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Adipose tissue is an endocrine organ and has central role in interaction with other organs or tissues while propolis can induce lipolysis. Therefore, the aim of this study is to provide detailed information about adipose tissue homeostasis modifications and body composition during propolis supplement consumption. Twenty male Wistar albino rats (8 weeks) were divided into two groups of 10 animals each and fed for 90 days with two different types of diets: standard for the control group (diet C) and standard diet + 2% propolis (diet P). Thyroid hormones did not show differences, while ghrelin and adiponectin decreased in the group that was fed propolis. Insulin, leptin, and non-esterified fatty acids also increased along with reduced body weight and fat, in addition to increased lean mass when propolis was in the diet. We conclude that propolis could decrease ghrelin and adiponectin but increase non-esterified fatty acids and insulin secretion, which improves body composition.

Periodontal disease encompasses gingivitis and periodontitis and is one of the most common chronic infections in the adult population. This study aimed to evaluate the influence of Spanish propolis extract (EEP) on the effect of the clinical and microbiological parameters as an adjuvant to scaling and root planning in patients undergoing supportive periodontal therapy (SPT). Forty chronic periodontitis patients were randomly assigned into two groups for the treatment. In the control group (n = 20), the sites were treated by scaling and root planing followed by gingival irrigation with physiological saline and in the test group (n = 20), the sites were treated by scaling and root planing followed by subgingival placement of EEP. At baseline (BL), bleeding on probing positive (BOP+) sites with probing pocket (PPD) ≥ 4 mm were defined as study sites. Plaque index, PPD, BOP, clinical attachment level (CAL), and subgingival plaque were evaluated at BL and 1 month later. The results showed a significant clinical improvement (p &lt, 0.05) in the PPD, CAL and BOP+ comparing them with BL and one month after the periodontal treatment and a significant reduction (p &lt, 0.05) for Tannerella forsythensis, Porphyromonas gingivalis, Prevotella intermedia and Treponema denticola in both groups. In addition, the improvement of clinical parameters was observed with subgingival use of EEP and also statistically significant differences between groups were observed (p &lt, 0.05) such as reductions of BOP+ % and reduced counts of T. forsythensis and P. gingivalis, considered as the “key pathogens” for the periodontal diseases. Our results suggest prophylactic and therapeutic potential for EEP against periodontal diseases, improving clinical parameters, reducing gingival bleeding and decreasing bacterial counts of T. forsythensis and P. gingivalis. The subgingival use of EEP represents a promising modality as an adjuvant in periodontal therapy to avoid microbial resistance and other adverse effects.

Jorge Moreno-Fernandez was supported by a Postdoctoral Contract (Contrato Puente) from the University of Granada and Maria Jesus Lisbona-Gonzalez thanks to the doctoral program in clinical medicine and public health., This study investigated the antimicrobial effects of a mouthwash containing propolis and the effect of a propolis paste formulation on dental healing after teeth extraction in patients with periodontal disease. In the mouthwash experience, the population comprised 40 patients, which were divided as follows: the control mouthwash, 0.2% chlorhexidine (v/v) mouthwash, 2% (w/v) propolis mouthwash, and propolis + chlorhexidine mouthwash. The study of the propolis paste comprised a population of 60 patients with periodontal disease, and a total of 120 symmetric tooth extractions were performed. Propolis showed antimicrobial activity by itself, and especially with the chlorhexidine association. Three days after surgery in the teeth treated with control paste, only 13.4% had completely healed; however, with propolis paste, in 90% of the periodontal sockets, healing was complete. In addition, a reduction in Streptococci mutans and Lactobacilli cfu was observed with propolis, and especially with the association of chlorhexidine + propolis. Propolis mouthwash reduced bacterial proliferation, especially in association with chlorhexidine. Propolis paste is a viable alternative for socket healing after dental extraction. The knowledge gained from these findings will provide a foundation for similar propolis therapies in order to improve the healing process after dental surgery., University of Granada

This work was supported by the Regional Government of Andalusia, Excellence Research Project No. P11-AGR-7648. M Garcia Burgos was supported by a fellowship from the Spanish Ministry of Education, Culture and Sport (MECD). J Moreno-Fernandez was supported by a postdoctoral contract (Contrato Puente) from the University of Granada. Funding for open access charge: University of Granada / CBUA., BACKGROUND: Iron deficiency and iron overload can affect the normal functioning of the innate and adaptive immune responses. Fermented milk products may enhance immune functions, but little is known about the effect of fermented milks on modulation of the immune response during iron deficiency anemia and recovery with normal or high dietary iron intake. Eighty male Wistar rats were randomly assigned to a control group fed a standard diet or to an anemic group fed a diet deficit in iron. Control and anemic groups were fed for 30 days with diets based on a fermented goat's or cow's milk product, with normal iron content or iron overload. RESULTS: In general, during anemia recovery lectin and alternative complement pathway activity and lactoferrin decreased, because it improves iron homeostasis, which is critically important in immune system functions. Fermented goat's milk diet enhanced immune function during iron deficiency recovery, suppressed oxidant-induced eotaxin and fractalkine expression due to the concurrent reduction of free radical production and pro-inflammatory cytokines, and decreased monocyte chemoattractant protein-1 and monocyte migration and adhesion. The increase in interferon-γ can confer immunological colonization of gut microbiota and downregulate inflammation. CONCLUSION: Fermented goat's milk consumption enhances immune function, modifying complement pathway activity and decreasing pro-inflammatory cytokines as well as lactoferrin concentration, due to the improvement of iron homeostasis, which is critically important in the normal function of the immune system., Regional Government of Andalusia, Excellence Research Project P11-AGR-7648, Spanish Ministry of Education, Culture and Sport (MECD), University of Granada, University of Granada / CBUA

Experimental and epidemiological evidence has shown that modifications of the intrauterine environment can have deleterious consequences for individuals, expressed as an increased risk of su ering non-communicable pathologies in adult life, which is known as the hypothesis of the early origin of diseases or fetal programming. On the other hand, changes in gene expression patterns through epigenetic modifications can be the basis for long-term maintenance of the e ects of fetal programming. In this sense, epigenetics comprises the study of intrauterine disturbances, which develop diseases in the adult, including celiac disease (CD). In addition, early feeding practices could influence the risk of CD development, such as breastfeeding timing and duration and age of gluten introduction in the diet. Gluten acts as a trigger for CD in genetically predisposed subjects, although approximately 30% of the world population has HLA DQ2 or DQ8, the prevalence of the disease is only 1–3%. It is not known what factors act to modify the risk of disease in genetically at-risk subjects. Taking into account all these considerations, the aim of the current review is to elucidate the role of early programming and the e ect of early nutrition on the development and progression of CD. It is logical that attention has been paid to gluten as a key element in preventing the disease. However, there is no strong evidence in favor of the protective factor of breastfeeding, timing of introduction of gluten during lactation, and the development of CD. Diet, genetic risk, microbiota, and environmental interaction are possible triggers of the change in tolerance to an immune response to gluten, but large-scale cohort studies are needed. Emerging scientific concepts, such as epigenetics, may help us establish the role of these factors., University of Granada

