RESUMEN
BACKGROUND: Iron (Fe) supplementation is a critical component of anemia therapy for patients with chronic kidney disease (CKD). However, serum Fe, ferritin, and transferrin saturation, used to guide Fe replacement, are far from optimal, as they can be influenced by malnutrition and inflammation. Currently, there is a trend of increasing Fe supplementation to target high ferritin levels, although the long-term risk has been overlooked. METHODS: We prospectively enrolled 28 patients with CKD on hemodialysis with high serum ferritin (> 1000 ng/ml) and tested the effects of 1-year deferoxamine treatment, accompanied by withdrawal of Fe administration, on laboratory parameters (Fe status, inflammatory and CKD-MBD markers), heart, liver, and iliac crest Fe deposition (quantitative magnetic resonance imaging [MRI]), and bone biopsy (histomorphometry and counting of the number of Fe positive cells in the bone marrow). RESULTS: MRI parameters showed that none of the patients had heart iron overload, but they all presented iron overload in the liver and bone marrow, which was confirmed by bone histology. After therapy, ferritin levels decreased, although neither hemoglobin levels nor erythropoietin dose was changed. A significant decrease in hepcidin and FGF-23 levels was observed. Fe accumulation was improved in the liver and bone marrow, reaching normal values only in the bone marrow. No significant changes in turnover, mineralization or volume were observed. CONCLUSIONS: Our data suggest that treatment with deferoxamine was safe and could improve Fe accumulation, as measured by MRI and histomorphometry. Whether MRI is considered a standard tool for investigating bone marrow Fe accumulation requires further investigation. Registry and the registration number of clinical trial: ReBEC (Registro Brasileiro de Ensaios Clinicos) under the identification RBR-3rnskcj available at: https://ensaiosclinicos.gov.br/pesquisador.
Asunto(s)
Médula Ósea , Deferoxamina , Ferritinas , Sobrecarga de Hierro , Hierro , Hígado , Diálisis Renal , Humanos , Masculino , Femenino , Sobrecarga de Hierro/tratamiento farmacológico , Sobrecarga de Hierro/etiología , Sobrecarga de Hierro/metabolismo , Médula Ósea/metabolismo , Médula Ósea/efectos de los fármacos , Médula Ósea/patología , Ferritinas/sangre , Ferritinas/metabolismo , Hígado/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Hígado/diagnóstico por imagen , Persona de Mediana Edad , Deferoxamina/uso terapéutico , Deferoxamina/administración & dosificación , Hierro/metabolismo , Anciano , Imagen por Resonancia Magnética , Estudios Prospectivos , Insuficiencia Renal Crónica/terapia , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/sangre , Factor-23 de Crecimiento de Fibroblastos , Hepcidinas/metabolismoRESUMEN
BACKGROUND/OBJECTIVES: Sickle cell anemia (SCA) is marked by hypoxia, inflammation, and secondary iron overload (IO), which potentially modulate hepcidin, the pivotal hormone governing iron homeostasis. The aim was to evaluate the iron incorporation in red blood cells (RBC) in SCA pediatric patients, considering the presence or absence of IO. SUBJECTS/METHODS: SCA children (n = 12; SCAtotal) ingested an oral stable iron isotope (57Fe) and iron incorporation in RBC was measured after 14 days. Patients with ≥1000 ng/mL serum ferritin were considered to present IO (SCAio+; n = 4) while the others were classified as being without IO (SCAio-; n = 8). Liver iron concentration (LIC) was determined by Magnetic Resonance Imaging (MRI) T2* method. RESULTS: The SCAio+ group had lower iron incorporation (mean ± SD: 0.166 ± 0.04 mg; 3.33 ± 0.757%) than SCAio- patients (0.746 ± 0.303 mg; 14.9 ± 6.05%) (p = 0.024). Hepcidin was not different between groups. Iron incorporation was inversely associated with serum ferritin level (SCAtotal group: r = -0.775, p = 0.041; SCAio- group: r = -0.982; p = 0.018) and sickle hemoglobin (HbS) presented positive correlation with iron incorporation (r = 0.991; p = 0.009) in SCAio- group. LIC was positively associated with ferritin (SCAtotal: r = 0.921; p = 0.026) and C reactive protein (SCAio+: r = 0.999; p = 0.020). CONCLUSION: SCAio+ group had lower iron incorporation in RBC than SCAio- group, suggesting that they may not need to reduce their intake of iron-rich food, as usually recommended. Conversely, a high percentage of HbS may indirectly exacerbate hypoxia and seems to increase iron incorporation in RBC. TRIAL REGISTRATION: This trial was registered at www.ensaiosclinicos.gov.br . Identifier RBR-4b7v8pt.
