Evaluation of iron dextran application programs to prevent iron deficiency anemia in piglets / Avaliação de programas para aplicação de ferro dextrano na prevenção da anemia ferropriva de leitões

To evaluate the effect of different iron dextran application programs on the performance, fecal score, and skin color of suckling piglets, as well as sow performance, 288 piglets from 24 sows were allocated to four treatments in six replications with 12 piglets per experimental unit, in a block design. The treatments were as follows: T200_000, T200_100, T200_200, and T100_100, whose respective values (in mg) corresponded to the applications of the first dose of iron dextran on the second day of life and of the second dose on the 10th day. Piglets on T200_000 and T200_200 showed the highest feed intake. In the period from 10 to 22 days, piglets receiving T100_100 exhibited the highest fecal score. On the 10th day of age, the lowest lightness (L*) value on the ear was obtained with T200_100, and the highest with T100_100. Treatments T200_000, T200_100, and T200_200 generated the highest red color (a*) intensity on the ear, whereas T100_100 provided the lowest hue and parameter b* values on the leg and snout. On the 22nd day of age, the highest b* and hue values of the ear and snout were found in the group fed T100_100. In conclusion, all evaluated programs were efficient in preventing iron deficiency anemia in newborn piglets. To reduce expenses, we recommend administering a single dose of 200 mg of iron dextran to piglets on the second day of life.(AU)

Foram utilizados 288 leitões de 24 matrizes, distribuídos em delineamento em blocos com quatro tratamentos, seis repetições, com 12 leitões por unidade experimental com objetivo de avaliar diferentes programas de aplicação de ferro dextrano sobre desempenho, escore fecal e coloração de pele de leitões em aleitamento, assim como as repercussões sobre o desempenho das matrizes. Os tratamentos consistiram em: T200_000; T200_100; T200_200; e T100_100; nos quais os valores corresponderam, respectivamente (em mg), à aplicação da primeira dose de ferro dextrano no segundo dia de vida e à aplicação da segunda dose no 10º dia. Os leitões que foram submetidos a T200_000 e a T200_200 tiveram maior consumo de ração. No período de 10 a 22 dias, os leitões de T100_100 obtiveram maior escore fecal. Ao 10º dia de idade dos leitões, o menor valor de luminosidade (L*) da orelha foi em T200_100 e o maior valor em T100_100. A maior intensidade da cor vermelha (a*) na orelha foi obtida em T200_000, T200_100 e T200_200. Na tonalidade e no parâmetro b* do pernil e do focinho, T100_100 foi aquele que apresentou menor valor. No 22º dia de idade dos leitões, o maior valor de b* e da tonalidade da orelha e do focinho foi verificado em T100_100. Conclui-se que todos os programas avaliados foram eficientes na prevenção da anemia ferropriva em leitões neonatos. Visando a redução de gastos, recomenda-se a administração de uma única dose de 200 mg de ferro dextrano no segundo dia de vida dos leitões.(AU)

Diagnosis of Systemic Diseases Using Infrared Spectroscopy: Detection of Iron Overload in Plasma-Preliminary Study.

Despite the important role of iron in cellular homeostasis, iron overload (IO) is associated with systemic and tissue deposits which damage several organs. In order to reduce the impact caused by IO, invasive diagnosis exams (e.g., biopsies) and minimally invasive methods were developed including computed tomography and magnetic resonance imaging. However, current diagnostic methods are still time-consuming and expensive. A cost-effective solution is using Fourier-transform infrared spectroscopy (FTIR) for real-time and molecular-sensitive biofluid analysis during conventional laboratory exams. In this study, we performed the first evaluation of the accuracy of FTIR for IO diagnosis. The study was performed by collecting FTIR spectra of plasma samples of five rats intravenously injected with iron-dextran and five control rats. We developed a classification model based on principal component analysis and supervised methods including J48, random forest, multilayer perceptron, and radial basis function network. We achieved 100% accuracy for the classification of the IO status and provided a list of possible biomolecules related to the vibrational modes detected. In this preliminary study, we give a first step towards real-time diagnosis for acute IO or intoxication. Furthermore, we have expanded the literature knowledge regarding the pathophysiological changes induced by iron overload.

Trends in Anemia, Iron, Therapy, and Transfusion in Hospitalized Pediatric Patients with Inflammatory Bowel Disease.