Pablo Mira-Rufino and Jorge Moreno-Fernandez are grateful to the Excellence Ph.D. Program "Nutricion y Ciencias de los Alimentos" from the University of Granada. Jorge Moreno-Fernandez was supported by the fellowship from the Ministry of Education, Culture and Sport (Spain). The authors thank the Fire Department of Granada for their participation in the current study., Bone and energy metabolism are profoundly influenced by exercise. The objective of this study was to determine for the first time whether a short-term supplementation with ubiquinol could have a modulating effect on bone turnover and energy metabolism associated with strenuous exercise. The participants (n= 100 healthy and well-trained firemen) were randomly divided into two groups: ubiquinol group (ubiquinol (200 mg day(-1))) and control group (placebo) for two weeks. The protocol consisted of conducting two identical strenuous exercise tests with a rest period between tests of 24 h. Blood samples were collected before supplementation (basal value) (T1), after supplementation (T2), after the first physical exercise test (T3), after 24 h of rest (T4), and after the second physical exercise test (T5). Parathyroid hormone (PTH), osteocalcin (OC), osteoprotegerin (OPG), osteopontin (OPN), sclerotin (SOST), alkaline phosphatase (AP), adrenocorticotropin (ACTH), insulin, leptin, adrenaline, noradrenaline and peroxisome proliferator activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) were determined. Our protocol increased ACTH, SOST, PTH and OC levels, while it decreased OPN. This protocol also increased adrenaline, noradrenaline and PCG-1 alpha, and decreased insulin. After ubiquinol supplementation, PTH, OC, OPG, alkaline phosphatase, leptin, insulin, noradrenaline and PGC-1 alpha levels increased in the supplemented group compared to the control group after the exercise protocol. Strenuous exercise has a clear effect on energy metabolism and bone turnover. These effects are modulated by ubiquinol supplementation, which especially increases the biomarkers of bone formation during strenuous exercise. In addition, ubiquinol has a beneficial effect on the mobilization of energy sources, fact that it could represent an ergogenic and physiological advantage for skeletal muscles., Ministry of Education, Culture and Sport (Spain)

Background Iron (Fe) plays a crucial role in several fundamental processes, including erythropoiesis, cellular metabolism, and in cardiovascular disease. The aim of this work was to contribute to a better understanding of the physiology of and recovery from Fe deficiency by studying how fermented milk consumption affects vascular biomarkers during Fe repletion. Results The deleterious cardiovascular biomarkers cytokine-induced neutrophil chemoattractant 1, connective tissue growth factor (CTGF), interleukin-6, monocyte chemoattractant protein-1 (MCP-1), inhibitor of tissue plasminogen activator 1 total, metallopeptidase inhibitor 1 (TIMP-1), tumor necrosis factor alpha, vascular endothelial growth factor (VEGF), sE-selectin, and soluble intercellular adhesion molecule 1 (sICAM-1) decreased after fermented goat milk consumption in groups of fed animals either with normal Fe or Fe overload with respect to rats fed with fermented cow milk. The beneficial cardiovascular biomarkers caveolin-1 and adiponectin were higher in both control and anemic rats fed fermented goat milk either with normal Fe or Fe overload with respect to fermented cow milk. Anemia decreased TIMP-1 in rats fed fermented goat milk with Fe overload, whereas there was increased CTGF and MCP-1 in animals fed fermented cow milk with either normal or Fe overload. In addition, Fe overload increased VEGF. Conclusion Fermented goat milk consumption improves hematological status and promotes beneficial metabolic responses, which may attenuate cardiovascular risk factors during anemia recovery and iron overload to lessen the inflammatory response, macrophages activation and atherosclerosis development. © 2018 Society of Chemical Industry.

The aim of this study was to evaluate for the first time the effect of omega-3 LC PUFA supplementation during pregnancy and lactation on bone metabolism in mothers and neonates. 110 pregnant women were divided in two groups: control group (400 mL/day of the control dairy drink); supplemented group (400 mL/day of the fish oil-enriched dairy drink). Plasma bone biomarkers and mineral content in erythrocyte cytosol were assessed. In mothers, DHA supplementation increased OC and OPN levels and decreased IL-6 and TNF-α levels at delivery, increasing PTH levels during lactation. In neonates, DHA supplementation increased ACTH, insulin and leptin, decreasing RANKL and IL-6 in umbilical vein; increased OPG and leptin and diminished TNF-α in umbilical artery; increased OC levels, lowered PTH and TNF-α at birth. DHA supplementation during pregnancy and lactation has beneficial effects on bone turnover in both mother and neonates, representing a non-pharmacological pathway to decrease bone loss.

To date, no studies are available about adipose tissue modifications during anemia recovery; therefore, the aim of this study is to provide detailed information about adipose tissue homeostasis during anemia recovery with fermented milks. Forty male Wistar rats were placed on a pre-experimental period of 40 days, divided in two groups (normal-Fe diet and Fe-deficient diet). Then rats were fed fermented goat or cow milk-based diets with normal-Fe content during 30 days. Ghrelin and adiponectin decreased in both groups of animals fed fermented goat milk, whereas leptin and NEFA increased. UCP-1 decreased in anemic rats fed either fermented milk, and irisin greatly increased in both groups of animals fed fermented goat milk. Fermented goat milk reduces adiposity, inducing leptin elevation and ghrelin reduction. Conversely, plasma adiponectin concentrations decreased in animals fed fermented goat milk, showing an inverse correlation with NEFA, an important marker of lipid mobilization, indicating increased lipolysis. Irisin up-regulation in animals fed fermented goat milk contributes to a favorable metabolic profile and the browning of adipose tissue during anemia recovery.

Strenuous exercise (any activity that expends six metabolic equivalents per minute or more causing sensations of fatigue and exhaustion to occur, inducing deleterious effects, affecting negatively different cells), induces muscle damage and hematological changes associated with high production of pro-inflammatory mediators related to muscle damage and sports anemia. The objective of this study was to determine whether short-term oral ubiquinol supplementation can prevent accumulation of inflammatory mediators and hematological impairment associated to strenuous exercise. For this purpose, 100 healthy and well-trained firemen were classified in two groups: Ubiquinol (experimental group), and placebo group (control). The protocol was two identical strenuous exercise tests with rest period between tests of 24 h. Blood samples were collected before supplementation (basal value) (T1), after supplementation (T2), after first physical exercise test (T3), after 24 h of rest (T4), and after second physical exercise test (T5). Hematological parameters, pro- and anti-inflammatory cytokines and growth factors were measured. Red blood cells (RBC), hematocrit, hemoglobin, VEGF, NO, EGF, IL-1ra, and IL-10 increased in the ubiquinol group while IL-1, IL-8, and MCP-1 decreased. Ubiquinol supplementation during high intensity exercise could modulate inflammatory signaling, expression of pro-inflammatory, and increasing some anti-inflammatory cytokines. During exercise, RBC, hemoglobin, hematocrit, VEGF, and EGF increased in ubiquinol group, revealing a possible pro-angiogenic effect, improving oxygen supply and exerting a possible protective effect on other physiological alterations.

