Neuroprotective effects of sinapic acid involve the iron regulatory role on the rotenone-induced Parkinson's disease model

Abstract In the last decades, ferroptosis and its relationship with Parkinson's disease have gained significant attention. Compounds that affect ferroptosis and iron-dependent pathways in particular, have possible candidates for study in this context.Sinapic acid is an iron-chelator and high antioxidant bioactive phenolic acid. Its neuroprotective action, due to the antioxidant capacity, has been shown in several experimental models.However, the relationship between iron and antioxidant actions is still misunderstood and therefore, in the current study, we tried to investigate the effects of sinapic acid in rotenone-induced Parkinson's disease with the aspect of ferroptosis and iron-dependent alterations.The Parkinson's disease model was induced by a single dose intrastriatal and intrategmental rotenone (5µg/µl) injection.Sinapic acid (30mg/ kg) was orally administered during a 28-day period after the Parkinson's disease model was validated.Our results demonstrated that sinapic acid treatment attenuated rotenone-induced increase of serum transferrin and iron levels.Furthermore, sinapic acid inhibited rotenone-induced heme oxygenase-1(HO-1) increase and decrease of glutathione peroxidase-4 (GPx-4) levels in brain tissue. Also, sinapic acid treatment decreased motor impairment, likely as a result of the ameliorative effects on the tyrosine hydroxylase immunoreactivity loss after the rotenone insult.Our study suggests that the iron regulatory role of sinapic acid possibly plays a role in the protective effect on rotenone-induced neuronal damage.

Functional iron deficiency in patients on hemodialysis: prevalence, nutritional assessment, and biomarkers of oxidative stress and inflammation / Deficiência funcional de ferro em pacientes em hemodiálise: prevalência, avaliação nutricional e de biomarcadores de estresse oxidativo e de inflamação

Abstract Introduction: Anemic patients with chronic kidney disease (CKD) can be divided into anemic patients without or with functional iron deficiency (FID). The increase in the number of cases of hemosiderosis in patients on hemodialysis (HD) attributed to excessive intravenous iron replacement has called for the investigation of the factors involved in the genesis of FID. Objectives: This study aimed to describe the prevalence of FID in patients with CKD on HD, characterize the included individuals in terms of clinical and workup parameters, and assess their nutritional, oxidative stress, and inflammation statuses. This cross-sectional study assembled a convenience sample of 183 patients with CKD on HD treated in Southern Brazil. Patients meeting the inclusion and exclusion criteria were divided into two groups, one with anemic subjects with FID and one with anemic patients without FID. Participants answered a questionnaire probing into socio-epidemiological factors, underwent anthropometric measurements, and were tested for markers of anemia, oxidative stress, inflammation, and nutrition. Statistical analysis: The date sets were treated on software package GraphPad InStat version 3.1. Variables were tested with the Kolmogorov-Smirnov, chi-square, Student's t, and Mann-Whitney tests. Statistical significance was attributed to differences with a p < 0.05. Results: Markers of inflammation were not statistically different between the two groups. Markers of anemia and nutrition were significantly lower in patients with FID. Patients with FID were prescribed higher doses of parenteral iron (p < 0,05). Discussion: FID was associated with lower nutritional marker levels, but not to increased levels of markers of inflammation or oxidative stress, as reported in the literature. Additional studies on the subject are needed.

Resumo Introdução: A anemia na DRC pode ser dividida em anemia sem deficiência funcional de ferro e com deficiência funcional de ferro (ADFF). Diante do aumento dos casos de hemossiderose em pacientes em hemodiálise, atribuídos à reposição excessiva de ferro endovenoso, maiores conhecimentos sobre os fatores envolvidos na gênese da ADFF são importantes. Objetivos: documentar a prevalência de ADFF em renais crônicos em hemodiálise. Caracterizar clínica e laboratorialmente os portadores de ADFF em HD e avaliar o estado nutricional, estresse oxidativo e inflamatório. Estudo transversal, amostra de conveniência, envolvendo 183 renais crônicos em hemodiálise no sul do Brasil. Após aplicação dos critérios de exclusão, os pacientes foram separados em dois grupos: portadores de anemia com e sem deficiência funcional de ferro. Foram submetidos a questionário socioepidemiológico, à análise antropométrica e análise laboratorial dos marcadores de anemia, estresse oxidativo, inflamatórios e nutricionais. Análise estatística: programa GraphPad InStat versão 3.1. Foram aplicados os testes: Kolmogorov-Smirnov, qui-quadrado, t de Student e Mann-Whitney. Nível de significância adotado de 5%. Resultados: não houve diferença significativa nos marcadores inflamatórios entre os dois grupos. Houve diferença significativa nos marcadores de anemia e nutrição, significativamente menores nos pacientes com ADFF. Pacientes com ADFF receberam doses mais elevadas de ferro parenteral (p < 0,05). Discussão: ADFF esteve associada a menores valores de marcadores nutricionais, mas não esteve associada a marcadores inflamatórios ou de estresse oxidativo aumentados, como relatado na literatura. Estudos adicionais sobre o tema são necessários.