OBJECTIVE: To evaluate trends in diagnosis and management of iron deficiency anemia using a large national children's hospital database in pediatric patients admitted with inflammatory bowel disease (IBD). STUDY DESIGN: In this retrospective multicenter cohort study, we used the Pediatric Health Information System de-identified administrative database. Patients age <21 years with ≥2 admissions with International Classification of Disease, Ninth Revision and Tenth Revision codes for Crohn's disease or ulcerative colitis from 2012 to 2018 were included. We extracted data regarding diagnoses of anemia and/or iron deficiency, and receipt of oral iron, intravenous (IV) iron, and/or blood transfusion. Data were analyzed descriptively. RESULTS: We identified 8007 unique patients meeting study criteria for a total of 28 260 admissions. The median age at admission was 15.4 years. A diagnosis of anemia was documented in 29.8% of admissions and iron studies were performed in 12.6%. IV iron was given in 6.3% of admissions and blood transfusions in 7.4%. The prevalence of the diagnosis of anemia among IBD admissions increased from 24.6% in 2012 to 32.4% in 2018 (P < .0001). There was a steady increase in the proportion of IBD admissions that used IV iron, from 3.5% in 2012 to 10.4% in 2018 (P < .0001), and the proportion of admissions with red cell transfusions decreased over time from 9.4% to 4.4% (P < .0001). CONCLUSIONS: Iron deficiency anemia is prevalent among pediatric patients with IBD admitted to US children's hospitals. From 2012 to 2018, there was an increase in the use of inpatient IV iron for the treatment of iron deficiency anemia and a decrease in transfusions.

High Prevalence of Iron Deficiency Despite Standardized High-Dose Iron Supplementation During Recombinant Erythropoietin Therapy in Extremely Low Gestational Age Newborns.

OBJECTIVE: To assess the effects of protocolized recombinant human erythropoietin (r-HuEPO) therapy and standardized high dose iron supplementation on hematologic and iron status measures in a cohort of extremely low gestational age newborns (ELGANs). STUDY DESIGN: Charts of extremely low gestational age newborns admitted from 2006 to 2016 and who had received r-HuEPO per neonatal intensive care unit protocol were reviewed. The r-HuEPO was started at a dose of 900 IU/kg per week after 7 days of age and continued until 35 weeks postmenstrual age. Oral iron supplementation at 6-12 mg/kg per day was used to maintain a transferrin saturation of >20% during r-HuEPO treatment. Data on demographic features, hematologic and iron panel indices, red blood cell transfusions, and clinical outcomes were collected. Quartile groups were created based on serum ferritin levels at the conclusion of the r-HuEPO treatment and the quartiles were compared. RESULTS: The cohort included 116 infants with mean gestational age 25.8 ± 1.5 weeks and birth weight 793 ± 174.1 g. The r-HuEPO promoted erythropoiesis as indicated by increasing hemoglobin, hematocrit, and reticulocyte count. Serum ferritin decreased over time and was ≤75 ng/mL in 60.2% of infants at the conclusion of r-HuEPO therapy; 87% received packed red blood cell transfusions. Transfusion volume, total iron intake, total iron binding capacity, and transferrin concentration differed among infants in the different serum ferritin quartiles (P < .05). CONCLUSIONS: In extremely low gestational age newborns, r-HuEPO therapy promoted erythropoiesis. Despite a biomarker-based standardized high-dose iron supplementation, the majority of infants had evidence of iron deficiency to a degree that is associated with reduced brain function.

Chronic Iron Overload Restrains the Benefits of Aerobic Exercise to the Vasculature.