Asunto(s)
Anemia de Células Falciformes , Eritrocitos , Ferritinas , Hepcidinas , Isótopos de Hierro , Sobrecarga de Hierro , Hierro , Humanos , Anemia de Células Falciformes/sangre , Proyectos Piloto , Eritrocitos/metabolismo , Niño , Masculino , Femenino , Ferritinas/sangre , Hierro/sangre , Hierro/metabolismo , Sobrecarga de Hierro/sangre , Adolescente , Hepcidinas/sangre , Hígado/metabolismoRESUMEN
PURPOSE: Iron absorption in sickle cell anemia (SCA) remains unclear and studies in adults with SCA are scarce. The aim of this study was to evaluate the iron absorption SCA adults and its association with iron status and hepcidin concentration. METHODS: SCA patients (n = 13; SCAtotal) and control participants (n = 10) ingested an oral stable iron isotope (57Fe). Iron absorption was measured by inductively coupled plasma mass spectrometry (ICP-MS) 14 days after isotope administration. Patients with ≥ 1000 ng/mL serum ferritin were considered to present iron overload (IO) (SCAio+; n = 3) and others classified without IO (SCAio-; n = 10). RESULTS: Iron absorption in the control group ranged from 0.3 to 26.5% (median = 0.9%), while it varied from 0.3 to 5.4% in SCAio+ (median = 0.5%) and from 0.3 to 64.2% in the SCAio- (median = 6.9%). Hepcidin median values were 14.1 ng/mL (3.0-31.9 ng/mL) in SCAio-, 6.2 ng/mL (3.3-7.8 ng/mL) in SCAio + and 6.2 ng/mL (0.6-9.3 ng/mL) in control. Iron absorption was associated with ferritin level (r = - 0.641; p = 0.018) and liver iron concentration (LIC; r = - 0.786; p = 0.036) in the SCAtotal group. CONCLUSION: Our data suggest that SCAio- individuals may be at risk of developing primary IO. Simultaneously, secondary IO may induce physiological adaptation, resulting in reduced iron absorption. Further studies evaluating intestinal iron absorption using larger sample sizes should be conducted to help establish a safe nutrition approach to be adopted and to ensure the security of food-fortifying public policies for these patients. TRIAL REGISTRATION: This trial was registered at www.ensaiosclinicos.gov.br (Identifier RBR-4b7v8pt).
Asunto(s)
Anemia de Células Falciformes , Hepcidinas , Absorción Intestinal , Isótopos de Hierro , Humanos , Anemia de Células Falciformes/sangre , Adulto , Masculino , Femenino , Isótopos de Hierro/farmacocinética , Hepcidinas/sangre , Adulto Joven , Ferritinas/sangre , Hierro/sangre , Hierro/farmacocinética , Hierro/metabolismo , Sobrecarga de Hierro , Hierro de la Dieta/farmacocinética , Hierro de la Dieta/administración & dosificación , Persona de Mediana Edad , Estado NutricionalRESUMEN
Obesity is associated with dysfunctions in hypothalamic neurons that regulate metabolism, including agouti-related protein (AgRP)-expressing neurons. In a recent article, Zhang et al. demonstrated that either diet- or genetically induced obesity promoted iron accumulation specifically in AgRP neurons. Preventing iron overload in AgRP neurons mitigated diet-induced obesity and related comorbidities in male mice.
Asunto(s)
Proteína Relacionada con Agouti , Hierro , Obesidad , Obesidad/metabolismo , Animales , Humanos , Hierro/metabolismo , Proteína Relacionada con Agouti/metabolismo , Ratones , Neuronas/metabolismo , Masculino , Hipotálamo/metabolismo , Sobrecarga de Hierro/metabolismoRESUMEN
Brain iron accumulation constitutes a pathognomonic indicator in several neurodegenerative disorders. Metal accumulation associated with dopaminergic neuronal death has been documented in Parkinson's disease. Through the use of in vivo and in vitro models, we demonstrated that lipid dysregulation manifests as a neuronal and glial response during iron overload. In this study, we show that cholesterol content and triacylglycerol (TAG) hydrolysis were strongly elevated in mice midbrain. Lipid cacostasis was concomitant with the loss of dopaminergic neurons, astrogliosis and elevated expression of α-synuclein. Exacerbated lipid peroxidation and markers of ferroptosis were evident in the midbrain from mice challenged with iron overload. An imbalance in the activity of lipolytic and acylation enzymes was identified, favoring neutral lipid hydrolysis, and consequently reducing TAG and cholesteryl ester levels. Notably, these observed alterations were accompanied by motor impairment in iron-treated mice. In addition, neuronal and glial cultures along with their secretomes were used to gain further insight into the mechanism underlying TAG hydrolysis and cholesterol accumulation as cellular responses to iron accumulation. We demonstrated that TAG hydrolysis in neurons is triggered by astrocyte secretomes. Moreover, we found that the ferroptosis inhibitor, ferrostatin-1, effectively prevents cholesterol accumulation both in neurons and astrocytes. Taken together, these results indicate that lipid disturbances occur in iron-overloaded mice as a consequence of iron-induced oxidative stress and depend on neuron-glia crosstalk. Our findings suggest that developing therapies aimed at restoring lipid homeostasis may lead to specific treatment for neurodegeneration associated with ferroptosis and brain iron accumulation.