Prospecção de sideróforos do tipo hidroxamato e quinona para terapia de sobrecarga de ferro / Prospection of hydroxamate and quinone-type siderophores for iron overload chelation therapy

A sobrecarga de ferro é uma condição prejudicial para os pacientes, que apresentam uma diminuição significativa na qualidade de vida. Os fármacos quelantes são moléculas que têm capacidade de uso clínico para atuar como atenuadores da sobrecarga de metais. Neste trabalho apresentamos uma análise de sideróforos do tipo hidroxamato e quinona, com o objetivo de ampliar a gama de terapia de sobrecarga de ferro. Para cada composto foi realizado um ensaio competitivo com a sonda calce- ína para verificar a capacidade de ligação do ferro, e um ensaio antioxidante baseado na supressão da oxidação dependente de ferro da dihidrorrodamina (DHR) sob ascorbato. Foi observado que o hidroxamato cíclico piridoxatina apresentou capacidade de sequestrar ferro de substratos de alta afinidade, tanto em meio tamponado quanto em meio intracelular. Em ambas as situações também se mostrou um antioxidante eficiente. Entretanto, parece ser o mais tóxico do grupo dos hidroxamatos (que ainda continha o hidroxamato linear desferricoprogênio e o aromático desferriastercromo). Outros compostos naturais também foram estudados como possíveis candidatos a fármacos para sobrecarga de ferro. Complexos de ferro foram caracterizados por espectrofotometria para avaliar a estequiometria possível, considerando os sítios de ligação para cada composto. Ensaios de fluorescência revelaram que entre os quatro compostos em estudo (ácido clorogênico, lapachol, hemateína e hematoxilina), o complexo entre ferro e hemateína apresenta maior estabilidade relativa do que outros

Iron overload is a harmful condition for patients, who have a significant decrease in life quality. Chelating drugs are molecules that have the capacity for clinical use to act as attenuators of metal overload. In this work we present an analysis of hydroxamate and quinone-type siderophores, intending to broaden the range of iron overload therapy. For each compound it was conducted a competitive assay with the fluorescent probe calcein to verify the iron binding ability, and an antioxidant assay based on suppression of the iron-dependent oxidation of dihydrorhodamine (DHR) under ascorbate. It was observed that cyclic hydroxamate pyridoxatin displayed good ability to scavenge iron from high affinity substrates both in buffer and in intracellular medium. It was also an efficient antioxidant in both setups. However, pyridoxatin seems to be the most toxic from the hydroxamate group (composed also by the linear desferricoprogen and the aromatic desferriasterchrome). Other natural compounds have also been studied as possible candidates for iron-overload drug therapy. Iron complexes were characterized by spectrophotometry to assess the possible stoichiometry considering the binding sites for each compound. Fluorescence assays revealed that among the four compounds in study (chlorogenic acid, lapachol, hematein and hematoxylin), the complex between iron and hematein has higher relative stability than others

Hierro excesivo y cardiopatía coronaria énfasis en la generación de diabetes y muerte súbita / Excessive iron and coronary cardiopathy emphasis in the generation of diabetes and sudden death

El Hierro es esencial para la vida, pero su exceso libre o acumulado es un tóxico celular, puesto que es el metal que menos se elimina en el humano. Es un potente creador de radicales libres que genera/incrementa significativamente el estrés oxidativo. El hierro influencia el metabolismo de la glucosa, inclusive en ausencia de sobrecargas elevadas; incrementa el daño cardiovascular pre- existente, y su reducción alivia la patología cardiaca coronaria y reducir o prevenir sus complicaciones. Ciertamente, elevados niveles de hierro catalítico y/o acumulado como ferritina aumenta el riesgo para el desarrollo de aterosclerosis coronaria. El hierro libre cataliza la peroxidación lipídica; al igual que las mayores reservas corporales de hierro aceleraría la disfunción endotelial en la patología isquémica aguda: el exceso del hierro genera una injuria vascular oxidativa /inflamatoria /protrombótica vascular e insulinoresistencia. En la población general, las reservas corporales férricas se asocian estrechamente con el desarrollo de intolerancia glucídica, diabetes tipo 2 y gestacional; y aumenta silenciosamente las complicaciones del sujeto dislipidémico, hipertenso, y diabético. Se ha demostrado que la donación /extracción de sangre por flebotomía reduce significativamente la incidencia y gravedad de los eventos coronaríos: la isquemia por reperfusión, y procedimientos como la angioplastia coronaria transluminal transluminal percutánea y el bypass coronario (Holsworth, 2013). La donación frecuente de sangre conduce a una reducción de las reservas de hierro y disminuye el exceso de insulina (basal y post-prandíal), mejorando la sensibilidad insulínica encontroles sanos; y los parámetros hemodinámicos - metabólicos en sujetos hipertensos y diabéticos...