Physical exercise is a well-recognized effective non-pharmacological therapy for cardiovascular diseases. However, because iron is essential element in many physiological processes including hemoglobin and myoglobin synthesis, thereby playing a role on oxygen transport, many athletes use iron supplement to improve physical performance. Regarding this, iron overload is associated with oxidative stress and damage to various systems, including cardiovascular. Thus, we aimed to identify the vascular effects of aerobic exercise in a rat model of iron overload. Male Wistar rats were treated with 100 mg/kg/day iron-dextran, i.p., 5 days a week for 4 weeks, and then underwent aerobic exercise protocol on a treadmill at moderate intensity, 60 min/day, 5 days a week for 8 weeks. Exercise reduced vasoconstrictor response of isolated aortic rings by increasing participation of nitric oxide (NO) and reducing oxidative stress, but these benefits to the vasculature were not observed in rats previously subjected to iron overload. The reduced vasoconstriction in the exercised group was reversed by incubation with superoxide dismutase (SOD) inhibitor, suggesting that increased SOD activity by exercise was lost in iron overload rats. Iron overload groups increased serum levels of iron, transferrin saturation, and iron deposition in the liver, gastrocnemius muscle, and aorta, and the catalase was overexpressed in the aorta probably as a compensatory mechanism to the increased oxidative stress. In conclusion, despite the known beneficial effects of aerobic exercise on vasculature, our results indicate that previous iron overload impeded the anticontractile effect mediated by increased NO bioavailability and endogenous antioxidant response due to exercise protocol.

Chronic iron overload induces vascular dysfunction in resistance pulmonary arteries associated with right ventricular remodeling in rats.

Although iron excess is toxic to the vasculature and even that pulmonary hypertension has been reported in this scenario, the role of iron overload per se remains to be clarified. This study aimed to test the effects of chronic iron-overload in rats on the morphophysiology of resistance pulmonary arteries (RPA) and right ventricle (RV) remodeling. Rats were injected with saline or iron-dextran (10, 100 and 200 mg/kg/day i.p.) for 28 days. Our results indicated increased circulating iron with significant lung deposits. Moreover, rats treated with the highest dose exhibited RV dysfunction and hypertrophy; inward remodeling and increased vasoconstriction of the RPA. Vascular hyperreactivity was accompanied by reduced nitric oxide (NO), and was reversed by incubation with Dimethylsulfoxide, Catalase and Tempol. The NADPH oxidase subunit gp91phox was increased due to iron-overload, and incubation with angiotensin II type-1 receptor (AT1) antagonist losartan not only reduced oxidative stress but also restored vascular function. Thus, we concluded that AT1 pathway plays a role in pulmonary vascular dysfunction by increasing oxidative stress and reducing NO bioavailability, thereby contributing to vascular remodeling and pulmonary hypertension of iron-overload. This finding should instigate future studies on the beneficial impacts of in vivo blockade of AT1 receptor under iron overload.

Differential Effect of Acute Iron Overload on Oxidative Status and Antioxidant Content in Regions of Rat Brain.

The hypothesis of this study is that the cerebral cortex, hippocampus, and striatum of the rat brain are differentially affected in terms of oxidative stress and antioxidant capacity by acute Fe overload because Fe is distributed in a heterogeneous fashion among different regions and cells of the brain. The effects on the lipophilic and hydrophilic cellular environment were compared between regions and with the whole brain. A single dose of Fe-dextran increased Fe deposits, reaching a maximum after 6 hr. Both in whole brain and in cortex region, the ascorbyl/ascorbate content ratio was increased after 6 hr of Fe administration, while in striatum and hippocampus, there was no significant changes after Fe overload. Total thiol content decreased in whole brain and cortex, while there were no significant changes in striatum and hippocampus after Fe overload. The content of α-tocopherol (α-T), whether measured in the whole brain or in the isolated regions, did not change following Fe treatment. Lipid radical (LR•) generation rate after Fe-dextran overload only increased in the cortex region. The LR•/α-T content ratio was increased by Fe treatment in cortex but not in the whole brain, striatum, or hippocampus, in agreement with the study tested hypothesis.

Diferentes fontes de ferro na prevenção da anemia ferropriva e no desempenho de leitões lactentes / Different sources of iron for the prevention of iron deficiency anemia and performance of suckling piglets