Early programming is the adaptation process by which nutrition and environmental factors alter development pathways during prenatal growth, inducing changes in postnatal metabolism and diseases. The aim of this narrative review, is evaluating the current knowledge in the scientific literature on the e ects of nutrition, environmental factors, physical activity and sleep on development pathways. If in utero adaptations were incorrect, this would cause a mismatch between prenatal programming and adulthood. Adequate caloric intake, protein, mineral, vitamin, and long-chain fatty acids, have been noted for their relevance in the o spring brain functions and behavior. Fetus undernutrition/malnutrition causes a delay in growth and have detrimental e ects on the development and subsequent functioning of the organs. Pregnancy is a particularly vulnerable period for the development of food preferences and for modifications in the emotional response. Maternal obesity increases the risk of developing perinatal complications and delivery by cesarean section and has long-term implications in the development of metabolic diseases. Physical exercise during pregnancy contributes to overall improved health post-partum. It is also interesting to highlight the relevance of sleep problems during pregnancy, which influence adequate growth and fetal development. Taking into account these considerations, we conclude that nutrition and metabolic factors during early life play a key role of health promotion and public health nutrition programs worldwide to improve the health of the o spring and the health costs of hospitalization., University of Granada

Iron is an essential micronutrient that is involved in many functions in humans, as it plays a critical role in the growth and development of the central nervous system, among others. Premature and low birth weight infants have higher iron requirements due to increased postnatal growth compared to that of term infants and are, therefore, susceptible to a higher risk of developing iron deficiency or iron deficiency anemia. Notwithstanding, excess iron could affect organ development during the postnatal period, particularly in premature infants that have an immature and undeveloped antioxidant system. It is important, therefore, to perform a review and analyze the effects of iron status on the growth of premature infants. This is a transversal descriptive study of retrieved reports in the scientific literature by a systematic technique. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were adapted for the review strategy. The inclusion criteria for the studies were made using the PICO (population, intervention, comparison, outcome) model. Consequently, the systematic reviews that included studies published between 2008–2018 were evaluated based on the impact of iron status on parameters of growth and development in preterm infants.

Studies about Coenzyme Q10 (CoQ10 ) supplementation on strenuous exercise are scarce, especially those related with oxidative stress associated with physical activity and virtually nonexistent with the reduced form, Ubiquinol. The objective of this study was to determine, for the first time, whether a short-term supplementation with Ubiquinol can prevent oxidative stress associated to strenuous exercise. The participants (n = 100 healthy and well trained, but not on an elite level) were classified in two groups: Ubiquinol (experimental group), and placebo group (control). The protocol consisted of conducting two identical strenuous exercise tests with a rest period between tests of 24 h. Blood and urine samples were collected from the participants before supplementation (basal value) (T1), after supplementation (2 weeks) (T2), after first physical exercise test (T3), after 24 h of rest (T4), and after second physical exercise test (T5).The increase observed in the lactate, isoprostanes, DNA damage, and hydroperoxide levels reveals the severity of the oxidative damage induced by the exercise. There was a reduction in the isoprostanes, 8-OHdG, oxidized LDL, and hydroperoxydes in the supplemented Ubiquinol group, an increase in total antioxidant status, fat soluble antioxidant (both plasma and membrane), and CAT activity. Also, NO in the Ubiquinol-supplemented group was maintained within a narrow range. Oxidative stress induced by strenuous exercise is accumulative and increases transiently in subsequent sessions of physical activity. A short-term supplementation (2 weeks) with Ubiquinol (200 mg/day) before strenuous exercise, decreases oxidative stress and increases plasma NO, fact that could improve endothelial function, energetic substrate supply, and muscle recovery after strenuous exercise. © 2016 BioFactors, 42(6):612-622, 2016.

Oxidative stress is a harmful factor for male reproductive function, and a major cause of infertility. On the other hand, fermented goat milk has positive effects on anemia recovery and mineral metabolism. This study evaluated the effect of feeding rats with fermented milks during anaemia recovery on molecular mechanisms linked to oxidative stress and inflammatory signalling in rats reproductive system. Forty male Wistar rats were placed on a pre-experimental period of 40 days (control group, receiving normal-Fe diet and Fe-deficient group, receiving low-Fe diet). Lately, rats were fed with fermented goat or cow milk-based diets during 30 days. After feeding the fermented milks, Total antioxidant status (TAS) and non-esterified fatty acids (NEFA) increased and 8-hydroxy-2’-deoxyguanosine (8-OHdG), 15-F2t-isoprostanes and thiobarbituric acid reactive substances (TBARS) decreased in testis. DNA oxidative damage in testis germ cells was lower with fermented goat milk. Fermented goat milk reduced IL-6 and TNF-α in control animals, increasing INF-γ in control and anaemic rats. NRF2 and PGC-1α protein levels increased in testis after fermented goat milk consumption in control and anaemic rats. Fermented goat milk also increased TAS and decreased oxidative damage, protecting the main testis cell bioconstituents (lipids, proteins, DNA, prostaglandins) from oxidative damage and reduced inflammatory activity, preventing injuries to testis germinal epithelium. Fermented goat milk enhanced lipolysis, fatty acids degradation and immune response, attenuating inflammatory signalling, representing a positive growth advantage for testicular cells., Jorge Moreno-Fernandez was supported by fellowship from the Ministry of Education, Culture and Sport (Spain) and is grateful to the Excellence Ph.D. Program “Nutrición y Ciencias de los Alimentos” from the University of Granada. This study was supported by Andalusian Government, Excellence Research Project No. P11-AGR-7648.

Celiac disease (CD) is a multifactorial, autoimmune, gluten-sensitive inflammatory disorder of the small intestine. Taking into account the pathogenesis of CD, a strict gluten-free diet (GFD) is the only treatment able to restore epithelium integrity and eliminate complications. The current study was designed to assess whether the use of a GFD is sufficient for maintaining a correct oxidative/antioxidant balance and ameliorating the evoked inflammatory signaling in young patients with CD. The study covered 80 children, aged between 7 and 18 years, attending the Gastroenterology Service of the Gastroenterology, Hepatology and Child Nutrition Service from the Virgen de las Nieves Hospital in Granada. Children with CD diagnosed were included in the celiac group who followed a strict GFD for 2 years (n = 40) and the control group (n = 40) included healthy children, with negative serological screening. Soluble superoxide dismutase 1 and 2, total antioxidant status, 8-hydroxy-2′-deoxyguanosine, cortisol, melatonin and inflammatory parameters in plasma, 15-F2t-isoprostanes in urine, and DNA breaks in peripheral blood lymphocytes were analysed. No differences were found in oxidative stress between CD patients and controls; however, IFN-γ, IL-1α, IP-10 and TNF-β were higher in the CD patients. VEGF was also higher than in the control group. The GFD in the CD patients is enough to reduce the oxidative stress; however, in the case of the inflammatory signaling, the initial exposure to gluten prior to stablish the GFD is strong enough to induce an inflammatory state which is maintained (even when consuming the GFD); meanwhile the increase in VEGF recorded in the CD group could be a compensatory mechanism to restore the damaged mucosa and duodenal villous atrophy, due to its role in endothelial activation and generation of new functional and stable vascular networks.

