Folic acid antioxidant supplementation to binge drinking adolescent rats improves hydric-saline balance and blood pressure, but fails to increase renal NO availability and glomerular filtration rate.

Binge drinking (BD) is an especially pro-oxidant pattern of alcohol consumption, particularly widespread in the adolescent population. In the kidneys, it affects the glomerular filtration rate (GFR), leading to high blood pressure. BD exposure also disrupts folic acid (FA) homeostasis and its antioxidant properties. The aim of this study is to test a FA supplementation as an effective therapy against the oxidative, nitrosative, and apoptotic damage as well as the renal function alteration occurred after BD in adolescence. Four groups of adolescent rats were used: control, BD (exposed to intraperitoneal alcohol), control FA-supplemented group and BD FA-supplemented group. Dietary FA content in control groups was 2 ppm, and 8 ppm in supplemented groups. BD provoked an oxidative imbalance in the kidneys by dysregulating antioxidant enzymes and increasing the enzyme NADPH oxidase 4 (NOX4), which led to an increase in caspase-9. BD also altered the renal nitrosative status affecting the expression of the three nitric oxide (NO) synthase (NOS) isoforms, leading to a decrease in NO levels. Functionally, BD produced a hydric-electrolytic imbalance, a low GFR and an increase in blood pressure. FA supplementation to BD adolescent rats improved the oxidative, nitrosative, and apoptotic balance, recovering the hydric-electrolytic equilibrium and blood pressure. However, neither NO levels nor GFR were recovered, showing in this study for the first time that NO availability in the kidneys plays a crucial role in GFR regulation that the antioxidant effects of FA cannot repair.

Augmentation of a Transosseous-Equivalent Repair in Posterosuperior Nonacute Rotator Cuff Tears With a Bioinductive Collagen Implant Decreases the Retear Rate at 1 Year: A Randomized Controlled Trial.

PURPOSE: To determine whether the addition of a bioinductive collagen implant (BCI) over a transosseous equivalent (TOE) repair of medium-to-large posterosuperior rotator cuff tears improves the healing rate determined by magnetic resonance imaging (MRI) at 12-month follow-up. METHODS: A Level I randomized controlled trial was performed in 124 subjects with isolated, symptomatic, reparable, full-thickness, medium-to-large posterosuperior nonacute rotator cuff tears, with fatty infiltration ≤2. These were randomized to 2 groups in which an arthroscopic posterosuperior rotator cuff tear TOE repair was performed alone (Control group) or with BCI applied over the TOE repair (BCI group). The primary outcome was the retear rate (defined as Sugaya 4-5) determined by MRI at 12 months of follow-up. Secondary outcomes were characteristics of the tendon (Sugaya grade and thickness of the healed tendon) and clinical outcomes (pain levels, EQ-5D-5L, American Shoulder and Elbow Surgeons, and Constant-Murley scores) at 12 months of follow-up. RESULTS: Of the 124 randomized patients, 122 (60 in the BCI group and 62 in the Control group) were available for MRI evaluation 12.2 ± 1.02 months after the intervention. There were no relevant differences in preoperative characteristics. Adding the BCI reduced the retear rate (8.3% [5/60] in the BCI group vs 25.8% [16/62] in the Control group, P = .010; relative risk of retear of 0.32 [95% confidence interval 0.13-0.83]). Sugaya grade was also better in the BCI group (P = .030). There were no differences between groups in the percentage of subjects who reached the MCID for CMS (76.7% vs 81.7%, P = .654) or American Shoulder and Elbow Surgeons (75% vs 80%, P = .829), in other clinical outcomes or in complication rates at 12.4 ± 0.73 (range 11.5-17) months of follow-up. CONCLUSIONS: Augmentation with a BCI of a TOE repair in a medium-to-large posterosuperior rotator cuff tear reduces the retear rate at 12-month follow-up by two-thirds, yielding similar improvements in clinical outcomes and without increased complication rates. LEVEL OF EVIDENCE: Level I, randomized controlled trial.

High- and low- selenium diets affect endocrine energy balance during early programming.

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.

Maternal selenium status is profoundly involved in metabolic fetal programming by modulating insulin resistance, oxidative balance and energy homeostasis.

PURPOSE: High and low levels of selenium (Se) have been related to metabolic disorders in dams and in their offspring. Their relationship to oxidative balance and to AMP-activated protein kinase (AMPK) is some of the mechanisms proposed. The aim of this study is to acquire information about how Se is involved in metabolic programming. METHODS: 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, the pups' metabolic profile, oxidative balance, Se levels, selenoproteins and IRS-1 hepatic expression, as well as hepatic AMPK activation were measured. RESULTS: The experimental groups present deep changes in Se homeostasis, selenoproteins and IRS-1 hepatic expression, oxidative balance, AMPK activation ratio and insulin levels. They do, however, have different metabolic profiles. CONCLUSIONS: High- and low-Se diets are linked to insulin resistance, yet the mechanisms involved are completely opposite.

Binge drinking during adolescence disrupts Se homeostasis and its main hepatic selenoprotein expression.