Com o objetivo de avaliar o uso de diferentes fontes de ferro na prevenção da anemia ferropriva e no desempenho em leitões lactentes, dividiram-se 202 leitões em cinco tratamentos: FD - aplicação intramuscular de 200mg de ferro dextrano no terceiro dia de idade; T24 - terra à vontade fornecida aos leitões a cada 24 horas do terceiro ao 19º dia; T48 - terra à vontade fornecida aos leitões a cada 24 horas do terceiro ao 10º dia e do 11º ao 19º dia, com intervalo de 48 horas; T72 - terra à vontade fornecida aos leitões a cada 24 horas do terceiro ao 10º dia e do 11º ao 19º dia, com intervalo de 72 horas; SA - suplemento alimentar ultraprecoce rico em ferro quelatado em pó (SAUP) fornecido do terceiro ao 11º dia, com intervalo de 48 horas. O ferro dextrano aplicado no terceiro dia de vida e a suplementação com terra e SAUP foram eficientes para garantir o desempenho de leitões no período de aleitamento e não influenciaram no consumo de ração nem na taxa de viabilidade. As diferentes fontes de ferro estudadas não influenciaram o leucograma e foram eficientes na prevenção da anemia ferropriva e no desempenho dos leitões lactentes. Com relação às concentrações de hemoglobina e hematócrito, os animais suplementados com ferro dextrano apresentaram valores superiores quando comparados aos que recebem terra e SAUP.(AU)

In order to evaluate the use of different sources of iron to prevent iron deficiency anemia and to appraise the performance of suckling piglets, we sorted 202 piglets in five treatments. ID - intramuscular injection of 200mg of iron dextran on the third day of age; T24 - free daily access to land provided to piglets every 24 hours from the third to the nineteenth day; T48 - free daily access to land provided to piglets every 24 hours from the third to the tenth day and from day 11 to day 19 with an interval of 48 hours; T72 - free daily access to land provided to piglets every 24 hours from the third to the tenth day and from day 11 to day 19 with an interval of 72 hours; FS - Food supplement rich in iron-chelating powder (SAUP) available from the third to the eleventh day with an interval of 48 hours. The iron dextran applied on the third day of life as well as the supplementation with land and SAUP were effective to ensure the performance of piglets during the lactation period and did not affect feed intake or the viability rate. The different sources of iron studied did not influence the WBC (White Blood Cell) and succeded in preventing iron deficiency anemia and performance of suckling piglets. Regarding the concentrations of hemoglobin and hematocrit, the animals supplemented with iron dextran showed higher values when compared to those who receive land and SAUP.(AU)

Diferentes fontes de ferro na prevenção da anemia ferropriva e no desempenho de leitões lactentes / Different sources of iron for the prevention of iron deficiency anemia and performance of suckling piglets

Com o objetivo de avaliar o uso de diferentes fontes de ferro na prevenção da anemia ferropriva e no desempenho em leitões lactentes, dividiram-se 202 leitões em cinco tratamentos: FD - aplicação intramuscular de 200mg de ferro dextrano no terceiro dia de idade; T24 - terra à vontade fornecida aos leitões a cada 24 horas do terceiro ao 19º dia; T48 - terra à vontade fornecida aos leitões a cada 24 horas do terceiro ao 10º dia e do 11º ao 19º dia, com intervalo de 48 horas; T72 - terra à vontade fornecida aos leitões a cada 24 horas do terceiro ao 10º dia e do 11º ao 19º dia, com intervalo de 72 horas; SA - suplemento alimentar ultraprecoce rico em ferro quelatado em pó (SAUP) fornecido do terceiro ao 11º dia, com intervalo de 48 horas. O ferro dextrano aplicado no terceiro dia de vida e a suplementação com terra e SAUP foram eficientes para garantir o desempenho de leitões no período de aleitamento e não influenciaram no consumo de ração nem na taxa de viabilidade. As diferentes fontes de ferro estudadas não influenciaram o leucograma e foram eficientes na prevenção da anemia ferropriva e no desempenho dos leitões lactentes. Com relação às concentrações de hemoglobina e hematócrito, os animais suplementados com ferro dextrano apresentaram valores superiores quando comparados aos que recebem terra e SAUP.(AU)

In order to evaluate the use of different sources of iron to prevent iron deficiency anemia and to appraise the performance of suckling piglets, we sorted 202 piglets in five treatments. ID - intramuscular injection of 200mg of iron dextran on the third day of age; T24 - free daily access to land provided to piglets every 24 hours from the third to the nineteenth day; T48 - free daily access to land provided to piglets every 24 hours from the third to the tenth day and from day 11 to day 19 with an interval of 48 hours; T72 - free daily access to land provided to piglets every 24 hours from the third to the tenth day and from day 11 to day 19 with an interval of 72 hours; FS - Food supplement rich in iron-chelating powder (SAUP) available from the third to the eleventh day with an interval of 48 hours. The iron dextran applied on the third day of life as well as the supplementation with land and SAUP were effective to ensure the performance of piglets during the lactation period and did not affect feed intake or the viability rate. The different sources of iron studied did not influence the WBC (White Blood Cell) and succeded in preventing iron deficiency anemia and performance of suckling piglets. Regarding the concentrations of hemoglobin and hematocrit, the animals supplemented with iron dextran showed higher values when compared to those who receive land and SAUP.(AU)

Sub-chronic iron overload triggers oxidative stress development in rat brain: implications for cell protection.