Iron is essential for life, but excess iron can be toxic. As a potent free radical creator, iron generates hydroxyl radicals leading to significant oxidative stress. Iron overload has been suggested to increase the cardiovascular risk in the general population. Iron influences glucose metabolism, even in the absence of significant iron overload, and its reduction may alleviate coronary heart disease and reduced or prevent their complications. In fact, high stored or free iron levels (measured by serum ferritin or catalytic iron concentrations) elevate risk for development of coronary atherosclerosis. Increased body iron stores may accelerate endothelial dysfunction in acute ischemic syndromes. Then, excess body iron originates oxidative injury that is associated with systemic and vascular inflammation, phrothrombotic conditions and insulin resistance (Williams, 2002) In the general population, body iron stores are positively associated with the development of glucose intolerance, type 2 diabetes and gestational diabetes. Further, it has been demonstrated that blood donation significant drops in the incidence of cardiovascular events, as well as in procedures such as percutaneous transluminal coronary angioplasty and coronary artery bypass grafting (Holsworth, 2013). Accordingly, frequent blood donations decreased iron stores in healthy volunteers, improving insulin sensitivity and hemodynamic parameters. This sample therapy constitutes a protective factor for the development of type 2 diabetes, and the cardiac disorders insulin-resistance associated...

Protective effect of Clerodendrum colebrookianum leaves against iron-induced oxidative stress and hepatotoxicity in Swiss albino mice.

Liver toxicity due to iron overload leads to oxidative damage of proteins, lipids and nucleic acids which in turn manifests several human diseases. Here, we evaluated the improving effect of Clerodendrum colebrookianum leaf on iron overload induced liver injury along with in vitro iron chelation and the protection of Fenton reaction induced DNA damage was conducted. Iron overload was induced by intraperitoneal administration of iron-dextran into mice. Post oral administration of different doses of the extract (50, 100 and 200 mg/kg body weight) showed significant decrease in different biochemical markers such as liver iron, serum ferritin and serum enzyme levels, along with decreased lipid peroxidation, protein oxidation and collagen content. In addition, the extract effectively enhanced the antioxidant enzyme levels and also exhibited the potential activity of the reductive release of ferritin iron. The protective effect of C. colebrookianum extract on injured liver was furthermore supported by the histopathological studies that showed improvement histologically. In conclusion, the present results demonstrated the hepatoprotective efficiency of C. colebrookianum leaf in iron overloaded mice, and hence, a potential iron chelating drug for iron overload diseases.

Effects of iron chelating therapy and / or HBV-vaccination on beta-thalassemia major patients

Thalassemia is a genetic inherited blood disorder in which the body makes abnormal hemoglobin with excessive destruction of red blood cells, which leads to anemia. For many years, hepatitis B virus was a major problem for patients with thalassemia substantially contracted from blood transfusions. The development of effective vaccine has further reduced the magnitude of the problem of hepatitis B. Iron chelators are used to remove excess iron that accumulates due to repeated blood transfusion. To compare thalassemic patients either have or haven't HCV with healthy persons as regards biochemical indices taking in consideration effect of vaccination against HBV or not and using iron chelating therapy or not by the studied persons. A case control study in which 40 thalassemic, blood transfusion dependent patients were chosen randomly to act as a case group from thalassemic patients attending the VACSERA Company. The cases [40 patients] they were classified to patients having HCV, patients were HBV vaccinated, other non vaccinated, using iron chelating therapyor don't use it. Another 10 healthy and non thalassemic persons were chosen randomly among persons attending the same company as a control group to be matched with the case group. 50% of studied thalassemic patients had HCV seropositivity. Biochemical blood indices which were found to be significantly elevated among thalassemic patients than controls were ALT, AST, ALP, GGT and LDH enzymes in addition to serum iron, ferritin and globulin mostly in HBV non-vaccinated and iron chelating therapy non dependent patients while, other biochemical indices which were significantly decreased among thalassemic patients compared to controls included: total cholesterol, total protein, albumin and albumin/globulin ratio mostly in HBV vaccinated and iron chelating non dependent patients. This study illustrated the effectiveness of iron chelators agentsand the importance of vaccination for reduction of morbidity and mortality