Asunto(s)
Ferroptosis , Sobrecarga de Hierro , Trastornos Motores , Ratones , Animales , Metabolismo de los Lípidos , Trastornos Motores/metabolismo , Hierro/metabolismo , Peroxidación de Lípido , Neuronas Dopaminérgicas/metabolismo , Colesterol/metabolismo , LípidosRESUMEN
PURPOSE: The present study aimed at evaluating possible synergistic effects between two risk factors for cognitive decline and neurodegenerative disorders, i.e. iron overload and exposure to a hypercaloric/hyperlipidic diet, on cognition, insulin resistance, and hippocampal GLUT1, GLUT3, Insr mRNA expression, and AKT phosporylation. METHODS: Male Wistar rats were treated with iron (30 mg/kg carbonyl iron) or vehicle (5% sorbitol in water) from 12 to 14th post-natal days. Iron-treated rats received a standard laboratory diet or a high fat diet from weaning to adulthood (9 months of age). Recognition and emotional memory, peripheral blood glucose and insulin levels were evaluated. Glucose transporters (GLUT 1 and GLUT3) and insulin signaling were analyzed in the hippocampus of rats. RESULTS: Both iron overload and exposure to a high fat diet induced memory deficits. Remarkably, the association of iron with the high fat diet induced more severe cognitive deficits. Iron overload in the neonatal period induced higher insulin levels associated with significantly higher HOMA-IR, an index of insulin resistance. Long-term exposure to a high fat diet resulted in higher fasting glucose levels. Iron treatment induced changes in Insr and GLUT1 expression in the hippocampus. At the level of intracellular signaling, both iron treatment and the high fat diet decreased AKT phosphorylation. CONCLUSION: The combination of iron overload with exposure to a high fat diet only led to synergistic deleterious effect on emotional memory, while the effects induced by iron and by the high fat diet on AKT phosphorylation were comparable. These findings indicate that there is, at least to some extent, an additive effect of iron combined with the diet. Further studies investigating the mechanisms associated to deleterious effects on cognition and susceptibility for the development of age-associated neurodegenerative disorders are warranted.
Asunto(s)
Animales Recién Nacidos , Dieta Alta en Grasa , Transportador de Glucosa de Tipo 1 , Hipocampo , Resistencia a la Insulina , Sobrecarga de Hierro , Trastornos de la Memoria , Ratas Wistar , Animales , Masculino , Dieta Alta en Grasa/efectos adversos , Sobrecarga de Hierro/complicaciones , Sobrecarga de Hierro/metabolismo , Trastornos de la Memoria/etiología , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Ratas , Transportador de Glucosa de Tipo 1/metabolismo , Transportador de Glucosa de Tipo 1/genética , Transportador de Glucosa de Tipo 3/metabolismo , Transportador de Glucosa de Tipo 3/genética , Receptor de Insulina/metabolismo , Receptor de Insulina/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Glucemia/metabolismo , Insulina/sangre , Transducción de SeñalRESUMEN
Background: Iron overload is frequent in patients with chronic liver disease, associated with shorter survival after liver transplantation in patients with hereditary hemochromatosis. Its effect on patients without hereditary hemochromatosis is unclear. The aim of the study was to study the clinical impact of iron overload in patients who underwent liver transplantation at an academic tertiary referral center. Methods: We performed a retrospective cohort study including all patients without hereditary hemochromatosis who underwent liver transplantation from 2015 to 2017 at an academic tertiary referral center in Mexico City. Explant liver biopsies were reprocessed to obtain the histochemical hepatic iron index, considering a score ≥ 0.15 as iron overload. Baseline characteristics were compared between patients with and without iron overload. Survival was estimated using the Kaplan-Meier method, compared with the log-rank test and the Cox proportional hazards model. Results: Of 105 patients included, 45% had iron overload. Viral and metabolic etiologies, alcohol consumption, and obesity were more frequent in patients with iron overload than in those without iron overload (43% vs. 21%, 32% vs. 22%, p = 0.011; 34% vs. 9%, p = 0.001; and 32% vs. 12%, p = 0.013, respectively). Eight patients died within 90 days after liver transplantation (one with iron overload). Complication rate was higher in patients with iron overload versus those without iron overload (223 vs. 93 events/100 personmonths; median time to any complication of 2 vs. 3 days, p = 0.043), without differences in complication type. Fatality rate was lower in patients with iron overload versus those without iron overload (0.7 vs. 4.5 deaths/100 person-months, p = 0.055). Conclusion: Detecting iron overload might identify patients at risk of early complications after liver transplantation. Further studies are required to understand the role of iron overload in survival.