This work was aimed to test the hypothesis that sub-chronic administration of iron-dextran (Fe-dextran) (six doses of 50 mg Fe-dextran/kg) to rats triggers a transient oxidative stress in brain and mechanisms of cellular antioxidant defence. After 2 h of administration of the 6th dose, a significant increase of total Fe, the labile Fe pool (LIP), the lipid radical (LR(•))/α-tocopherol (α-T) content ratio were observed, as compared to values in control brain homogenates. The ascorbyl radical (A(•))/ascorbate (AH(-)) content ratio and the oxidation rate of 2',7'-dichlorodihidrofluorescein (DCFH-DA) were significantly higher in Fe-dextran treated rats, as compared to values in brain from control rats after 4 h treatment. An increase in both catalase (CAT) and superoxide dismutase (SOD) activity was observed at 8 and 1-2 h, respectively. No significant changes were detected in the nuclear factor-κB (NF-κB) levels in nuclear extracts from rat brains after 1-8 h of Fe-dextran administration. After 2 h of Fe administration Fe concentration in cortex, striatum and hippocampus was significantly increased as compared to the same areas from control animals. Both, CAT and SOD activities were significantly increased in cortex after Fe administration over control values, without changes in striatum and hippocampus. Taken as a whole, sub-chronic Fe administration enhances the steady state concentration of Fe in the brain LIP that favors the settlement of an initial oxidative stress condition, both at hydrophilic and lipophilic compartments, resulting in cellular protection evidenced by antioxidant enzyme upregulation.

Iron dextran increases hepatic oxidative stress and alters expression of genes related to lipid metabolism contributing to hyperlipidaemia in murine model.

The objective of this study was to investigate the effects of iron dextran on lipid metabolism and to determine the involvement of oxidative stress. Fischer rats were divided into two groups: the standard group (S), which was fed the AIN-93M diet, and the standard plus iron group (SI), which was fed the same diet but also received iron dextran injections. Serum cholesterol and triacylglycerol levels were higher in the SI group than in the S group. Iron dextran was associated with decreased mRNA levels of pparα, and its downstream gene cpt1a, which is involved in lipid oxidation. Iron dextran also increased mRNA levels of apoB-100, MTP, and L-FABP indicating alterations in lipid secretion. Carbonyl protein and TBARS were consistently higher in the liver of the iron-treated rats. Moreover, a significant positive correlation was found between oxidative stress products, lfabp expression, and iron stores. In addition, a negative correlation was found between pparα expression, TBARS, carbonyl protein, and iron stores. In conclusion, our results suggest that the increase observed in the transport of lipids in the bloodstream and the decreased fatty acid oxidation in rats, which was promoted by iron dextran, might be attributed to increased oxidative stress.

Nitrosative Stress and Apoptosis by Intravenous Ferumoxytol, Iron Isomaltoside 1000, Iron Dextran, Iron Sucrose, and Ferric Carboxymaltose in a Nonclinical Model.

Iron is involved in the formation as well as in the scavenging of reactive oxygen and nitrogen species. Thus, iron can induce as well as inhibit both oxidative and nitrosative stress. It also has a key role in reactive oxygen and nitrogen species-mediated apoptosis. We assessed the differences in tyrosine nitration and caspase 3 expression in the liver, heart, and kidneys of rats treated weekly with intravenous ferumoxytol, iron isomaltoside 1000, iron dextran, iron sucrose and ferric carboxymaltose (40 mg iron/kg body weight) for 5 weeks. Nitrotyrosine was quantified in tissue homogenates by Western blotting and the distribution of nitrotyrosine and caspase 3 was assessed in tissue sections by immunohistochemistry. Ferric carboxymaltose and iron sucrose administration did not result in detectable levels of nitrotyrosine or significant levels of caspase 3 vs. control in any of the tissue studied. Nitrotyrosine and caspase 3 levels were significantly (p<0.01) increased in all assessed organs of animals treated with iron dextran and iron isomaltoside 1000, as well as in the liver and kidneys of ferumoxytol-treated animals compared to isotonic saline solution (control). Nitrotyrosine and caspase 3 levels were shown to correlate positively with the amount of Prussian blue-detectable iron(III) deposits in iron dextran- and iron isomaltoside 1000-treated rats but not in ferumoxytol-treated rats, suggesting that iron dextran, iron isomaltoside 1000 and ferumoxytol induce nitrosative (and oxidative) stress as well as apoptosis via different mechanism(s).