Protective effects of lycopene on oxidative stress, proliferation and autophagy in iron supplementation rats

Lycopene is common in diet and known for its antioxidant activities. However, the impact of lycopene on iron metabolism is poorly investigated. In this study, we hypothesize that lycopene can prevent iron-mediated oxidative stress, proliferation and autophagy in liver and use a rat model of nutritional iron supplementation to confirm its intervention in these defence mechanisms. We found that iron supplementation induced cell proliferation predominantly in non parenchymal cells compared with hepatocytes, but not apoptosis. In addition, iron was accumulated within the hepatic lysosomes where it triggered autophagy as evidenced by the formation of autophagic vesicles detected by LC3-B staining. Iron supplementation also induced morphologic alterations of the mitochondrial membranes probably due to increased lipid peroxidation as indicated by elevated iron and malondialdehyde concentrations in serum and tissues. Lycopene reduced iron-catalyzed lipid peroxidation by decreasing the malondialdehyde level in the liver and colon and enhancing the total superoxide dismutase activities in serum and tissues. The result suggest that lycopene prevents iron-induced oxidative stress, proliferation and autophagy at both biochemical and histological levels due to its potent free radical scavenging and antioxidant properties.

Hepcidina: su interacción con la hemojuvelina y su aporte en el diagnóstico de las enfermedades relacionadas con el metabolismo del hierro / Hepcidin: Interaction with Hemojuvelin and its Contribution in the Diagnosis of Diseases Related to Iron Metabolism

La hepcidina es una hormona peptídica, producida en el hígado y considerada unregulador del metabolismo del hierro. Su regulación está dirigida a la absorciónintestinal del hierro y a la función de la ferroportina dentro de la célula, a fin demantener un balance entre el consumo y las reservas de hierro. Esta hormona, a suvez, está regulada por procesos inflamatorios, estados de anemia ferropénica, actividadhematopoyética y algunas vías de señalización como SMAD, STAT y JAK. En estasvías interviene una proteína de membrana llamada hemojuvelina, la cual actúa comoun correceptor de la proteína morfogenética ósea, cuya función es inducir el gende transcripción de la hepcidina mediante la vía SMAD1/5/8-SMAD4. Debido a laasociación de la hemojuvelina con la expresión de la hepcidina y la relación de estaúltima con procesos inflamatorios y regulación del metabolismo del hierro, se hanpropuesto algunas técnicas para la determinación de ambas proteínas como Elisa,Dotblot, inmunoensayos y SELDI-TOF MS...

The hepcidin is a peptide hormone produced by theliver with anti-bacterial activity, is involved in regulationiron metabolism, making it possible to useit as another parameter to assess some entities relatedto disorders associated with iron metabolism.Hepcidin regulates intestinal absorption of ironlevel and the role of ferroportin in the cell, preventingeither iron overload or iron consumptionreserve, this is turn regulating for inflammatorystimuli, iron store, erythropoietic activity andsignaling patway SMAD,STAT and JAK; in thissignaling patway involved a membrane proteincalled hemojuvelin. The hemojuvelin acts as abone morphogenetic protein co-receptor, theyinduce hepcidin gene transcription through theSMAD1/5/8-SMAD4. Because of the associationsof hemojuveline with hepcidin expression andthe relationship of the latter with inflammatoryprocesses and regulations of iron metabolismhave been proposed some techniques for the determinationof both proteins as Elisa, Dotblot,Immunoassays and SELDI-TOF MS...

Efectos sobre la salud y el medio ambiente de las actividades mineras en Chile: contaminación del Estero Pupío y agua potable del pueblo de Caimanes: ¿se origina desde el tranque de relaves mineros El Mauro? / Health and environmental effects of mining activities in Chile: Pupio River and Ddinking water pollution in the town of Caimanes: does it originate from the El Mauro mining tail?

