Cytokine distribution in mothers and breastfed children after omega-3 LCPUFAs supplementation during the last trimester of pregnancy and the lactation period: A randomized, controlled trial.

OBJECTIVE: To determine whether maternal diet supplementation with omega-3 long chain polyunsaturated fatty acids (omega-3 LC-PUFAs) during the last trimester of pregnancy and the breastfeeding period influences the levels of inflammatory cytokines in mother and infants. MATERIAL AND METHOD: This registered, double-blind randomized study included 46 pregnant women, who were randomly allocated to either an experimental group receiving 400mL/day of a fish oil-enriched dairy drink [320mg docosahexaenoic acid (DHA) + 72mg eicoapentaenoic acid] (FO group, n = 24) or to a control group receiving 400mL/day of a non-supplemented dairy drink (CT group, n = 22), from week 28 of pregnancy until the fourth month of lactation. During the study, maternal dietary patterns were monitored by a nutritionist, who encouraged compliance with current recommendations of fatty acids intake. DHA concentrations and cytokine levels (GM-CSF, IL-2, IL-4, IL-6, IL-10, INF-γ and TNF-α) were measured in maternal plasma at the moment of recruitment and in maternal (n = 46) and infant (n = 46) plasma at birth and 2.5 months after birth. RESULTS: Maternal plasmatic IL-4 levels were higher in FO than in CT subjects (p = 0.009). Additionally, a tendency was observed to higher IL-10 and IL-2 in the FO group. Plasmatic IL-6 however, was higher in CT mothers (p = 0.001). TNF-α was higher in CT infants at birth and 2.5 months after birth (p = 0.005). An analysis of possible relationships between DHA and the concentrations of different cytokines revealed negative correlation between maternal plasmatic IL-6 and DHA (higher plasmatic DHA corresponded to lower IL-6). CONCLUSIONS: Maternal dietary omega-3 LC-PUFAs supplementation during critical periods like pregnancy, lactation and early newborn development may influence the levels of certain inflammatory cytokines, reducing pro-inflammatory cytokines and promoting an anti-inflammatory "environment".

The Benefits of Administering Folic Acid in Order to Combat the Oxidative Damage Caused by Binge Drinking in Adolescent Rats.

AIMS: An important mechanism in alcohol-induced injury is biomolecular oxidative damage. Folic acid is supplied to chronic alcoholic patients in order to prevent this situation, as this is the main vitamin deficiency that they suffer from. Acute alcohol exposure, such as binge drinking, is one of the most widespread ethanol consumption models practiced by adolescents. However, there is no evidence of folic acid body profiles after this pattern of consumption. METHODS: Four groups of adolescent rats were used: control, alcohol (exposed to intraperitoneal binge drinking), control folic acid-supplemented group and alcohol folic acid-supplemented group. Folic acid levels, protein, lipid and DNA oxidative damage in serum, and liver glutathione (GSH) and reduced/oxidized glutathione ratio (GSH/GSSG) were measured. RESULTS: Binge-drinking rats had higher lipids and DNA oxidation levels. They also had lower hepatic GSH levels and GSH/GSSG ratio. Folic acid supplementation to binge-drinking rats does not change the serum protein oxidation but decreases lipid and DNA oxidation. Finally, GSH increased to control levels with folic acid supplementation. CONCLUSION: Folic acid supplementation is an economic and efficient therapy against the oxidative damage in lipids and mainly in DNA stability caused by binge drinking during adolescence. It has also been demonstrated that folic acid increases GSH levels, improving the antioxidant status and revealing a hepatoprotective effect during binge drinking.

Goat milk consumption modulates liver divalent metal transporter 1 (DMT1) expression and serum hepcidin during Fe repletion in Fe-deficiency anemia.