Iron toxicity mediated by oxidative stress enhances tissue damage in an animal model of diabetes.

Although iron is a first-line pro-oxidant that modulates clinical manifestations of various systemic diseases, including diabetes, the individual tissue damage generated by active oxidant insults has not been demonstrated in current animal models of diabetes. We tested the hypothesis that oxidative stress is involved in the severity of the tissues injury when iron supplementation is administered in a model of type 1 diabetes. Streptozotocin (Stz)-induced diabetic and non-diabetic Fischer rats were maintained with or without a treatment consisting of iron dextran ip at 0.1 mL day(-1) doses administered for 4 days at intervals of 5 days. After 3 weeks, an extensive increase (p < 0.001) in the production of reactive oxygen species (ROS) in neutrophils of the diabetic animals on iron overload was observed. Histological analysis revealed that this treatment also resulted in higher (p < 0.05) tissue iron deposits, a higher (p < 0.001) number of inflammatory cells in the pancreas, and apparent cardiac fibrosis, as shown by an increase (p < 0.05) in type III collagen levels, which result in dysfunctional myocardial. Carbonyl protein modification, a marker of oxidative stress, was consistently higher (p < 0.01) in the tissues of the iron-treated rats with diabetes. Moreover, a significant positive correlation was found between ROS production and iron pancreas stores (r = 0.42, p < 0.04), iron heart stores (r = 0.54, p < 0.04), and change of the carbonyl protein content in pancreas (r = 0.49, p < 0.009), and heart (r = 0.48, p < 0.02). A negative correlation was still found between ROS production and total glutathione content in pancreas (r = -0.50, p < 0.03) and heart (r = -0.45, p < 0.04). In conclusion, our results suggest that amplified toxicity in pancreatic and cardiac tissues in rats with diabetes on iron overload might be attributed to increased oxidative stress.

Acute iron overload and oxidative stress in brain.

An in vivo model in rat was developed by intraperitoneally administration of Fe-dextran to study oxidative stress triggered by Fe-overload in rat brain. Total Fe levels, as well as the labile iron pool (LIP) concentration, in brain from rats subjected to Fe-overload were markedly increased over control values, 6h after Fe administration. In this in vivo Fe overload model, the ascorbyl (A)/ascorbate (AH(-)) ratio, taken as oxidative stress index, was assessed. The A/AH(-) ratio in brain was significantly higher in Fe-dextran group, in relation to values in control rats. Brain lipid peroxidation indexes, thiobarbituric acid reactive substances (TBARS) generation rate and lipid radical (LR) content detected by Electron Paramagnetic Resonance (EPR), in Fe-dextran supplemented rats were similar to control values. However, values of nuclear factor-kappaB deoxyribonucleic acid (NFκB DNA) binding activity were significantly increased (30%) after 8h of Fe administration, and catalase (CAT) activity was significantly enhanced (62%) 21h after Fe administration. Significant enhancements in Fe content in cortex (2.4 fold), hippocampus (1.6 fold) and striatum (2.9 fold), were found at 6h after Fe administration. CAT activity was significantly increased after 8h of Fe administration in cortex, hippocampus and striatum (1.4 fold, 86, and 47%, respectively). Fe response in the whole brain seems to lead to enhanced NF-κB DNA binding activity, which may contribute to limit oxygen reactive species-dependent damage by effects on the antioxidant enzyme CAT activity. Moreover, data shown here clearly indicate that even though Fe increased in several isolated brain areas, this parameter was more drastically enhanced in striatum than in cortex and hippocampus. However, comparison among the net increase in LR generation rate, in different brain areas, showed enhancements in cortex lipid peroxidation, without changes in striatum and hippocampus LR generation rate after 6h of Fe overload. This information has potential clinical relevance, as it could be the key to understand specific brain damage occurring in conditions of Fe overload.

