severe and symptomatic cases or those with conditions precluding use of oral iron, but its safety and long-term efficacy have not been well-established. Forty severe anemic (hemoglobin < 9g/dL) RA patients with or without demonstrable bone marrow iron stain were enrolled in this study. Fractionated administration of intravenous iron saccharate was undertaken and the median follow-up time was 1year. All patients exhibited significant elevations of hemoglobin 3months after treatment, which were more pronounced in the nonstainable iron marrow subjects {median (interquartile range): 3.8 (2.9-4.8) g/dL versus 2.9 (2.0-3.0) g/dL, p < 0.01}. Thereafter, hemoglobin remained at a plateau level that lasted during the observation period. Throughout the whole course, none of the cases exhibited side effects or flare up of disease activities. The use of intravenous iron saccharate, preferably administrated in a fractionated way, is effective in the correction of severe anemia in RA patients, especially those with nonstainable iron marrow.

Influence of Vitamins, Trace Elements, and Iron on Lipid Peroxidation Reactions in All‐in‐One Admixtures for Neonatal Parenteral Nutrition

The purpose of this study was to evaluate the effect of vitamins, trace elements, or iron on lipid peroxidation in all-in-one parenteral nutrition (PN) admixtures for preterm neonates. Malondialdehyde (MDA) concentrations were analyzed over a 24-hour period (H1-H24) in lipid-containing PN solutions that have a composition identical to that used in the routine clinical care of preterm infants. Six different solutions were prepared and evaluated when exposed to ambient light and light-protected conditions as follows: control (without vitamins [Vit], trace elements [TE], or iron [Fe] [Vit-TE-Fe-]), solution 1 (Vit+TE+Fe-), solution 2 (Vit+TE-Fe-), solution 3 (Vit-TE+Fe-), solution 4 (Vit-TE-Fe+), and solution 5 (Vit+TE+Fe+). MDA concentrations in PN solutions were significantly higher at H24 than at H0 when they contained multivitamins (P < .001), trace elements (P = .002), or iron saccharate (P = .018). MDA concentration was particularly high when all 3 micronutrients were present (P < .001) or when the solutions were exposed to ambient light. In solutions containing iron, MDA concentrations were elevated at H0, and levels did not change whether protected from (P < .001) or exposed to (P < .001) from light. The addition of vitamins and trace elements to PN solutions induces a significant increase in peroxidation products, which are lowered when admixtures are protected from light. Iron should not be included in these solutions, even if solutions are light-protected. By following these conditions it is possible to use all-in-one admixtures in the nutrition management of preterm infants.