Iron deficiency is the most prevalent micronutrient deficiency worldwide. In spite of the crucial role of hepatocyte divalent metal transporter 1 (DMT1) and hepcidin in Fe metabolism, to date, no studies have directly tested the role of these proteins in liver Fe metabolism during Fe repletion after induced Fe-deficiency anemia. Therefore, the aim of the current study was to assess the effect of goat or cow milk-based diets on Fe metabolism in one of the main body storage organs, the liver, during the course of Fe repletion with goat or cow milk-based diets in anemic rats. Animals were placed on a preexperimental period of 40 d, a control group receiving a normal-Fe diet and the Fe-deficient group receiving a low-Fe diet (5 mg of Fe/kg of diet). Rats were fed for 30 d with goat or cow milk-based diets with normal Fe content (45 mg of Fe/kg of diet). The hematological parameters, serum hepcidin, hepatosomatic index, liver Fe content, and liver DMT1 expression were determined. During the recovery of the anemia with milk-based diets, the restoration of liver Fe content and hematological parameters, especially with goat milk, increased the red blood cell count, favoring the oxygen supply and weight gain. Moreover, goat milk consumption potentiates liver DMT1 expression, enhancing Fe metabolism and storage. In addition, the increase in serum hepcidin in anemic rats observed in the current study also explains and supports the higher liver Fe content after supplying goat milk, because it blocks the liberation of Fe from hepatocytes, increasing its storage in liver.

Advantages and disadvantages of the animal models v. in vitro studies in iron metabolism: a review.

Iron deficiency is the most common nutritional deficiency in the world. Special molecules have evolved for iron acquisition, transport and storage in soluble, nontoxic forms. Studies about the effects of iron on health are focused on iron metabolism or nutrition to prevent or treat iron deficiency and anemia. These studies are focused in two main aspects: (1) basic studies to elucidate iron metabolism and (2) nutritional studies to evaluate the efficacy of iron supplementation to prevent or treat iron deficiency and anemia. This paper reviews the advantages and disadvantages of the experimental models commonly used as well as the methods that are more used in studies related to iron. In vitro studies have used different parts of the gut. In vivo studies are done in humans and animals such as mice, rats, pigs and monkeys. Iron metabolism is a complex process that includes interactions at the systemic level. In vitro studies, despite physiological differences to humans, are useful to increase knowledge related to this essential micronutrient. Isotopic techniques are the most recommended in studies related to iron, but their high cost and required logistic, making them difficult to use. The depletion-repletion of hemoglobin is a method commonly used in animal studies. Three depletion-repletion techniques are mostly used: hemoglobin regeneration efficiency, relative biological values (RBV) and metabolic balance, which are official methods of the association of official analytical chemists. These techniques are well-validated to be used as studies related to iron and their results can be extrapolated to humans. Knowledge about the main advantages and disadvantages of the in vitro and animal models, and methods used in these studies, could increase confidence of researchers in the experimental results with less costs.

The effects of ethanol upon hydric balance and arterial pressure in rats: folic acid as a possible hypotensor.

AIMS: Chronic alcohol intake is related to hypertension. There are, however, few studies concerning the effect of ethanol upon hydric balance in relation to arterial pressure. Folic acid intake has beneficial effects upon the cardiovascular system decreasing hyperhomocysteinemia, however, more studies imply that it is related with other mechanisms. Therefore, we have studied the effects of chronic alcohol intake (30% v/v) upon hydric-saline balance and hypertension and have found that dietary supplementation with folic acid (8 mg/kg) improves the above parameters. MAIN METHODS: Our study used four experimental groups of rats: control, alcohol, alcohol with folic acid and control with folic acid. In all cases we measured the clearance of Na(+), K(+) and aldosterone; osmolarity in urine, liquid and solid ingestion; homocysteine levels in serum; cardiac frequency and arterial blood pressure. KEY FINDINGS: The alcohol intake increases serum aldosterone and homocysteine, which is reflected in an increase in arterial blood pressure. In addition, we have found that alcohol intake reduces both liquid and solid ingestion (causing a malnourishment status), the clearance of creatinine, aldosterone, Na(+) and K(+), and the ratio ClNa(+)/ClCr; it also increases urine osmolarity. Folic acid supplementation increases the clearance of Na(+) and the ratio ClNa(+)/ClCr. SIGNIFICANCE: Folic acid intake improves the hypertension provoked by alcohol by increasing the aldosterone clearance, drastically reducing the serum levels of this hormone and thus its hypertensor effect.