Se describe la presencia de concentraciones elevadas de mercurio en el agua potable del pueblo de Caimanes y la presencia de concentraciones muy elevadas de manganeso, mercurio, hierro, níquel y molibdeno en el estero Pupío. La evidencia sugiere que estos niveles elevados de elementos tóxicos provienen de filtraciones del tranque de relaves El Mauro en la IV Región de Chile. Se describen los efectos diferidos de la exposición crónica y prenatal a estos elementos tóxicos.

The presence of high amounts of mercury in drinking water in the town of Caimanes and presence of very high concentrations of manganese, mercury, iron, nickel and molybdenum in the Pupio river is reported. Evidence suggests that these increased concentrations of toxic elements result from the El Mauro mining tail filtrations in the IV Region of Chile. The delayed effects of chronic and prenatal exposure to these toxic agents are described.

A suplementação de ferro na gravidez: orientações atuais / Iron supplementation in pregnancy: current guidelines

O ferro é um dos minerais mais abundantes na crosta terrestre e nos organismos. Participa da síntese da hemoglobina, mioglobina, além de ser co-fator de uma série de reações enzimáticas. Durante a gravidez, vários processos fisiológicos fazem com que a demanda desse micronutriente tenha um incremento significativo, o que torna necessárias maiores ingestão e absorção de ferro. Sabe-se que, durante a gestação, a quantidade de ferro absorvida nos intestinos aumenta, mas, mesmo assim, a maioria das gestantes não ingere quantidade satisfatória desse mineral, o que torna explicável a suplementação oral da dieta com ferro. Vários autores advogam que essa suplementação não deva ser feita de maneira rotineira, mas individualizada, devido a possíveis efeitos deletérios do ferro durante a gestação, dentre eles o aumento nas taxas de Diabetes Mellitus Gestacional e pré-eclâmpsia. O objetivo desse estudo é realizar uma revisão na literatura médica que versa sobre o assunto, criando uma análise crítica sobre a suplementação oral rotineira de ferro e seus possíveis riscos durante a gestação

Iron is one of the most abundant mineral on the Earth's crust and organisms. It is essential for the synthesis of hemoglobin and myoglobin; besides, it acts as a co-factor in a series of enzymatic reactions. During pregnancy, multiple physiological adaptations cause an increase in the demand of micro-nutrients, which makes further ingestion and absorption of iron necessary. It is known that, during pregnancy, the amount of iron absorbed in the intestines increases, but even so, most pregnant women do not have an adequate iron intake, which makes the oral supplementation of diet with iron a reasonable action. A considerable number of authors advocate that this supplementation should not be made as a routine, but individualized, due to the possible deleterious effects of iron during pregnancy, among them the increased risk of Gestational Diabetes and pre-eclampsia. The aim of this study is to perform a review in the medical literature about the subject, creating a critical analysis of routine iron supplementation and its possible risks during pregnancy

Constipação intestinal e gravidez / Constipation in pregnancy

A constipação intestinal é queixa frequente no atendimento obstétrico, e está associada a dificuldades na defecação, seja pelo emprego de força e/ou diminuição de frequência na evacuação. Na gravidez, além dos fatores relacionados à dieta, como a baixa ingestão de fibras e água, outros contribuem para a piora deste sintoma, tais como: suplementação de ferro, redução na atividade física, motilidade reduzida do cólon e os efeitos hormonais sobre a motilidade gastrintestinal. Apesar de a anamnese detalhada permitir a identificação da constipação, alguns critérios específicos são propostos para auxiliar o reconhecimento deste sintoma. Entender a constipação no período gestacional é importante, pois é condição comum que leva a queixas nas consultas médicas resultando em altos custos para a saúde pública. O maior conhecimento dos fatores associados a este sintoma pode auxiliar no tratamento e delineamento de estratégias de conduta, visando melhorar a qualidade de vida das gestantes afetadas pela constipação.

Constipation is a frequent complaint in obstetric care, and is associated with difficulties in defecation, either by using force and/or decreased frequency in the evacuation. In pregnancy, in addition to dietary factors, such as low intake of fiber and water, iron supplementation, reduction in physical activity, reduced colonic motility and the hormonal effects on gastrintestinal motility also contribute to the worsening of this symptom. Although the detailed history of constipation can be identified, some specific criteria are proposed to assist the recognition of this symptom. Understanding constipation during pregnancy is important because it is a common condition that leads to complaints in medical consultations resulting in high costs to public health. Knowledge of the factors associated with this symptom may help to establish treatments and to manage strategies to improve the quality of life of pregnant women affected by constipation.