Objectives: Since Selenium (Se) forms part of glutathione peroxidase (GPx), which appears to have a dual role in Metabolic Syndrome (MS), this study evaluates the implication of Se in the transmission of this pathology to the progeny. Methods: Se body distribution, glucose, triglycerides, cholesterol, insulin and metabolic hormones [glucagon, leptin, gastric inhibitory polypeptide (GIP), and triiodothyronine (T3)], growth factors, receptor activator of nuclear factor kappa-B ligand (RANK-L) and osteopontin, as well as oxidative hepatic balance in the offspring of dams exposed to a fructose-rich diet (65%) with normal Se content (0.01 ppm) during gestation and lactation, were measured according to sex. Results: Fructose pups had lower body weight; however, male pups had a lower body mass index and growth indicators in serum. Fructose pups, especially females, had lower levels of serum insulin and HOMA-IR. With regard to Se homeostasis, fructose pups presented a depletion of Se in heart and muscle, and repletion in kidneys, pancreas and thyroid, although only female pups showed a repletion of Se in the liver. Fructose pups presented lower superoxide dismutase activity and only female fructose pups had higher GPx activity, which provoked hepatic oxidation. Conclusions: Se balance and Se tissue deposits in MS pups during lactation are altered by gender. This difference is focused on hepatic Se deposits that affect GPx activity, which could be related to a disruption in the insulin-signaling cascade in females. Furthermore, although female fructose pups had greater metabolic disorders, only the males’ growth and development were affected. Particularly relevant is the depletion of Se found in the heart of fructose pups, as this element is essential for correct heart function.

The effect of maternal DHA supplementation on expression of key genes and proteins involved in Fe metabolism and mineral placenta content was evaluated for the first time. One hundred and ten pregnant women were randomly assigned to one of the groups: control (n = 54, 400 ml/day of the control dairy drink; DHA-supplemented (n = 56, 400 ml/day of the DHA-enriched dairy drink). Placenta DMT1, FPN1, TfR1 and Hamp1 mRNA and protein expressions were analysed. Hepcidin concentration in the mother and umbilical cord and placenta mineral content were assessed. DMT1, FPN1, TfR1 and Hamp1 gene expressions together with serum hepcidin increased in umbilical cord and artery of the DHA-supplemented group. In this group, Fe concentration increased in plasma, umbilical cord vein and artery. Ca concentrations raised in umbilical cord vein and artery, Cu, V and Mn levels. Docosahexaenoic acid (DHA) supplementation improved transplacental Fe homeostasis, enhancing Fe transfer and boosting neonates Fe stores at delivery.

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.

High- and low- Se diets received by dams during gestation and lactation are related to insulin resistance in their pups. High-Se diet leads to an increase in serum insulin levels, which does not function properly, and an anabolic process. Low-Se diet is related to very low insulin values and an extreme catabolic energy imbalance. Selenoproteins have been implicated directly in the general endocrine regulation of appetite and energy homeostasis. To obtain information concerning how Se intake by dams is involved in regulating endocrine energy balance in progeny, three experimental groups of dam rats were used: control (Se: 0.1 ppm), Se-supplemented (Se: 0.5 ppm) and Se-deficient (Se: 0.01 ppm). At the end of lactation (21d old), the pups' appetite profile, Se levels, peptides from gastrointestinal tract (including pancreas), leptin, thyroid hormones, skeletal growth markers and cytokines in serum were measured. Low-Se diet leads to severe growth retardation, underdeveloped glands, a non-functional pancreas, non-operative high serum leptin levels and low GIT-anorexigenic signals. High-Se diet leads to non-operative high insulin secretion, obesity, inflammation and low leptin levels. These results point to Se as an important marker and a possible dietary supplementation treatment for gestating and lactating mothers in order to avoid metabolic disorders such as gestational diabetes or intrauterine growth retardation which could affect their progeny's future health in adulthood.

Celiac disease (CD) is a multisystemic disorder with di erent clinical expressions, from malabsorption with diarrhea, anemia, and nutritional compromise to extraintestinal manifestations. Anemia might be the only clinical expression of the disease, and iron deficiency anemia is considered one of the most frequent extraintestinal clinical manifestations of CD. Therefore, CD should be suspected in the presence of anemia without a known etiology. Assessment of tissue anti-transglutaminase and anti-endomysial antibodies are indicated in these cases and, if positive, digestive endoscopy and intestinal biopsy should be performed. Anemia in CD has a multifactorial pathogenesis and, although it is frequently a consequence of iron deficiency, it can be caused by deficiencies of folate or vitamin B12, or by blood loss or by its association with inflammatory bowel disease (IBD) or other associated diseases. The association between CD and IBD should be considered during anemia treatment in patients with IBD, because the similarity of symptoms could delay the diagnosis. Vitamin B12 deficiency is common in CD and may be responsible for anemia and peripheral myeloneuropathy. Folate deficiency is a well-known cause of anemia in adults, but there is little information in children with CD; it is still unknown if anemia is a symptom of the most typical CD in adult patients either by predisposition due to the fact of age or because biochemical and clinical manifestations take longer to appear.

Iron deficiency anemia (IDA) is one of the most prevalent nutritional deficiencies worldwide. Iron plays critical roles in nervous system development and cognition. Despite the known detrimental consequences of IDA on cognition, available studies do not provide molecular mechanisms elucidating the role of iron in brain functions during iron deficiency and recovery with dairy components. In this study, 100 male Wistar rats were placed on a pre-experimental period of 40 days and randomly divided in two groups: a control group receiving a normal-Fe diet, (45 mg/kg), and an Fe-deficient group receiving a low-Fe diet (5 mg/kg). At day 40, 10 rats per group were sacrificed to anemia control, and 80 rats were divided into eight experimental groups fed with fermented goat or cow milk-based diets, with normal Fe content or Fe overload (450 mg/kg) for 30 days. IDA decreased most of the parameters related to brain molecular functions, namely dopamine, irisin, MAO-A, oxytocin, &beta, endorphin, and &alpha, MSH, while it increased synaptophysin. These alterations result in an impairment of brain molecular functions. In general, during anemia recovery, fermented goat milk diet consumption increased dopamine, oxytocin, serotonin, synaptophysin, and &alpha, MSH, and decreased MAO-A and MAO-B, suggesting a potential neuroprotective effect in brain functions, which could enhance brain molecular functions.

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.

The study was designed to assess the effect of several Fe amounts and sources on haematological parameters, DNA, lipid and protein oxidative damage during the course of Fe-deficiency anaemia recovery. Peripheral DNA damage was assessed using an alkaline comet assay. The brain, liver, erythrocyte and duodenal mucosa lipid peroxidation and protein damage were assessed in control and anaemic rats after Fe repletion with three different sources (FeSO4, haem Fe, and FeSO4 + haem Fe) and amounts (45, 12, and 31 mg Fe/kg diet) of Fe: F diet, H diet or C diet, respectively. After supplying the diets, the haematological parameters studied were recovered; being remarkable is the haemoglobin increase. The DNA damage was lower in rats with the H diet, as revealed by the percentage of DNA in head, tail and Olive tail moment compared in rats with the F (P

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 400 mL/day of a fish oil-enriched dairy drink [320 mg docosahexaenoic acid (DHA) + 72 mg eicoapentaenoic acid] (FO group, n = 24) or to a control group receiving 400 mL/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”.