Asunto(s)
Hemocromatosis , Sobrecarga de Hierro , Hepatopatías , Trasplante de Hígado , Humanos , Trasplante de Hígado/efectos adversos , Hemocromatosis/complicaciones , Hemocromatosis/epidemiología , Hemocromatosis/patología , Estudios Retrospectivos , Sobrecarga de Hierro/etiología , Sobrecarga de Hierro/complicaciones , Hepatopatías/complicaciones , Hepatopatías/metabolismo , Hepatopatías/patología , Hígado/metabolismoRESUMEN
Iron overload, characterized by accumulation of iron in tissues, induces a multiorgan toxicity whose mechanisms are not fully understood. Using cultured cell lines, Caenorhabditis elegans, and mice, we found that ferroptosis occurs in the context of iron-overload-mediated damage. Exogenous oleic acid protected against iron-overload-toxicity in cell culture and Caenorhabditis elegans by suppressing ferroptosis. In mice, oleic acid protected against FAC-induced liver lipid peroxidation and damage. Oleic acid changed the cellular lipid composition, characterized by decreased levels of polyunsaturated fatty acyl phospholipids and decreased levels of ether-linked phospholipids. The protective effect of oleic acid in cells was attenuated by GW6471 (PPAR-α antagonist), as well as in Caenorhabditis elegans lacking the nuclear hormone receptor NHR-49 (a PPAR-α functional homologue). These results highlight ferroptosis as a driver of iron-overload-mediated damage, which is inhibited by oleic acid. This monounsaturated fatty acid represents a potential therapeutic approach to mitigating organ damage in iron overload individuals.
Asunto(s)
Ferroptosis , Sobrecarga de Hierro , Animales , Ratones , Caenorhabditis elegans , Ácido Oléico/farmacología , Receptores Activados del Proliferador del Peroxisoma , Sobrecarga de Hierro/tratamiento farmacológico , Hierro , Éteres FosfolípidosRESUMEN
La hemocromatosis es una enfermedad caracterizada por el excesivo depósito de hierro en múltiples órganos, entre ellos hígado, páncreas, piel y corazón. La infiltración de este último es un importante factor en morbilidad y mortalidad. Presentamos un caso de un paciente pediátrico con insuficiencia cardíaca terminal que ameritó trasplante cardíaco, que resultó sin complicaciones. Posterior a la cirugía, mostró mejoría bioquímica y clínica, lo que influyó positivamente en su calidad de vida y prolongó su supervivencia.
Hemochromatosis is a disease characterized by excess iron stores in multiple organs, including the liver, pancreas, skin, and heart. The infiltration of the heart is an important factor in morbidity and mortality. Here we describe the case of a pediatric patient with end-stage heart failure who required a heart transplantation, with no complications. After the surgery, she showed biochemical and clinical improvement, with a positive impact on her quality of life and a prolonged survival.
Asunto(s)
Humanos , Femenino , Niño , Trasplante de Corazón , Sobrecarga de Hierro/complicaciones , Hemocromatosis/complicaciones , Hemocromatosis/diagnóstico , Calidad de Vida , HígadoRESUMEN
ABSTRACT Introduction: During pregnancy, the iron requirement increases to meet the optimal growth of the fetus and prevent iron deficiency anemia-related complications in the mother. However, in sickle cell disease (SCD) primarily due to repeated blood transfusions and hemolysis-induced recycling of iron, its supplementation during pregnancy remains questionable and may be harmful. Methods: Twenty-five pregnant women with homozygous SCD and 25 pregnant women with normal hemoglobin variants were included as cases and control, respectively. Pregnancy and sickle cell anemia (SCA) were diagnosed using standard protocols. The serum iron, serum ferritin, total iron-binding capacity (TIBC), percentage transferrin saturation and C-reactive protein were estimated, as per the manufacturer's protocol. The complete blood count was performed. The unpaired 't-test' was performed using the SPSS v23.0 and the principal component analysis (PCA) was performed using the online software MetaboAnalyst for statistical analysis. Main Results: The studied cases had significantly lower mean hemoglobin and higher mean corpuscular volume (MCV), compared to controls. The mean serum-iron, serum-ferritin and percentage transferrin-saturation in the cases were significantly higher than that of the controls, while the TIBC was lower in the cases (p < 0.0001). The mean level of serum iron, ferritin, percentage transferrin saturation and TIBC were 309.44 ± 122.40mcg/dl, 860.36 ± 624.64ng/ml, 42.6 ± 17.30% and 241.32 ± 96.30 mcg/dl, respectively, in the cases and 95.36 ± 41.90mcg/dl, 122.28 ± 49.70ng/ml, 15.83 ± 3.10% and 492.6 ± 149.40mcg/dl in the controls, respectively. Higher MCV, mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) with lower hemoglobin (Hb) were noted in the cases. The PCA revealed that the cases were more heterogeneous in terms of the variability of the iron status and hematological indices than the controls. Conclusion: The current study shows iron sufficiency in most cases of pregnancy with SCA and suggests that evaluation of iron status must be made before initiating iron prophylaxis in pregnant women with SCA, especially in regions having a high prevalence of sickle cell hemoglobinopathy.