Goat milk during iron repletion improves bone turnover impaired by severe iron deficiency.

The effect of goat or cow milk-based diets, with either normal Fe content or an Fe overload, on bone turnover and the mineralization process was studied in control and anemic rats during chronic Fe repletion. One hundred eighty male Wistar rats were studied during a pre-experimental period of 40 d in which they were randomly divided into 2 groups, a control group receiving the AIN-93G diet with normal Fe content (45 mg/kg of diet) and the Fe-deficient group receiving the AIN-93G diet with low Fe content (5mg/kg of diet) for 40 d. After the pre-experimental period, the rats were fed for 10, 30, or 50 d with goat or cow milk-based diets with a normal Fe content (45 mg/kg of diet) or an Fe overload (450 mg/kg of diet). In anemic rats, goat milk with normal Fe content increased levels of the biomarker of bone formation N-terminal propeptides of type I procollagen and diminished parathyroid hormone levels after only 10 d of supplying this diet, indicating the beginning of restoration of the bone demineralization induced by the anemia, which was not observed with cow milk. After 30 d of supplying the milk-based diets with normal Fe content or an Fe overload, biomarkers of bone formation and bone resorption were not different between control and anemic rats, indicating that the bone demineralization induced by the Fe-deficiency anemia had recovered, although the process of stabilization of bone turnover began earlier in the animals fed goat milk. In addition, a higher Ca deposit was observed in femur, which positively affects bone mineralization, as well as an increase of Fe in sternum, which indicates that the hematopoietic process essentially recovered earlier on the goat milk diet compared with the cow milk diet.

Efecto de la anemia ferropénica nutricional sobre el contenido en hueso de Ca, P y Fe / Iron deficiency anemia effect of nutrition on the content in bone, Ca, P and Fe

La anemia ferropénica nutricional provoca una alteración de gran importancia en el metabolismo fosfocálcico. Con este estudio pretendemos comprobar cómo la anemia ferropénica nutricional afect ael depósito de Ca y P en fémur y el contenido de Fe en esternón, para ello determinamos Fe y Ca por espectrofotometría de absorción atómica y de P por espectrofotometría ultravioleta visible en ratas macho raza Wistar albina ferrodeficientes. El depósito de Ca y P en el fémur es significativamente (P <0.001) más bajo para el grupo anémico. Esto puede deberse al incremento de los niveles séricos de PTH y cortisol, inducidos por la ferrodeficiencia severa (Campos y col., 2007). Además se produce una drástica disminución (P < 0.001) en el contenido de Fe en esternón, hecho que incide de manera muy negativa en el proceso hematopoyético(AU)

Nutritional iron-deficiency anemia provokes a noteworthy alteration in the phosphorus and calcium metabolism. With the current study we tried to check how the nutritional iron deficiency anemia affects Ca and P deposit in femur and the Fe content in sternum. We determined Fe and Ca by atomic absorption spectrophotometry and P by ultraviolet /visibly spectrophotometry in Fe-deficient male wistar albino rats. Ca and P deposit in femur is significantly lower in the anaemic group. This can be due to the increase of the serum levels of PTH and cortisol, induced by the severe Fe-deficiency. In addition, a drastic decrease in the Fe content in sternum was recorded, fact that affects in a very negative way in the haematopoietic process(AU)

Utilización nutritiva de hierro en el transcurso de la ferrodeficiencia / Nutritive utilization of iron during the evolution of a iron deficiency

Se ha estudiado la utilización digestiva y metabólica de hierro durante la evolución (20,30, 40 días) de una ferrodeficiencia nutricional en ratas en periodo de crecimiento. Se han usado 48 ratas (Ratusnovergicus, raza Wistar albina) con un peso inicial aproximado de 45-50. Los animales se dividieron en 6 grupos: tres grupos controles (C) y tres grupos ferrodeficientes (FD) que recibieron una dieta AIN93G con contenido normal (45 mg Fe/kg dieta) o con un bajo contenido de hierro (5 mg/Fe Kg dieta)respectivamente durante 20, 30 ó 40 días. Los resultados obtenidos indican que la utilización nutritiva de hierro aumenta progresivamente en todos los periodos, siendo esta diferencia significativa, si comparamos el día 40 con el 20, esto es debido a que dicha patología produce una depleción de los depósitos corporales de Fe, lo cual favorece la entrada a favor de gradiente de concentración por difusión simple de dicho mineral(AU)