Oxidative stress results from an imbalance between the formation and neutralization of reactive oxygen species (ROS), and it is imposed on cells because of one or more of the following factors: an increase in oxidant generation, a decrease in antioxidant protection, or a failure to repair oxidative damage. There is controversy about the susceptibility of cells to lipid peroxidation in iron deficiency anemia (IDA)—some investigators have claimed there is no difference in lipid peroxidation among patients with IDA compared with controls, but others have reported that among patients with IDA oxidants are increased and antioxidants decreased, so the oxidative/antioxidative balance is shifted toward the oxidative side. This apparent discrepancy may be due to different concentrations of ROS and antioxidant enzymes in the tissues studied, the subjects of the study, the severity of the iron deficiency, and the methods used for the assessment of the oxidative stress. However, in humans, where the degree of iron deficiency is not very high, it is accepted that iron deficiency increases oxidative stress, a fact that can also be attributed to the repletion process with several sources of iron. Several authors have reported increased lipid peroxidation products in patients with iron-deficiency anemia, which may be attributed to overproduction of ROS and a deficiency of antioxidant defense. Decreased superoxide dismutase (SOD) activity in iron-deficiency anemia may be linked to increased oxidative stress, because it is well known that ROS inhibits SOD activity. On the other hand, goat milk has beneficial effects, reducing oxidative stress and protecting cell bioconstituents from free radicals. Caprine milk alters the activities of enzymes that improve the total antioxidative defense capacity of the organism, a fact that limits the oxidative damage to the main biomolecules (lipids, protein DNA, and prostaglandins).

There is a growing body of evidence from animal research, epidemiologic, and clinical studies indicating an association between osteopenia and anemia. Iron (Fe) intake is directly correlated with mineral bone density, and iron deficiency diminishes the mineral bone content, the bone mass, and mechanical resistance. There is also an association of hemoglobin levels with the cortical bone mineralization and density. Several diseases characterized by low-hemoglobin levels or iron-deficiency anemia have been associated with an increased risk of bone loss or osteoporosis. In fact, pernicious anemia is directly correlated with increased risk of osteoporotic fractures. Iron deficiency diminishes bone matrix formation, reducing the amount of procollagen type I N-terminal propeptide released to the serum under these conditions. Bone resorption process increases in iron deficiency as shown by the increase of serum parathyroid hormone, tartrate-resistant acid phosphatase, and levels of degradation products from C-terminal telopeptides of type I collagen. In addition, mineralization process is also affected by iron deficiency, because calcium and phosphorus content in femur decreases markedly, due to the increase in parathyroid hormone and cortisol induced by iron deficiency. Osteoblast function and bone formation are strongly oxygen dependent. Hypoxic condition (a consequence from decreased oxygen delivery in iron-deficiency anemia) diminishes bone formation. The inhibitory effects of hypoxia are due to decreased osteoblast proliferation and differentiation. In addition, hypoxia stimulates osteoclast activity in favor of pathological resorption. In conclusion, iron-deficiency anemia has a significant impact upon bone, affecting bone mineralization, decreasing the matrix formation, and increasing bone resorption, therefore it is of great interest to assess bone status when there is iron-deficiency anemia. On the other hand, habitual goat milk consumption improves mineral metabolism and increases levels of the biomarker of bone formation N-terminal propeptides of type I procollagen and diminishes parathyroid hormone, which positively affects bone mineralization and turnover.

The beneficial effects of regular, nonexhaustive physical exercise are well-known, however, these beneficial effects are lost with strenuous exercise. High-intensity exercise induces inflammatory reactions together with high production of free radicals, muscle damage, and subsequent inflammation indicated by muscle soreness and swelling, prolonged loss of muscle function, and the leakage of muscle proteins, such as creatine kinase and myoglobin, into the circulation. The pineal hormone, melatonin (N-acetyl-5-methoxytryptamine), is a potent, endogenously produced and diet-derived free radical scavenger and broad-spectrum antioxidant, consequently, it might have positive effects on the recovery following the exercise session. Among other effects, several studies have shown that oral supplementation of melatonin during high-intensity exercise is efficient in reducing the degree of oxidative stress (decreasing lipid peroxidation, with a significant increase of antioxidant enzymes activity), which lead to the maintenance of the cell integrity and the reduction of secondary tissue damage. Data also indicate that melatonin has potent protective effects, preventing over-expression of pro-inflammatory mediators and inhibiting the effects of several pro-inflammatory cytokines. The aim of this chapter is to review the most relevant studies focused on the effect of melatonin on diverse negative aspects associated with strenuous exercise, such as oxidative stress or the inflammatory signaling, in human, animals, and in vitro assays. Melatonin supplementation can decrease muscle damage through modulation of oxidative stress, inflammatory signaling, improving recovery, and performance efficiency associated to the physical challenge.

Calcium-fortified foods, especially milk and dairy products are recommended to be consumed daily for groups in risk of nutritional deficiency, including children, young adults, menopausal women, pregnant women and the elderly, however Ca-supplementation promotes gallstone formation because Ca is a nucleating factor. The objective of the current study was to assess the influence of cow or goat milk-based diets, either normal or Ca-supplemented, on bile composition, biochemical parameters and hepatic antioxidant status. Weanling male rats were randomly divided into six groups, fed standard, goat or cow milk-based diets, either with normal Ca content (5·0 g/kg), or Ca-supplemented (10·0 g/kg), for 2 weeks. Bile cholesterol concentration and output was higher in rats fed goat milk in comparison with those fed with standard and cow-milk-based diet. Ca-supplementation increased lithogenic index with the standard and cow-milk based diets, this change was not observed with the goat milk diet. Activities of plasma transaminases were also lower in the animals fed Ca-supplemented goat milk, in comparison with the other diets assayed. In general, Ca-supplement in the diet led to an increase in the hepatic oxidative damage, with an increase in the activities of all the antioxidant enzymes studied in the standard and cow milk diet, but not with goat milk. The habitual consumption of goat milk has positive effects on the plasma lipid profile, biliary composition and hepatic antioxidant defence. In addition, under our experimental conditions, Ca-supplementation of this type of milk does not increase the lithogenic index, or hepatic oxidative damage.

Strenuous exercise induces muscle damage due to a highly increased generation of free radicals and inflammatory response and therefore, in this type of exercise, it is important to reduce both oxidative stress and inflammation, at least their negative aspects. The purpose of this study was investigate, for the first time, whether a purified, standard water-soluble fraction obtained from Phlebodium decamanum could reduce the over-expression of inflammation and oxidative stress induced by strenuous exercise. The physical test consisted of a constant run that combined several degrees of high effort (mountain run and ultra-endurance), in permanent climbing. Biochemical parameters, oxidative stress and inflammatory mediators were assessed. The results showed that oral supplementation of P. decumanum during high-intensity exercise effectively reduces the degree of oxidative stress (decreased 8-hydroxy-2'-deoxyguanosine and isoprostanes generation, increased antioxidant enzyme activities in erythrocyte and total antioxidant status in plasma). The data obtained also indicate that this supplementation is efficient in reducing the inflammatory response through the decrease of TNF-α and increase of sTNF-RII, but kept the levels of IL-6 and IL-1ra. In conclusion, oral supplementation of P. decamanum extract during high-intensity exercise effectively reduces the degree of oxidative stress and has anti-inflammatory protective effects, preventing the over-expression of TNF-α but keeping the levels and effects of IL-6. These findings provide a basis for similar Phlebodium supplementation for both professional and amateur athletes performing strenuous exercise in order to reduce the undesirable effects of the oxidative stress and inflammation signalling elicited during high-intensity exercise.