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Humanos , Embarazo , Embarazo , Anemia de Células Falciformes , Sobrecarga de Hierro , Fármacos HematológicosRESUMEN
In recent years, it has been identified that excess iron contributes to the development of various pathologies and their complications. Kidney diseases do not escape the toxic effects of iron, and ferroptosis is identified as a pathophysiological mechanism that could be a therapeutic target to avoid damage or progression of kidney disease. Ferroptosis is cell death associated with iron-dependent oxidative stress. To study the effects of iron overload (IOL) in the kidney, numerous animal models have been developed. The methodological differences between these models should reflect the IOL-generating mechanisms associated with human IOL diseases. A careful choice of animal model should be considered for translational purposes.
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Ferroptosis , Sobrecarga de Hierro , Animales , Humanos , Riñón , Hierro , Modelos AnimalesRESUMEN
The indiscriminate use of oral ferrous sulfate (FeSO4) doses induces significant oxidative damage to health. However, carotene-rich foods such as buriti oil can help the endogenous antioxidant defense and still maintain other body functions. This study aimed to assess the effects of buriti oil intake in iron-overloaded rats by FeSO4 administration. Buriti oil has ß-carotene (787.05 mg/kg), α-tocopherol (689.02 mg/kg), and a predominance of monounsaturated fatty acids (91.30 g/100 g). Wistar rats (n = 32) were subdivided into two control groups that were fed a diet containing either soybean or buriti oil; and two groups which received a high daily oral dose of FeSO4 (60 mg/kg body weight) and fed a diet containing either soybean (SFe) or buriti oil (Bfe). The somatic and hematological parameters, serum lipids, superoxide dismutase (SOD), and glutathione peroxidase (GPx) were determined after 17 days of iron overload. Somatic parameters were similar among groups. BFe showed a decrease in low-density lipoprotein (38.43%) and hemoglobin (7.51%); an increase in monocytes (50.98%), SOD activity in serum (87.16%), and liver (645.50%) hepatic GPx (1017.82%); and maintained serum GPx compared to SFe. Buriti oil showed systemic and hepatic antioxidant protection in iron-overloaded rats, which may be related to its high carotenoid, tocopherol, and fatty acid profile.
Asunto(s)
Antioxidantes , Sobrecarga de Hierro , Ratas , Animales , Antioxidantes/farmacología , Ratas Wistar , Aceites de Plantas/farmacología , Carotenoides/farmacología , Hierro/farmacología , Superóxido Dismutasa/farmacología , HígadoRESUMEN
Abstract Introduction Magnetic resonance imaging (MRI) T2* technique is used to assess iron overload in the heart, liver and pancreas of thalassaemic patients. Optimal iron chelation and expected tissue iron response rates remain under investigation. The objective of this study was to analyse serum ferritin and the iron concentration in the heart, liver and pancreas measured by MRI T2*/R2* during regular chelation therapy in a real-world cohort of patients with thalassemia. Methods We evaluated thalassaemic patients ≥ 7 years old undergoing chelation/transfusion therapy by MRI and assessed serum ferritin at baseline and follow-up from 2004-2011. Results We evaluated 136 patients, 92% major thalassaemic, with a median age of 18 years, and median baseline ferritin 2.033ng/ml (range: 59-14,123). Iron overload distribution was: liver (99%), pancreas (74%) and heart (36%). After a median of 1.2 years of follow-up, the iron overload in the myocardium reduced from 2,63 Fe mg/g to 2,05 (p 0.003). The optimal R2* pancreas cut-off was 148 Hertz, achieving 78% sensitivity and 73% specificity. However, when combining the R2* pancreas cut off ≤ 50 Hertz and a ferritin ≤ 1222 ng/ml, we could reach a negative predictive value (NPV) of 98% for cardiac siderosis. Only 28% were undergoing combined chelation at baseline assessment, which increased up to 50% on follow up evaluation. Conclusions Chelation therapy significantly reduced cardiac siderosis in thalassaemic patients. In patients with moderate/severe liver iron concentration undergoing chelation therapy, ferritin levels and myocardium iron improved earlier than the liver siderosis.