The digestive and metabolic utilization of iron during the evolution (20, 30, 40 days) of a nutritional Fe-deficiency has been studied in growing rats. 48 rats (Ratus novergicus, Wistar albino breed) wereused with an initial approximate weight of 45-50g. The animals were divided in 6 groups: three groups control (C) and three groups Fe-deficient (FD) receiving a diet AIN 93G with normal-Fe content (45mg/kg diet) or with a low-Fe content (5 mg/Kg diet) respectively during 20, 30 ó 40 days. The results obtained indicate that the nutritive utilization of iron increases progressively in all the periods, being this difference significant, if we compare the day 40 with 20, due to the above mentioned pathology produces a depletion of the Fe body stores, which favours the up take in favour of gradient of concentration by simple diffusion(AU)

Utilización nutritiva de fósforo en el transcurso de la anemia ferropénica nutricional / Nutritive utilization of phosphorus during the course of nutritional ferropenic anaemia

Se ha estudiado el efecto de la evolución de la anemia ferropénica nutricional sobre la utilización digestiva y metabólica de fósforo en tres periodos 20, 30 y 40 días. Los animales de experimentación han sido 48 ratas macho de la raza Wistar albina que se dividieron en 6 grupos: tres grupos controles(C) y tres grupos ferrodeficientes (FD) que recibieron una dieta AIN 93G con contenido normal (45mg Fe/kg dieta) o con un bajo contenido de hierro (5 mg/Fe Kg dieta) respectivamente durante 20, 30 ó 40 días. Se ha encontrado un aumento significativo en la utilización digestiva y metabólica de fósforo en el transcurso de la anemia ferropénica nutricional, efecto que se va haciendo más patente a medida que evoluciona la ferrodeficiencia. Este incremento en la utilización nutritiva de fósforo es debido principalmente al mecanismo pasivo de absorción de fósforo que opera principalmente en el yeyuno-íleon y es predominante en situación de anemia ferropénica nutricional(AU)

The evolution of the nutritional iron deficiency anemia on the digestive and metabolic utilization of phosphorus has been studied during three periods: 20, 30 and 40 days. 48 male Wistar albino breedrats were divided in 6 groups: three control groups (C) and three Fe-deficient groups (FD) receiving AIN 93G with normal-Fe content (45 mg /kg diet) or with a low-Fe content (5 mg/Kg diet) respectively during 20, 30 ó 40 days. A significant increase in the digestive and metabolic utilization of phosphorus has been found in the course of the nutritional iron deficiency anemia, effect that become more pronounced as the ferrodeficiency is instaured. This increase in the nutritive utilization of phosphorus is due mainly to the passive mechanism of phosphorus absorption which operates principally in the jejunum-ileum and is predominant in situation of nutritional iron deficiency anemia(AU)

Relación hepatosomática y depósito de hierro en hígado durante la instauración de anemia ferropénica nutricional / Hepatosomatic index and iron liver stores during the instauration of nutritional ferropenic anaemia

El hígado es el principal órgano de almacén de hierro en el organismo y juega un papel crucial en la homeostasis de dicho mineral. Los niveles de hierro en se consideran un fiel reflejo del estatus de hierro en el organismo, hecho que nos indujo a determinar la relación hepatosomática y el contenido de hierro en hígado durante la instauración de la anemia ferropénica nutricional inducida experimentalmente en ratas en crecimiento. Los depósitos de hierro estaban profundamente deplecionados, el peso corporal y el peso hepático fue menor en animales anémicos. Como consecuencia, la relación hepatosomática se incrementó en animales ferrodeficientes. Durante la ferrodeficiencia, varios factores reguladores de la hepcidina se alteran, aumenta la demanda eritropoyética por disminución de los parámetros hematológicos, hay un menor aporte de oxígeno a los tejidos y se deplecionan los depósitos corporales, alterándose el metabolismo de hierro, hechos que conducen a una disminución de dicha hormona, lo cual se traducirá en una menor interacción con la ferroportina 1, evitando su internalización y degradación, de manera que aumenta el flujo de salida de hierro ferroso desde los hepatocitos y consecuentemente se reduce su depósito. Por otra parte, la ferrodeficiencia afectó el peso corporal, hecho que se puede atribuir a los menores niveles de hormonas tiroideas encontrados en esta patología. Puesto que hay una clara reducción de la hemoglobina y recuento de hematíes, el suministro de oxígeno a las células se limita considerablemente e incide negativamente en la síntesis de ATP e incremento de peso(AU)