The role of iron (Fe) in bone formation and disease have not received much attention, a fact that is interesting given the known biochemical role that this mineral has upon collagen maturation together with the high prevalence of Fe-deficiency anaemia worldwide.To investigate the changes in bone formation, resorption and mineral content in developing rats with induced nutritional Fe-deficiency anaemia.Thirty male Wistar rats were divided into two groups, a control group receiving AIN-93G diet with normal-Fe content and an anaemic group receiving AIN-93G diet with low-Fe content for 40 days. Both diets were prepared with an adequate calcium (Ca) and phosphorus (P) content. The most representative serum bone turnover biomarkers and femur and sternum calcium and phosphorus content, together with sternum Fe content were determined in both experimental groups.In anaemic rats, bone matrix formation diminished as revealed by the lower amount of procollagen type I N-terminal propeptide. Bone resorption process increased in Fe deficiency as shown by the increase of serum parathyroid hormone, tartrate-resistant acid phosphatase and levels of degradation products from C-terminal telopeptides of type I collagen released to the serum. In addition, mineralization process was affected by Fe deficiency, because Ca and P content in femur decreased markedly.Fe-deficiency anaemia had a significant impact upon bone, affecting bone mineralization, decreasing the matrix formation and increasing bone resorption, therefore it is of great interest to assess bone status in situation of Fe-deficiency anaemia.

Strenuous exercise induces inflammatory reactions together with high production of free radicals and subsequent muscle damage. This study was designed to investigate for the first time and simultaneously whether over-expression of inflammatory mediators, oxidative stress, and alterations in biochemical parameters induced by acute exercise could be prevented by melatonin. This indoleamine is a potent, endogenously produced free radical scavenger and a broad-spectrum antioxidant; consequently, it might have positive effects on the recovery following an exercise session. The participants were classified into two groups: melatonin-treated men (MG) and placebo-treated individuals (controls group, CG). The physical test consisted in a constant run that combined several degrees of high effort (mountain run and ultra-endurance). The total distance of the run was 50 km with almost 2800 m of ramp in permanent climbing and very changeable climatic conditions. Exercise was associated with a significant increase in TNF-α, IL-6, IL-1ra (in blood), and also an increase in 8-hydroxy-2'-deoxyguanosine (8-OHdG) and isoprostane levels (in urine), and indicated the degree of oxidative stress and inflammation induced. Oral supplementation of melatonin during high-intensity exercise proved efficient in reducing the degree of oxidative stress (lower levels of lipid peroxidation, with a significant increase in antioxidative enzyme activities); this would lead to the maintenance of the cellular integrity and reduce secondary tissue damage. Data obtained also indicate that melatonin has potent protective effects, by preventing over-expression of pro-inflammatory mediators and inhibiting the effects of several pro-inflammatory cytokines. In summary, melatonin supplementation before strenuous exercise reduced muscle damage through modulation of oxidative stress and inflammation signaling associated with this physical challenge.

Although dietary iron is a determinant of iron status in animals, body fat mass has been reported to have an inverse association with iron status in human studies. The goal of this study was to determine the relationship between Fe homeostasis, body composition, energy expenditure and neuroendocrine regulators for severe Fe-deficiency anaemia. Forty male Wistar albino rats recently weaned were divided at random into two groups: the control group was fed the basal diet, AIN-93G diet (normal-Fe) and the anaemic group received a low-Fe diet for 40 days. Neuroendocrine parameters that regulate basal metabolism and appetite (thyroid hormones, ghrelin, glucose-dependent insulinotropic polypeptide (GIP), glucagon, insulin, adrenocorticotropic hormone and corticosterone), body composition, respiratory volumes, energy expenditure, haematological and biochemical were assessed. Total body fat was lower, whereas lean mass, free and total water were higher in the anemic group. O2 consumption, CO2 production, energy expenditure (EE) and respiratory quotient (RQ) were lower in the Fe-deficient animals. Triiodothyronine and thyroxine hormones decreased, while thyroid-stimulating hormone increased in the anemic group. Circulating levels of ghrelin were lower in the anemic group, while GIP, glucagon, insulin, corticosterone and adrenocorticotropic hormone levels were higher. Fe-deficiency impairs weight gain in the rats, with marked reductions in lean mass and body fat, indicating lower energy stores.

The effect of cow or goat milk-based diets, either normal or Fe-overloaded, on DNA stability was studied in control and anaemic rats for 30 or 50 days of chronic Fe repletion. DNA damage was assessed using the alkaline comet assay. Background DNA damage in lymphocytes of peripheral blood was much lower in control and anaemic rats, given the normal or Fe-overloaded goat milk-based diet after 30 and 50 days versus cow milk-based diet. Chronic Fe-overload had no adverse effect on DNA stability in control and anaemic fed the goat milk-based diet versus the same diet with normal-Fe content at the end of the study. The quality of goat milk fat, together with the high levels of bioavailable Mg and Zn may be responsible for its protective effect on DNA of peripheral blood lymphocytes under the different experimental conditions, even during chronic Fe-overload.

In this study, we set out to perform a comparative evaluation of variations in body weight and volume between two groups of women, one young adult and the other perimenopausal, each of which followed a specific weight loss program for the same period of time. The evaluation was based on the weight and volume data obtained from a clinical and anthropometric study. From the anthropometric values obtained, we conclude that in both groups of women, the diet followed was found to be effective in reducing weight and volume, but with respect to time, the weight loss was more noticeable among the younger women, while among the menopausal women it took place more slowly. The difference between the two groups might be explained by diverse hormonal effects, such that metabolism (and therefore caloric expenditure) is higher among the younger women.

Despite the crucial roles of duodenal cytochrome b (Dcytb), divalent metal transporter 1 (DMT1), ferritin light chain (Ftl1), ferroportin 1 (FPN1), transferrin receptor 1 (TfR1), and hepcidin antimicrobial peptide (Hamp) in Fe metabolism, no studies have investigated the modulations of these genes during Fe repletion with fermented milks. Analysis included Fe status markers and gene and protein expression in enterocytes of control and anemic animals fed fermented milks. Fermented goat's milk up-regulated enterocyte Dcytb, DMT1, FPN1, and Ftl1 and down-regulated TfR1 and Hamp gene expression in control and anemic animals. Anemia decreased Dcytb, DMT1, and Ftl1 in animals fed fermented cow's milk and up-regulated TfR1 and Hamp expression. Fe overload down-regulated Dcytb and TfR1 in animals fed fermented cow's milk and up-regulated DMT1 and FPN1 gene expression. Fermented goat's milk increased expression of duodenal Dcytb, DMT1, and FPN1 and decreased Hamp and TfR1, improving Fe metabolism during anemia recovery.

Gender is a crucial determinant of life span, but little is known about gender differences in free radical homeostasis and inflammatory signaling. The aim of the study was to determine gender-related differences concerning oxidative stress and inflammatory signaling of healthy neonates and mothers. Fifty-six mothers with normal gestational course and spontaneous delivery were selected. Blood samples were collected from the mother (at the beginning of delivery and start of expulsive period) and from neonate (from umbilical cord vein and artery). The mothers of girls featured a higher total antioxidant status and lower plasma hydroperoxides than the mother of boys. Regarding the neonates, the girls featured a higher total antioxidant status and lower plasma membrane hydroperoxides in umbilical cord artery together with higher catalase, glutathione peroxidase, and superoxide dismutase activities. Lower levels of interleukin 6, tumor necrosis factor alpha, and prostaglandin E2 were observed in the mothers of girls and higher level of soluble tumor necrosis factor receptor II. In the neonates, lower levels of interleukin 6 and tumor necrosis factor alpha were observed in umbilical artery and higher soluble tumor necrosis factor receptor II in umbilical cord vein and artery of girls. An association between gender, oxidative stress, and inflammation signaling exists, leading to a renewed interest in the neonate’s sex as a potential risk factor to several alterations.