Asunto(s)
Humanos , Niño , Talasemia , Sobrecarga de Hierro , Terapia por QuelaciónRESUMEN
Hemochromatosis is a disease characterized by excess iron stores in multiple organs, including the liver, pancreas, skin, and heart. The infiltration of the heart is an important factor in morbidity and mortality. Here we describe the case of a pediatric patient with end-stage heart failure who required a heart transplantation, with no complications. After the surgery, she showed biochemical and clinical improvement, with a positive impact on her quality of life and a prolonged survival.
La hemocromatosis es una enfermedad caracterizada por el excesivo depósito de hierro en múltiples órganos, entre ellos hígado, páncreas, piel y corazón. La infiltración de este último es un importante factor en morbilidad y mortalidad. Presentamos un caso de un paciente pediátrico con insuficiencia cardíaca terminal que ameritó trasplante cardíaco, que resultó sin complicaciones. Posterior a la cirugía, mostró mejoría bioquímica y clínica, lo que influyó positivamente en su calidad de vida y prolongó su supervivencia.
Asunto(s)
Trasplante de Corazón , Hemocromatosis , Sobrecarga de Hierro , Humanos , Femenino , Niño , Hemocromatosis/complicaciones , Hemocromatosis/diagnóstico , Calidad de Vida , Sobrecarga de Hierro/complicaciones , HígadoRESUMEN
Iron deficiency is the leading cause of anaemia. In Argentina, the prevalence of anaemia and iron deficiency is very high; for that reason, the Argentine Society of Pediatrics recommends daily ferrous sulphate supplementation as a preventive treatment strategy. Alternatively, weekly ferrous sulphate supplementation has also been shown to be effective for anaemia prevention. Excess iron could be related to oxidative stress, which may in turn cause cytomolecular damage. Both can be prevented with vitamin E supplementation. We evaluated the effect of both daily and weekly ferrous sulphate supplementation combined with two doses of vitamin E on cell viability, oxidative stress and cytomolecular damage in peripheral blood cultured in vitro. The experimental design included the following groups: untreated negative control, two vitamin E controls (8·3 and 16·6 µg/ml), weekly ferrous sulphate supplementation (0·55 mg/ml) with each vitamin E dose, daily ferrous sulphate supplementation (0·14 mg/ml) with each vitamin E dose and a positive control. Daily ferrous sulphate supplementation decreased cell viability and increased the levels of reactive oxygen species, lipid peroxidation and cytomolecular damage (P < 0·5) compared with the weekly supplementation, probably due to the excess iron observed in the former. Vitamin E seemed to reduce ferrous sulphate-induced oxidative stress and genomic damage.
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Anemia Ferropénica , Anemia , Deficiencias de Hierro , Sobrecarga de Hierro , Humanos , Niño , Vitamina E/farmacología , Vitamina E/uso terapéutico , Suplementos Dietéticos , Compuestos Ferrosos/farmacología , Compuestos Ferrosos/uso terapéutico , Hierro , Genómica , Modelos TeóricosRESUMEN
Introducción. El objetivo de esta investigación fue comparar el perfil bioquímico y clínico de los pacientes con hiperferritinemia secundaria a hemocromatosis hereditaria (HH), frente a aquellos con hiperferritinemia por causas sospechosas de sobrecarga de hierro (Fe) diferentes a la HH. Metodología. Se estudiaron 92 pacientes (61 hombres y 31 mujeres), remitidos tras la detección de valores de ferritina >300 µg/L en hombres y >200 µg/L en mujeres. En todos se analizaron datos demográficos generales, comorbilidades, motivo de remisión para estudios de hiperferritinemia, manifestaciones clínicas, antecedente familiar de HH y tratamiento reci-bido. Los resultados de las pruebas de laboratorio, imagenología, hallazgos histopatológicos y estudios genéticos, se describieron según la disponibilidad. Resultados. El 96,74 % de los pacientes fueron evaluados en consulta externa, 86,96 % procedían de Medellín o de otros municipios de Antioquia, Colombia. La edad promedio de los participantes fue de 52 años, la principal razón para ser derivados para estudios fue la elevación de los marcadores de Fe sérico, la causa más frecuente de hiperferritinemia fueron los diagnósticos diferentes a la HH (64,13 %) y entre quienes no tenían HH, la etiología metabólica fue la más común (59,32 %). Los pacientes con HH tuvieron niveles más elevados de ferritina y Fe sérico, mientras que en el grupo sin HH se presentaron mayores elevaciones en la saturación de transferrina, transfe-rrina y transaminasas. En pacientes con sobrecarga de Fe, la mutación más frecuentemente encontrada fue la homocigota H63D (36,67 %). Finalmente, 93,94 % de los pacientes con HH recibieron tratamiento con flebotomías, mientras que los cambios en el estilo de vida fueron indicados en el 55,93 % de los pacientes sin HH. Conclusiones. La hiperferritinemia es una presentación clínica frecuente y es importante hacer un abordaje sistemático para identificar sus causas. Aunque la HH es una causa importante de elevación persistente de ferritina, en el enfoque de los pacientes con esta condición, se deben descartar etiologías más frecuentes como la hiperferritinemia de etiología metabólica.