Spondias pinnata stem bark extract lessens iron overloaded liver toxicity due to hemosiderosis in Swiss albino mice.

The present study was designed to evaluate the ameliorating effect of 70% methanol extract of Spondias pinnata (SPME) on iron overload induced liver injury. Iron overload was induced by intraperitoneal administration of iron-dextran into mice and resulting liver damage was manifested by significant rise in serum enzyme markers (ALT, AST, ALP and bilirubin) and reduction in liver antioxidants (SOD, CAT, GST and GSH). Hepatic iron, serum ferritin, lipid peroxidation, protein carbonyl and hydroxyproline contents were measured in response to the oral administration of SPME of different doses (50, 100 and 200 mg/kg body weight). In order to determine the efficiency as iron chelating drug, the release of iron from ferritin by SPME was further studied. Enhanced levels of antioxidant enzymes were detected in SPME treated mice. SPME produced a dose dependent inhibition of lipid peroxidation, protein oxidation, liver fibrosis; and levels of serum enzyme markers and ferritin were also reduced dose dependently. The liver iron content was also found to be less in SPME treated group compared to control group. The reductive release of ferritin iron was augmented significantly after dose dependent addition of SPME. The ameliorating effect of SPME on damaged liver was furthermore supported by the histopathological studies that showed improved histological appearances. In conclusion, the present results demonstrate the hepatoprotective efficiency of SPME in iron intoxicated mice, and hence possibly useful as iron chelating drug for iron overload diseases.

[Experience in kidney transplantation without blood transfusion: kidney transplantation transfusion-free in Jehovah's Witnesses. First communication in Mexico]. / Experiencia en trasplante renal sin transfusión sanguínea en Testigos de Jehová, Primera comunicación en México.

BACKGROUND: Jehovah's Witness refuse blood transfusion, but they accept organ transplantation, albumin, immunoglobulin, vaccines and clotting factors. CLINICAL CASES: We present 3 kidney transplants in Jehovah's Witness patients (two male and one female) without blood transfusion, with a mean age of 31.33 years and a mean body mass index of 20.99 kg/m(2). All patients underwent pretransplant peritoneal dialysis for an average of 52.3 months. Two transplants came from living donors and one from a deceased donor with a cold ischemia of 23 hours. The donors were two females and one male, with a mean age of 34.33 years. All patients received pretransplant erythropoietin and iron dextran and an intraoperative cell saver was used. Hemoglobin, hematocrit, red blood cells and serum creatinine levels, as well as the glomerular filtration at 24 months postransplant were stable. All patients received induction with basiliximab and initial immunosuppression with calcineurin inhibitors. One of the patients had a perirenal hematoma as a complication, which required a surgery 20 days post-transplant. At 5, 26 and 36 months postransplant the three patients are alive and with functional grafts. CONCLUSION: It is possible to perform kidney transplantation without transfusion in Jehovah's Witness, obtaining an acceptable global survival without acute rejection.

Antecedentes: los Testigos de Jehová rechazan la transfusión sanguínea, pero aceptan el trasplante de órganos, albúmina, inmunoglobulina, vacunas y factores de coagulación. Casos clínicos: comunicamos tres casos de pacientes (dos masculinos y uno femenino) a quienes se realizó trasplante renal en Testigos de Jehová sin transfusión sanguínea, con edad promedio de 31.33 años e índice de masa corporal promedio de 20.99 kg/m2. Los tres pacientes recibieron diálisis peritoneal pre trasplante por un promedio de 52.3 meses. Se realizaron dos trasplantes de donante vivo y uno de fallecido, con isquemia fría de 23 horas. Los donantes fueron dos femeninos y uno masculino, con edad promedio de 34.33 años. Los tres pacientes recibieron eritropoyetina y hierro dextrán pretrasplante y en el transoperatorio se utilizó una máquina de recuperación celular. Las concentraciones de hemoglobina, hematócrito, glóbulos rojos, creatinina sérica y filtración glomerular a 24 meses postrasplante permanecieron estables. La inducción se realizó con basiliximab y la inmunosupresión inicial con inhibidores de calcineurina. Uno de los pacientes tuvo como complicación un hematoma perirrenal que ameritó reintervención a los 20 días postrasplante. A 5, 26 y 36 meses postrasplante los tres pacientes están vivos y con injerto funcional. Conclusión: es posible realizar trasplantes renales sin transfusión sanguínea en Testigos de Jehová, con supervivencia global aceptable y sin episodios de rechazo agudo.