Rapid iron loading in heart and liver in a patient with transfusion dependent thalassaemia after brief poor compliance with iron chelation therapy

Iron loading in patients with transfusion dependent thalassaemia is considered to occur primarily in the liver and, once the liver becomes saturated, other organs begin loading. We report here a splenectomised male patient who was treated for hepatitis C virus infection. Prior to starting antiviral therapy, his serum ferritin was maintained below 500 ng/ml with deferiprone monotherapy; cardiac T2[*] by magnetic resonance imaging was 48.8ms and hepatic T2[*] was 19.5ms. After twelve months of antiviral treatment during which time he was very poorly compliant with his deferoxamine chelation therapy, his ferritin had risen to 3820 ng/ml and cardiac and hepatic T2[*] findings were 12.7 ms and 14.5 ms respectively, indicating increased iron loading in both organs, but particularly in the heart. Fifteen months after recommencing combination chelation, his ferritin was 95 ng/ml and cardiac and hepatic T2[*] were 27.5 and 28.4ms respectively, indicating complete clearance of iron load in both organs. This case demonstrates that iron overload can develop rapidly and in some cases there is relatively rapid iron loading in the heart as compared to the liver

Advances in management of thalassemia.

Thalassemias represent the most common single-gene disorder causing a major public health problem in India. Thalassemia and hemoglobinopathies probably developed over 7000 years ago as a defense against malaria. In simple terms, thalassemia is caused by a mutation in either the â-globin chain or the á-globin chain which combine equally in red cells to form hemoglobin. These mutations lead to varying degree of anemia resulting into thalassemia minor, intermedia or major. Present write up relates to advances in the management of â-thalassemia major.

Iron status in preeclampsia

To evaluate iron status in pregnancy induced hypertension and role of iron in the etiology and pathogenesis of pre-eclampsia. Coefficient correlation study. At Department of Biochemistry, Frontier Medical College, Abbottabad with collaboration of Department of Obstetrics and Gynecology, Ayub Medical Complex, Abbottabad from March 2006-March 2007. Study was performed on hundred pregnant women of age ranging between 15-35 years and having gestational age between28 to 34 weeks. Fifty obstetric patients were identified as having pre-eclampsia. Fifty healthy pregnant subjects were taken as controls, having uncomplicated pregnancies and were normotensive throughout gestation and without proteinuria. Results depicts that mean age of pre-eclamptic group was significantly low [P<0.001] as compared to control. Both parameters, Hemoglobin and Haematocrit were significantly higher [P<0.05] in pre-eclamptic as compared to controls. Serum iron, serum ferritin and transferrin saturation were significantly higher [P<0.001] in pre-eclamptic in comparison with control group. Total iron binding capacity and unsaturated iron binding capacity were significantly lower [P<0.001] in pre-eclamptic group when compared to control group. Correlation coefficient between serum iron, total iron binding capacity [TIBC], serum ferritin, unsaturated iron binding capacity [UIBC] and systolic and diastolic blood pressure in pre-eclamptic group showed no significant positive correlation in any parameter. It is concluded that hemoglobin, haematocrit, serum iron, serum ferritin and transferrin saturation are significantly increased in pregnant women that later develops pre-eclampsia. Excess iron is postulated as casual factor in the oxidative stress ie; in its radical form, which may be involved in the pathogenesis of pre-eclampsia. Therefore, iron status of pregnant women should be assessed before giving iron supplements as these may cause more harm than benefit

Efecto de altos niveles de hierro y molibdeno sobre la nutrición del cobre en vacas mestizas / High levels of dietary iron and molybdenum on copper nutrition in cross bred cows