Introduction. The aim of this investigation was to compare the biochemical and clinical profile of patients with secondary hyperferritinemia caused by hereditary hemochromatosis (HH), versus those with hyperferritinemia due to suspected causes of iron (Fe) overload other than HH. Methodology. A total of 92 patients (61 men and 31 women) referred after the detection of ferritin values >300 µg/L in men and >200 µg/L in women were studied. General demographic data, comorbidities, referral reasons for hyperferritinemia studies, clinical manifestations, family history of HH, and treatment received were analyzed in all patients. The results of laboratory tests, medical imaging, histopatho-logical findings, and genetic studies were described based on availability. Results. Of all patients, 96.74% were evaluated as outpatients, 86,96% from the municipality of Medellin in Antioquia, Colombia. The average age of the participants was 52 years, the main reason for being referred for studies was the elevation of serum Fe markers, the most frequent cause of hyperferritinemia in the population studied were conditions other than HH (64.13%), and among those who did not have HH, the metabolic etiology was the most common cause (60%). Patients with HH had higher levels of ferritin and serum Fe, while in the group without HH there were greater elevations of transferrin saturation, transferrin and transaminases. In patients with iron overload, the most frequently found mutation was the homozygous H63D (36.67%). Finally, 93.94% of the patients with HH received phlebotomy treatment, while changes in lifestyle were indicated in 55.93% of patients without HH. Conclusions. Hyperferritinemia is a frequent clinical presentation and it is important to make a systematic approach to identify its causes. Although HH is an important cause of persistent ferritin elevation, in the approach to patients with this condition, more frequent etiologies such as hyperfe-rritinemia of metabolic etiology should be ruled out.
Asunto(s)
Humanos , Hiperferritinemia , Hemocromatosis , Flebotomía , Sobrecarga de Hierro , Ferritinas , TransaminasasRESUMEN
La hemocromatosis es un desorden en el cual la sobrecarga progresiva de hierro puede llevar a complicaciones sistémicas con gran morbimortalidad. Es una entidad clinicopatológica, con múltiples genes comprometidos y una fisiopatología común, con una expresión clínica y fenotípica variable, que depende de múltiples factores, tanto individuales como ambientales. Para su diagnóstico y seguimiento adecuado es necesario tener en cuenta elementos clínicos, bioquímicos y moleculares. En esta revisión, se presentan las generalidades de la hemocromatosis, además de sus mecanismos fisiopatológicos y moleculares, teniendo en cuenta su valor para el diagnóstico de la enfermedad. Adicionalmente, se describe la clasificación y un algoritmo diagnóstico propuestos recientemente por grupos de trabajo de expertos, así como las opciones de manejo y seguimiento de los pacientes con hemocromatosis
Hemochromatosis is a disorder in which progressive iron overload may lead to systemic complications with potential morbidity and mortality. It is a clinicopathologic entity that involves multiple genes and common pathophysiology, and has a variable clinical and phenotypic expression that depends on several individual and environmental factors. To make the diagnosis and perform a proper follow-up, clinical, biochemical, and molecular elements must be considered. This review aims to present the general characteristics of hemochromatosis, its molecular and pathophysiologic mechanisms, and their significance in the diagnosis of this disorder. In addition, a new classification and a proposed diagnostic algorithm by an expert working group are described, as well as management and follow-up options for patients with hemochromatosis
Asunto(s)
Humanos , Hemocromatosis , Flebotomía , Sobrecarga de Hierro , Ferritinas , Proteína de la Hemocromatosis , Cirrosis HepáticaRESUMEN
Iron overload (IOL) increases the risk of diabetes mellitus (DM). Capsaicin (CAP), an agonist of transient receptor potential vanilloid-1 (TRPV1), reduces the effects of IOL. We evaluated the effects of chronic CAP administration on hepcidin expression, kidney iron deposits, and urinary biomarkers in a male Wistar rat model with IOL and DM (DM-IOL). IOL was induced with oral administration of iron for 12 weeks and DM was induced with streptozotocin. Four groups were studied: Healthy, DM, DM-IOL, and DM-IOL + CAP (1 mg·kg-1·day-1 for 12 weeks). Iron deposits were visualized with Perls tissue staining and a colorimetric assay. Serum hepcidin levels were measured with an enzyme-linked immunosorbent assay. Kidney biomarkers were assayed in 24 h urine samples. In the DM-IOL + CAP group, the total area of iron deposits and the total iron content in kidneys were smaller than those observed in both untreated DM groups. CAP administration significantly increased hepcidin levels in the DM-IOL group. Urinary levels of albumin, cystatin C, and beta-2-microglobulin were similar in all three experimental groups. In conclusion, we showed that in a DM-IOL animal model, CAP reduced renal iron deposits and increased the level of circulating hepcidin.