Evaluation of toxicity and oxidative stress induced by intravenous iron isomaltoside 1000 in a nonclinical model.

The physicochemical characteristics of intravenous iron complexes affect the extent of weakly-bound iron and thus the degree of oxidative stress. The new preparation iron isomaltoside 1000 (IIM) was compared to iron sucrose (IS) and a control group in terms of biochemistry, oxidative stress, inflammatory markers and iron deposition in the liver, heart and kidneys of healthy rats. Renal function was significantly impaired in the IIM group versus both IS and controls. Liver enzymes were also significantly higher in IIM-treated animals versus the other groups, indicative of hepatic injury. Systolic blood pressure was significantly lower following IIM administration compared to IS or control animals. Oxidative stress in the liver, heart and kidneys was greater in the IIM group, as indicated by significantly increased levels of malondialdehyde and antioxidant enzyme activity, accompaniedby a significantly lower ratio of reduced to oxidized glutathione. Microscopy demonstrated more extensive positive staining for iron, and a smaller area of ferritin staining, in the liver, heart and kidneys of rats treated with IIM versus IS.Levels of the inflammatory markers TNF-alpha and IL6 were both significantly higher in the IIM group versus IS in all assessed tissues. These findings indicate that IIM has a less favorable safety profile than IS in healthy rats, adversely affecting iron deposition, oxidative stress and inflammatory responses, with impaired liver and renal function.

Fe allocation in liver during early stages of endotoxemia in Fe-overload rats.

The hypothesis of this study was that alterations in Fe distribution triggered by lipopolysaccharide (LPS) administration were affected in vivo by Fe overload. Lipopolysaccharide treatment by itself significantly decreased Fe content in serum and increased the blood NO-hemoglobin (NO-Hb) EPR signal and nitrotyrosine protein content in liver, as compared to values in control animals. Fe overload (produced by Fe-dextran ip administration) caused an increase, as compared to values in control animals, in Fe content in serum, and a significant enhancement in ferritin (Ft) content, Fe content in Ft, the labile Fe pool (LIP), and the protein carbonyl content in the liver. The simultaneous administration of LPS and Fe-dextran lead to a significant increase in the Fe content in serum, blood NO-Hb EPR signal, the content of Fe, Fe in Ft, LIP, protein carbonyl, and nitrotyrosine protein in liver, as compared to values in control animals. The data reported here indicate that the protective strategy against endotoxemia of sequestering serum Fe content is not fully operative under Fe overload conditions. However, the oxidative condition of the liver does not seem to be being affected, since endogenous mechanisms were able to regulate the amount of catalytically active Fe to the same levels observed after Fe-dextran administration, even in the presence of LPS, over the initial six-hour period.

Assessment of the extent of oxidative stress induced by intravenous ferumoxytol, ferric carboxymaltose, iron sucrose and iron dextran in a nonclinical model.

Intravenous (i.v.) iron is associated with a risk of oxidative stress. The effects of ferumoxytol, a recently approved i.v. iron preparation, were compared with those of ferric carboxymaltose, low molecular weight iron dextran and iron sucrose in the liver, kidneys and heart of normal rats. In contrast to iron sucrose and ferric carboxymaltose, low molecular weight iron dextran and ferumoxytol caused renal and hepatic damage as demonstrated by proteinuria and increased liver enzyme levels. Higher levels of oxidative stress in these tissues were also indicated, by significantly higher levels of malondialdehyde, significantly increased antioxidant enzyme activities, and a significant reduction in the reduced to oxidized glutathione ratio. Inflammatory markers were also significantly higher with ferumoxytol and low molecular weight iron dextran rats than iron sucrose and ferric carboxymaltose. Polarographic analysis suggested that ferumoxytol contains a component with a more positive reduction potential, which may facilitate iron-catalyzed formation of reactive oxygen species and thus be responsible for the observed effects. Only low molecular weight iron dextran induced oxidative stress and inflammation in the heart.