Anaemia is associated with fatigue and diminished muscular oxygenation, which may affect skeletal muscle (SM). No studies are available about the SM modifications during anaemia recovery; therefore, the aim of this study is to study SM homeostasis during anaemia recovery with fermented milks. Forty male Wistar rats were placed on a pre-experimental period of 40 days, divided in two groups (control group receiving normal-Fe diet and Fe-deficient group receiving low-Fe diet). Lately, rats were fed with fermented goat or cow milk-based diets, with normal-Fe content during 30 days. After feeding the fermented milks, leptin, adiponectin, non-esterified fatty acids (NEFA) and protein expression (UCP1, PepT1 and irisin) within the SM were assessed. Adiponectin decreased in both groups of animals fed fermented goat milk, while leptin and NEFA increased. UCP1 protein expression increased in control and anaemic animals fed fermented goat milk. UCP1 also increased in both group of anaemic animals fed either fermented cow or goat milk in comparison with their controls. Irisin increased in both group of animals fed fermented goat milk. Finally, PepT1 also showed an increased expression in control and anaemic rats fed fermented goat milk and the anaemia also induced an over-expression of this transporter in animals fed either fermented cow or goat milk. Fermented goat milk consumption during anaemia recovery diminishes adiposity depots and enhances lipolysis, increasing UCP1, PepT1 and irisin protein expression, featuring an ergogenic effect in the SM which is an important endocrine regulator of body metabolism.

Bone is a metabolically active tissue that undergoes continuous remodeling to cope with the body’s Ca and P requirements and to repair microscopic damage in a dynamic process where osteoblasts are responsible for bone formation and osteoclasts for its resorption. Dietary fat has a clear influence on bone health. Long-chain polyunsaturated fatty acids (LC-PUFAs), especially the omega-3 (ω-3) fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are beneficial for bone metabolism. Several studies have reported that LC-PUFAs can increase bone formation, affecting peak bone mass in adolescents and reducing bone loss, because LC-PUFAs reduce inflammatory cytokines, increases calcium absorption, and enhances skeletal calcium levels. This chapter summarizes the role of LC-PUFA, especially the ω-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid, on bone health and turnover.

This study investigates the effects of consumption of dietary caprine and bovine milk on Ca and P bioavailability, their distribution in different target organs, and parathormone (PTH) and corticosterone levels in rats with induced nutritional ferropenic anaemia (NFA). NFA increased the absorption of Ca and P, while their deposition in the femur was significantly lower, resulting in a significant degree of bone demineralization. Furthermore, anaemia led to an increased concentration in PTH and corticosterone in serum. Dietary caprine milk had a beneficial effect on Ca and P bioavailability in NFA, increasing the digestive and metabolic utilization of these elements and their deposits in the corresponding target organs, especially in the femur, together with lower levels of serum PTH. The opposite effect was observed for bovine milk diet. The consumption of caprine milk appears able to restore, at least in part, the impaired Ca and P metabolism and bone demineralization observed in rats with NFA.

Fe overload is a common consequence of the anaemia treatment, increasing the oxidative stress and promoting the accumulation of damaged biomolecules, with the subsequently impairment of cell functions. Oxidative stress and the role of folic acid preventing free radical damage have been extensively studied; nevertheless, no studies are available about the influence of folic acid-supplemented goat milk consumption on the oxidative stress-mediated damage.The objective of the present study was to assess the influence of folic acid supplementation of goat milk- or cow milk-based diets, after Fe-overload treatment to palliate anaemia, on oxidative stress-mediated biomolecular damage in the liver, brain, erythrocytes, duodenal mucosa and plasma.Control and anaemic rats were fed goat milk- or cow milk-based diets, either with normal Fe or Fe overload (450 mg/kg), and normal folic acid (2 mg/kg) or folic acid supplemented (40 mg/kg) for 30 days.During chronic Fe repletion, background DNA damage was significantly lower in anaemic rats fed folic acid-supplemented goat milk-based diet, as revealed by tail DNA (%), and folic acid-supplemented goat milk also had a beneficial effect, reducing the extent of lipid peroxidation in liver, plasma, erythrocytes and especially in brain and duodenal mucosa. Furthermore, protein oxidative damage was lower in anaemic rat duodenal mucosa for all goat milk-based diets.Folic acid supplement in goat milk avoids the undesirable effects of Fe overload during anaemia recovery in all the tissues studied, especially in the liver and duodenal mucosa, which are the tissues with higher exposition to dietary Fe.

Background. Evidence has shown that long-chain polyunsaturated fatty acids (LCPUFA), especially theω-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are beneficial for bone health and turnover.Objectives. This review summarizes findings from bothin vivoandin vitrostudies and the effects of LC PUFA on bone metabolism, as well as the relationship with the oxidative stress, the inflammatory process, and obesity.Results. Some studies in humans indicate that LCPUFA can increase bone formation, affect peak bone mass in adolescents, and reduce bone loss. However, the cellular mechanisms of action of the LCPUFA are complex and involve modulation of fatty acid metabolites such as prostaglandins, resolvins and protectins, several signaling pathways, cytokines, and growth factors, although in certain aspects there is still some controversy. LCPUFA affect receptor activator of nuclear factorκβ(RANK), a receptor found on the osteoclast, causing bone resorption, which controls osteoclast formation.Conclusions. Since fatty acids are an endogenous source of reactive oxygen species, free radicals alter the process of bone turnover; however, although there are clinical evidences linking bone metabolism and dietary lipids, more clinical trials are necessary to prove whetherω-3 PUFA supplementation plays a major role in bone health.

There is controversy about fish-oil supplementation and oxidative damage. This ambiguity should be explored to elucidate its role as modulator of oxidative stress, especially during gestation and postnatal life. This is the objective of this study. One hundred ten pregnant women were divided in two groups: control group CT (400 mL/day of the control dairy drink); supplemented group FO (400 mL/day of the fish oil-enriched dairy drink (±400-mg EPA-DHA/day)). Different biomarkers of oxidative damage were determined in the mother's at enrolment, at delivery and at 2.5 and 4 months postpartum and newborns at delivery and at 2.5 months postpartum. Omega-3 LC-PUFA supplementation during pregnancy and lactation decreased plasma hydroperoxides especially in newborn at delivery (P = 0.001) and 2.5 months (P = 0.006), increased superoxide dismutase (SOD) and catalase (CAT) in mothers at delivery (P = 0.024 (SOD)) and after 2.5 months (P = 0.040 (CAT)) and in newborns at 2.5 months (P = 0.035 (SOD); P = 0.021 (CAT)). Also, supplementation increased α-tocoferol in mothers at 2.5 months (P = 0.030) and in umbilical cord artery (P = 0.039). Higher levels of CoQ10 were found in mothers at delivery (P = 0.039) as well as in umbilical cord vein (P = 0.024) and artery (P = 0.036). Our supplementation prevents the oxidative stress in the mother and neonate during the first months of postnatal life, being a potential preventive nutritional strategy to prevent functional alterations associated with oxidative stress that have an important repercussion for the neonate development in the early postnatal life.