Asunto(s)
Diabetes Mellitus Experimental , Sobrecarga de Hierro , Ratas , Masculino , Animales , Hepcidinas/metabolismo , Hierro/metabolismo , Capsaicina/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Ratas Wistar , Sobrecarga de Hierro/complicaciones , Sobrecarga de Hierro/tratamiento farmacológico , Sobrecarga de Hierro/metabolismo , Riñón/metabolismo , BiomarcadoresRESUMEN
The enzyme heme oxygenase-1 (HO-1) has cytoprotective effects by catalyzing the degradation of heme to produce carbon monoxide, iron and biliverdin. Furthermore, HO-1 activity has been associated with successful pregnancy. On the other hand, in the context of certain inflammatory conditions, HO-1 can induce iron overload and cell death. To investigate the role of HO-1 in gestational malaria, pregnant BALB/c mice were infected with Plasmodium berghei ANKA in early, mid and late gestation. We found that malaria affected the pregnancy outcome in the three periods evaluated. However, only poor pregnancy outcomes in early pregnancy were related to HO-1 upregulation, iron overload, lipid peroxidation and necrosis of the decidua, which were prevented by HO-1 inhibition. In conclusion, HO-1 expression must be finely tuned in gestational malaria to avoid the deleterious effect of increased enzyme activity.
Asunto(s)
Hemo-Oxigenasa 1 , Malaria , Resultado del Embarazo , Protoporfirinas , Animales , Femenino , Hemo-Oxigenasa 1/antagonistas & inhibidores , Hemo-Oxigenasa 1/metabolismo , Sobrecarga de Hierro , Peroxidación de Lípido , Malaria/tratamiento farmacológico , Ratones , Plasmodium berghei , Embarazo , Complicaciones Parasitarias del Embarazo/tratamiento farmacológico , Protoporfirinas/farmacologíaRESUMEN
BACKGROUND: Excess bodily iron content is commonly associated with obesity and metabolic associated medical conditions and is thought to lead to cardiovascular disease. The effect of Roux-en-Y gastric bypass (RYGB) on hepatic iron overload remains to be determined. OBJECTIVE: To assess the evolution of histologically proven hepatic iron overload after RYGB. METHODS: This is an exploratory historical cohort study in which 42 individuals who underwent RYGB, and then a second surgical procedure had paired liver biopsies collected. Hepatic iron overload and NAFLD features were assessed through histopathological examination. Biochemical iron metabolism parameters were also assessed. RESULTS: The mean age at RYGB was 47 ± 10.2 years and 92.9% were female. The average time elapsed between RYGB and the second surgical procedure was 20.6 ± 15.4 months. The mean percentage of total weight loss between the two procedures was 26.7 ± 9.4%. Significant reductions in ferritin (220.8 ± 202.9 vs. 101.6 ± 116.7 ng/mL; p = 0.006), hemoglobin (13.7 ± 1.8 vs. 12.1 ± 2.6 g/dL; p = 0.01), and red blood cell count (4.7 ± 0.7 vs. 4.3 ± 0.5 106/mm3; p = 0.003) were observed, as well as reductions in the frequencies of steatosis (83.3% vs. 23.8%; p < 0.0001) and steatohepatitis (52.4% vs. 11.9%; p < 0.0001). The frequency of hepatic iron overload significantly decreased from 16.7 to 2.4% (p = 0.03). CONCLUSION: RYGB led to a significant decrease in hepatic iron overload, emerging as a possible therapeutical tool for this condition in individuals with obesity and dysmetabolic iron overload syndrome.