Para estudiar el efecto de altos niveles de hierro (Fe) y molibdeno (Mo) sobre la nutrición del cobre (Cu), 20 vacas vacías, mestizas Bos taurus x Bos indicus, de 394 kg PV y de más de dos partos, fueron distribuidas según un diseño completamente aleatorizado en los siguientes tratamientos: (1) Testigo (T): 10 ppm Cu; (2) Mo: 10 ppm Cu y 20 ppm Mo; (3) Fe: 10 ppm Cu y 1000 ppm Fe; (4) MoFe: 10 ppm Cu y 1000 ppm Fe y 20 ppm Mo. Las vacas fueron alimentadas ad libitum con pasto de corte (Panicum maximun y Andropogun gayanus), 1,5 kg de alimento por animal día -1 (harina de maíz: 95 por ciento; urea: 5 por ciento) que contenía los minerales en las proporciones indicadas. Se tomaron muestras de suero sanguíneo para determinar Cu, Fe y la actividad de la ceruloplasmina. A través de biopsias, se tomaron muestras del tejido hepático cada 28 días, durante 192 días, para determinar la concentración de Cu, Fe y Mo. El consumo de pasto estuvo alrededor de 10 kg MS/animal día -1. El peso vivo no presentó diferencias entre tratamientos con valores de 385; 353; 396 y 382, kg para T, Mo, Fe, MoFe, respectivamente. La concentración de Cu sérico (µg ml-1) fue de 0,81; 0,67; 0,50 y 0,71, respectivamente para el mismo orden de los tratamientos, siendo Fe el más bajo (P<0,05). Para el Fe sérico, se observaron diferencias significativas entre los tratamientos (P<0,05), con valores de 1,49; 1,67; 2,08 y 1,93 µg ml -1, para el testigo, Mo, Fe y MoFe, respectivamente. Los valoresde Cp (absorbancia) fueron 0,093; 0,085; 0,084 y 0,087, para el testigo, Mo, Fe y MoFe, respectivamente, sin diferencias significativas entre tratamientos. Los niveles de Cu hepático fueron diferentes (P<0,01) entre tratamientos, con valores más altos (mg kgMS-1) para T (71,9) y más bajos para Mo (26,6), Fe (30,8) y MoFe (31,4). La concentración de Fe en el hígado registró valores (mg kgMS-1) de 559,0; 513,3; 559,8 y 797,3para T, Mo, Fe y MoFe, respectivamente, sin diferencias significativas...

To evaluate the effect of high levels of iron (Fe) and molybdenum (Mo) on copper (Cu) nutrition, 20 dry cross bred cows, Bos Taurus x Bos indicus, of 394 kg BW, with no less than two calving, were assigned to the following treatments: (1) Control (C); 10 ppm Cu(2); Mo 10 ppm + 20ppm Cu (Mo); (3) 10ppm Cu+ 1000 ppm Fe (Fe); and (4) 10 ppmCu+ 1000 ppm Fe+ 20 ppm Mo ( MoFe). Cows were fed chopped forage ad libitum (Panicum maximum and Andropogun gayanus) and 1.5 kg concentrate feed (corn meal, 95% and urea, 5%) containing minerals in the proportions as previously indicated. Serum samples were taken every 28 days for Cu, Fe and cerulopasmine (Cp) activity. Liver sample, via biopsy, at the same time intervals, were also taken to measure Cu, Fe and Mo concentrations. The experiment lasted 192 days. Body weights were not affected by treatments: 385; 353; 396 and 382 kg, respectively for T, Cu, Fe,and MoFe. Copper serum concentration values (µg ml-1) were 0.81, 0.67, 0.50 and 0.71, respectively for the same order, being Fe the lowest (P<0.05). Ceruloplasmine absorbancy values were not different among treatments. Liver copper concentration values were significantly different (P<0.05) among treatments, with higher value (mg KgMS-1) for T (71.9) and lower for Mo (26.6), Fe (30.8) and MoFe (31.4). Liver iron concentration (mg kgMS-1) values were not different among treatments, with values of 559.0, 513.3, 559.8, and 797.3 respectively for C, Mo, Fe and MoFe. Liver Mo take up (mg kgMS-1) was greater (P<0.01) for Mo treatment (19.9) and MoFe (15.8) in relation to T (1.7) and Fe (1.9). Results indicate that high levels of Mo and Fe decreased liver copper, below critical levels. However, the reduction of liver copper was no associated with clinical sign of copper efficiency. Probably lower levels of liver copper are required to show changes in ceruloplasmine and blood serum concentrations as well as other biochemical changes at tissue level...

Redox-active labile iron in fortified flours from the Brazilian market

OBJECTIVE: To quantify the fraction of redox-active labile iron in iron-fortified flours acquired on the Brazilian market. METHODS: Samples of wheat flour, maize flour and breadcrumbs were extracted with buffers that mimic gastric juice, saliva and intestinal juice. Redox-active labile iron levels were assessed through the reaction of autoxidation of ascorbic acid catalyzed by iron in the presence of a fluorescence probe. RESULTS: Redox-active labile iron represents 1 percent to 9 percent of the total iron in the flour and breadcrumb samples, with the lowest values found under gastric juice conditions and the highest in the more alkaline media. Redox-active labile iron possibly arises from the decomposition of an iron-phytic acid complex. A positive correlation between redox-active labile iron and total iron was found in saline biomimetic fluids. CONCLUSION: Redox-active labile iron may be a risk factor for people with impaired antioxidant defenses, such as those who are atransferrinemic or iron overloaded (e.g. thalassemic). Total iron can be used to predict redox-active labile iron absorption at each stage of the gastrointestinal tract after ingestion of iron-fortified flours.