Liver is main storage organ of iron in the organism and plays a crucial role in the homeostasis of this mineral. The levels of iron are considered a routine index of the iron status in the body, fact that encouraged us to asses the hepatosomatic index and the iron content in liver, during iron-deficiency anaemia in growing rats. In rats with iron-deficiency anaemia, iron deposits were deeply depleted, body weight and hepatic weight were lower, moreover the hepatic iron deposits were lower in anaemicrats. During the iron-deficiency, several regulatory factors of the hepcidin are impaired (the erythropoietic demand increase due to the decrease of the haematological parameters, there is a minor supply of oxygen to the tissues and the body stores are depleted, being the iron metabolism altered), facts that leads to a decrease of the above mentioned hormone, which will be translated in a minor interaction with the ferroportin1, avoiding its internalization and degradation, therefore increases the outflow of ferrous iron from the hepatocytes and consistently its storage diminishes in the above mentioned organ. On the other hand, the iron-deficiency impaired the body weight, fact that can be related with the lower levels of thyroid hormones found in this pathology. Moreover, since in iron deficiency situation the haemoglobin and red blood cells count diminish drastically, the supply of oxygen to the cells limits itself considerably, which affects in a negative way to the ATP synthesis andincrease of weight(AU)

Utilización nutritiva de magnesio durante el desarrollo de la anemia ferropénica nutricional / Nutritive utilization of magnesium during the development of nutritional iron deficiency anaemia

Dada la alta prevalencia de la anemia ferropénica y la diversidad de población a la que afecta es de interés conocer durante el desarrollo de la anemia las repercusiones de la deficiencia de hierro sobre el aprovechamiento nutritivo de otros minerales como el magnesio, para ello se ha determinado la utilización digestiva y metabólica a los 20, 30 y 40 días de suministrar una dieta con bajo contenido en hierro en ratas en crecimiento. La anemia incrementa la utilización nutritiva de magnesio en el día 30 del estudio. En los tres periodos estudiados, la utilización digestiva de magnesio en ratas controles presenta valores similares; en cambio, la relación magnesio retenido respecto al ingerido se eleva significativamente dadas las menores pérdidas urinarias de este mineral hacia el final del estudio. En ratas anémicas, el aprovechamiento digestivo y metabólico de magnesio aumenta en los últimos periodos estudiados debido al incremento del componente pasivo de la absorción de magnesio, ya que en situación de ferrodeficiencia la energía metabólica está disminuida y por tanto el componente activo de la absorción se encuentra reducido considerablemente(AU)

Taking into account the high prevalence of the iron deficiency anemia and the diversity of population affected, it is of great interest to know the repercussions of the iron deficiency during the development of the pathology on the nutritive utilization of other minerals such as magnesium, therefore we decided to study the digestive and metabolic utilization to 20, 30 and 40 days of supplying a diet with low content in iron in growing rats. The anemia increases the nutritive utilization of magnesium in the day 30 of the study. In the three studied periods, the digestive utilization of magnesium in control rats shows similar values; on the other hand, the relation magnesium retained with regard to the intake rises significantly because of the lower urinary losses of this mineral towards the end of the study. In anaemic rats, the digestive and metabolic utilization of magnesium increases in the last periods studied due to the increase of the passive component of the absorption of this mineral, since in situation of Fe-deficiency the metabolic energy is diminished and therefore the active component of the absorption is reduced considerably(AU)