The BMP/SMAD4 pathway has major effects on liver hepcidin levels. Bone morphogenetic protein-binding endothelial cell precursor-derived regulator (Bmper), a known regulator of BMP signaling, was found to be overexpressed at the mRNA and protein levels in liver of genetically hypotransferrinemic mice (Trf(hpx/hpx)). Soluble BMPER peptide inhibited BMP2- and BMP6-dependent hepcidin promoter activity in both HepG2 and HuH7 cells. These effects correlated with reduced cellular levels of pSMAD1/5/8. Addition of BMPER peptide to primary human hepatocytes abolished the BMP2-dependent increase in hepcidin mRNA, whereas injection of Bmper peptide into mice resulted in reduced liver hepcidin and increased serum iron levels. Thus Bmper may play an important role in suppressing hepcidin production in hypotransferrinemic mice.

The nutritional deficiencies provoked by ethanol consumption, during gestation or lactation, can contribute to multiple birth defects in offspring. In order to improve our knowledge about selenium (Se) distribution in pups exposed to ethanol, the present study evaluated the effect of this drug on intestinal development and determined its action on duodenal absorption of selenomethionine (Se-Met). To determinate if supplementation could improve Se absorption and its serum values, we used two antioxidant supplemented regimens on dams, with selenium alone or selenium plus folic acid, and obtained six groups of pups: C (control), A (alcohol), CS (control + Se), AS (alcohol + Se), CFS (control + Se + folic acid) and AFS (alcohol + Se + folic acid). Duodenal Se-Met transport was performed using an in vivo perfusion method. Se levels were measured by graphite furnace atomic absorption spectrometry. The supplemented diets utilized had a positive influence on body growth, duodenal perimeter and Se content in ethanol-exposed pups. Ethanol exposure increased Se-Met duodenal absorption in all pups, supplemented or not, presenting the highest values of maximal velocity (V(max)) compared with their control counterparts. The affinity constant (K(m)) increased according to rank: A>AS>AFS groups. These results suggest that although antioxidant supplementation does not restore Se-Met absorption to normal values, it enhances the affinity of the transporters for the substrate and improves the damage caused by ethanol in the duodenal mucosa.

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 (5 mg/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.

Despite Fe deficiency having been widely studied, the sequence of events in its development still remains unclear. The aim of the present study was to elucidate the effects of nutritional Fe-deficiency development on haematological parameters, Fe bioavailability and the enzymes involved in oxidative defence in recently weaned male Wistar albino rats. Control (C) and Fe-deficient (ID) groups were fed the AIN-93 G diet with a normal Fe level (45 mg/kg diet) or with a low Fe level (5 mg/kg diet), respectively, for 20, 30 or 40 d. At day 20 serum Fe, serum ferritin and the saturation of transferrin decreased drastically, decreasing further in the course of Fe-deficiency development for the saturation of transferrin. The development of Fe deficiency did not affect plasma thiobarbituric acid-reactive substance production, or catalase (CAT) and glutathione peroxidase (GPx) activities in erythrocyte cytosol. Fe deficiency diminished hepatic Fe content and CAT and GPx activities in hepatic cytosol only at day the 20. However, in spite of the minor Fe deposits in the brain of ID rats, the CAT and GPx activities in the brain cytosolic fraction did not differ in any of the studied periodsv.control rats. These results show that brain is a tissue that does not seem to depend on Fe levels for the maintenance of antioxidant defence mechanisms in the course of nutritional Fe deficiency.

Little information is available on the relationship of Se deposit in target organs and GPx activity in iron deficiency anemia. As red blood cells (RBCs) play a crucial role on Se metabolism and during Fe deficiency anemia a lower count of RBCs is featured, we aimed to investigate the influence of this pathology on Se bioavailability and the relationship with antioxidant status. 20 male Wistar rats were randomly divided into two groups, a control group receiving AIN-93G diet with normal Fe content (45mg/kg diet) and the Fe-deficient group receiving AIN-93G diet with low Fe content (5mg/kg diet) for 40 days. Both diets were prepared with an adequate Se content (0.180mg/kg diet). The digestive and metabolic utilization of Se, the distribution in target organ, the GPx activity and TBARS production were measured after receiving the diets. Se retention increased (P0.001) in the anemic group, fact that contributes to keep the enzymatic antioxidant activity of GPx in normal levels and the tendency observed is that stored Se increased in the organs, especially in kidney (P0.01), however, a lower Se deposit was found in sternum of anemic rats (P0.001). The lower count of RBCs featured in this pathology (P0.001) causes a decrease of Se concentration in sternum meanwhile the increase in kidney deposit is a consequence of the lower urinary losses (P0.001).

Objective The aim of this study was to examine the synergism of dietary calcium enrichment (added to goat's or cow's milk) and induced nutritional ferropenic anemia on oxidative status. Methods Control rats and rats with induced nutritional ferropenic anemia were fed for 14 d with diets containing normal (5000 mg/kg) or double (10 000 mg/kg) the recommended calcium content. Thiobarbituric acid-reactive substances in plasma were measured, as were the activities of the antioxidant enzyme catalase, copper/zinc superoxide dismutase, and glutathione peroxidase in erythrocyte cytosol. Results Dietary calcium enrichment did not affect oxidative stress as assessed by thiobarbituric acid-reactive substances; however, it significantly upregulated the activities of some antioxidant enzymes examined in the erythrocyte cytosol. In particular, adding calcium to standard or milk-based diets significantly increased glutathione peroxidase activity in control and anemic rats and copper/zinc superoxide dismutase activity in control rats. Conclusion The increased activities of glutathione peroxidase and copper/zinc superoxide dismutase induced by dietary calcium enrichment suggest that calcium supplementation may protect against oxidative stress even in nutritionally induced ferropenic anemia.

Objective: Oxidative stress results from an imbalance between the formation and neutralization of pro-oxidants. Disturbance of the pro-oxidant/antioxidant balance is also considered to be a causative factor underlying oxidative damage to cellular molecules, such as DNA, causing strand breaks. There is considerable controversy about the antioxidant status in iron-deficiency anemia (IDA), but scant information is available regarding DNA integrity. In the present study, we investigated the relation between DNA stability and hepatic antioxidant capacity in rats with induced IDA. Methods: Peripheral DNA damage was assessed using an alkaline comet assay. Further, the hepatic antioxidant enzyme glutathione peroxidase and the production of thiobarbituric acid-reactive substances were measured in control rats and in those with induced IDA. Results: Comparison of the control and anemic rats showed no differences in thiobarbituric acid-reactive substances production in the cytosolic fraction of hepatic cells. Nor were there any differences in liver glutathione peroxidase enzyme activity or DNA stability, as demonstrated by the percentage of DNA in the head (90.77 in control rats versus 88.23 in anemic rats), tail (9.23 in control rats versus 11.76 in anemic rats), and olive tail moment (0.155 in control rats versus 0.141 in anemic rats). Conclusion: IDA does not affect DNA stability or lipid peroxidation in rats, suggesting that there is enough compensatory capacity to keep antioxidant defenses high.