OBJETIVO: Quantificar a porcentagem de ferro lábil redox ativo em farinhas fortificadas adquiridas no comércio popular. MÉTODOS: Amostras de farinha de trigo, fubá e rosca foram extraídas com tampões miméticos de suco gástrico, saliva e suco intestinal. Os níveis de ferro lábil redox ativo foram determinados por meio da reação de auto-oxidação do ácido ascórbico catalisada pelo ferro, em presença de uma sonda fluorimétrica. RESULTADOS: A fração de ferro lábil redox ativo representa entre 1 por cento e 9 por cento do ferro total nas farinhas estudadas, sendo os menores valores encontrados em condições miméticas do suco gástrico e os maiores nos meios mais alcalinos. Há indícios de que o ferro lábil redox ativo origina-se da decomposição de um complexo entre ferro e ácido fítico. Observa-se uma correlação positiva entre ferro lábil redox ativo e ferro total nas condições de salinidade dos fluidos biomiméticos estudados. CONCLUSÃO: Ferro lábil redox ativo pode ser um fator de risco para pacientes atransferrinêmicos, sistemicamente sobrecarregados com ferro (por exemplo, talassêmicos) ou aqueles com defesas antioxidantes comprometidas por enfermidades. A quantidade de ferro total pode ser preditiva dos níveis de ferro lábil redox ativo absorvidos em cada etapa do trato gastrintestinal após a ingestão de farinhas fortificadas.

Comparative effects of copper, iron, vanadium and titanium on low density lipoprotein oxidation in vitro

Oxidation of low density lipoprotein [LDL] has been strongly implicated in the phathogenesis of atherosclerosis. The use of oxidants in dietary food stuff may lead to the production of oxidized LDL and may increase both the development and the progression of atherosclerosis. The present work investigated the effects of some elements including: copper [Cu], iron [Fe], vanadium [V] and titanium [Ti] on in vitro LDL oxidation quantitatively. The first LDL fraction was isolated from fresh plasma by single vertical discontinuous density gradient ultracentrifugation. The formation of conjugated dienes and thiobarbituric acid reactive substances and increase in electrophoretic mobility of LDL were monitored as markers of the oxidation of LDL. It was demonstrated that Cu, Fe, V and Ti exhibited strong oxidant activity in this respect [P<0.001]. Oxidation of LDL in the presence of Cu was more and appeared to be in this order Cu>Fe> V>Ti. Discussion: Cu, Fe, V and Ti are redox-active transition metals that may cause oxidative damage to lipids, proteins and DNA molecules. We suggest that these elements may also influence the oxidation of LDL in vivo, which could increase both the development and progression of atherosclerosis

Estudio toxicológico de un inyectable apócrifo conteniendo hierro como principio activo / Toxicological study of a counterfeit medicinal product containing iron sorbitol

Una mujer embarazada murió luego de la administración parenteral de un preparado de hierro (sorbitol),producto que fue identificado por la Autoridad Sanitaria Argentina como un medicamento apócrifo. Su análisis químico determinó que el contenido de hierro era 3.5 veces mayor al rotulado. Los estudios toxicológicos demostraron que su administración representa un riesgo sanitario y podría ser el causante de la muerte.

After the injection of an iron sorbitol preparation a pregnant woman died. Its chemical analysis determined a hugeamount of iron (3.5-fold higher than the labeled). Results obtained by toxicological studies show that such medicinal product represents a sanitary risk and probably it could be presumed as the cause of death.

Assessment of adrenal endocrine function in Asian thalassemics.

Adrenal endocrine function was assessed in a cohort of 20 patients, between 10 and 20 years of age, with transfusion dependent beta thalassemia. Cortisol levels were assayed before and after ACTH stimulation with 1 micrograms and 250 micrograms. Adrenal dysfunction was defined as a basal cortisol of greater than 400 nmol/L and/or peak cortisol levels of greater than 500 nmol/L. Overall, 9 patients (45 %) had in vitro evidence of adrenal dysfunction. A statistical significant correlation (r=0.4308; P < 0.05), between wasting and the basal cortisol level, was observed. Similarly, there was correlation between the number of transfusions received and growth failure (r=0.4774;P < 0.05). In comparison to the involvement of other endocrine axes in polytransfused thalassemics, the adrenal endocrine function abnormalities are minor and clinically of little consequence. The observations, albeit, in a small cohort of thalassemics, stress the need for an annual estimation of basal cortisol level, especially in patients with wasting.