BACKGROUND: Binge drinking (BD) is the most common ethanol (EtOH) intake consumption model among teenagers, but little is known about its effects on the liver. During its hepatic metabolism, acute alcohol exposure produces a great amount of reactive oxygen species which contributes to alcohol-induced liver injury. Selenium (Se) plays a key role in antioxidant defense as it forms part of selenoproteins, such as the antioxidant glutathione peroxidases (GPxs) or the selenoprotein P (SelP), synthesized mainly in liver. Chronic EtOH consumption decreases both Se deposits and this tissue's antioxidant activity. METHODS: Two BD administration routes (oral and intraperitoneal) were used in adolescent rats to analyze Se homeostasis; the main hepatic selenoproteins' expression: GPx1, GPx4, and SelP, and their biological roles related to oxidation. Their relationship with inflammatory processes was also determined by analyzing the expression of the transcriptional factor nuclear factor-kappa beta (NF-κB). RESULTS: It has been demonstrated for the first time that BD in adolescents alters Se homeostasis regardless of the administration route employed, despite the fact that the BD oral group ingested less Se in diet. This decrease of Se in serum and liver is directly related to a decrease in serum GPx3 and hepatic GPx1 activity, contributing to the oxidative imbalance found. The depletion of Se detected in liver affects GPx1 expression and, surprisingly, GPx4 expression. This could be related to the lower expression of the transcriptional factor NF-κB in the liver, a key player in the regulation of inflammatory processes. CONCLUSIONS: Due to the above, and to find whether a Se supplementation therapy improves these situations, it would be interesting to explore in more depth the relationship between Se, the high oxidation found, and the depressed immune response reported in BD adolescents.

Oral or intraperitoneal binge drinking and oxidative balance in adolescent rats.

Oxidative imbalance is one of the most important mechanisms of alcohol-induced injury. Acute alcohol exposure induces a significant amount of reactive oxygen species during its hepatic metabolism via the microsomal ethanol oxidizing system. During adolescence, the physiological development is still taking place; therefore, ethanol's effects differ in adolescents compared to that in adults. Because binge drinking is the most important model of ethanol intake used by adolescents and because little is known about its effects on the liver, we have used two routes of acute ethanol administration (oral and intraperitoneal) in adolescent rats in order to analyze the oxidative damage caused in the periphery and liver. Here, it has been demonstrated for the first time that binge drinking in adolescents causes peripheral oxidation of lipid and DNA as well as lipid and protein hepatic oxidation, which are related to lower glutathione peroxidise (GPx) activity, higher catalase (CAT) activity, and higher expression of NADPHoxidase, contributing to hepatic damage. In addition, it is shown that the intraperitoneal administration route results in increased oxidative damage, which is probably related to the resulting general stress response that causes higher DNA and protein oxidation due to higher NADPHoxidase expression and higher CAT and superoxide dismutase (SOD) activities. According to these results, it is concluded that binge drinking induces hepatic damage during adolescence, at least in part, as consequence of oxidative stress because the antioxidant response was insufficient to avoid liver oxidation. Alcohol administered intraperitoneally provoked more DNA oxidation than that from the oral alcohol exposure model.

Selenium supplementation via modulation of selenoproteins ameliorates binge drinking-induced oxidative, energetic, metabolic, and endocrine imbalance in adolescent rats' skeletal muscle.

Adolescence is characterized by increased vulnerability to addiction and ethanol (EtOH) toxicity, particularly through binge drinking (BD), a favored acute EtOH-ingestion pattern among teenagers. BD, highly pro-oxidant, induces oxidative stress (OS), affecting skeletal muscle (SKM), where selenium (Se), an antioxidant element and catalytic center of selenoproteins, is stored, among other tissues. Investigating the effects of Se supplementation on SKM after BD exposure holds therapeutic promise. For this, we randomised 32 adolescent Wistar rats into 4 groups, exposed or not to intermittent i.p. BD [BD and control (C)] (3 g EtOH per kg per day), and supplemented with selenite [BDSe and CSe] (0.4 ppm). In SKM, we examined the oxidative balance, energy status (AMPK, SIRT-1), protein turnover (IRS-1, Akt1, mTOR, IGF-1, NF-κB p65, MAFbx, ULK1, pelF2α), serum myokines (myostatin, IL-6, FGF21, irisin, BDNF, IL-15, fractalkine, FSTL-1, FABP-3), and selenoproteins (GPx1, GPx4, SelM, SelP). In the pancreas, we studied the oxidative balance and SIRT-1 expression. Selenite supplementation mitigated BD-induced OS by enhancing the expression of selenoproteins, which restored oxidative balance, notably stimulating protein synthesis and normalizing the myokine profile, leading to improved SKM mass growth and metabolism, and reduced inflammation and apoptosis (caspase-3). Selenite restoration of SelP's receptor LRP1 expression, reduced by BD, outlines the crucial role of SKM in the SelP cycle, linking Se levels to SKM development. Furthermore, Se attenuated pancreatic OS, preserving insulin secretion. Se supplementation shows potential for alleviating SKM damage from BD, with additional beneficial endocrine effects on the pancreas, adipose tissue, liver, heart and brain that position it as a broad-spectrum treatment for adolescent alcohol consumption, preventing metabolic diseases in adulthood.

Uncovering the Role of Selenite and Selenium Nanoparticles (SeNPs) in Adolescent Rat Adipose Tissue beyond Oxidative Balance: Transcriptomic Analysis.

Studies on adolescent rats, when body composition is changing deeply, reveal that the administration of sodium selenite and selenium nanoparticles (SeNPs), at the same dose, have opposite effects on adipogenesis in white adipose tissue (WAT). To investigate the mechanisms involved in these contrasting effects by means of transcriptomic analysis, three groups of male adolescent rats (n = 18) were used: control (C), selenite supplemented (S), and SeNPs supplemented (NS). Both treated groups received a twofold increase in Se dose compared to the control group through water intake for three weeks. Following treatment, WAT was removed and frozen at -80 °C until subsequent use for RNA extraction, endogenous antioxidant enzymatic activities determination, and quantification of H2O2 and malondialdehyde. NS rats displayed a larger number of differentially expressed genes and cellular processes impacted than S rats. Remarkably, these changes involved upregulation of gene expression associated with the immune system, catabolism, mitochondrial function, and oxidative balance. NS rats presented an increase in antioxidant enzymes activity, alongside an accumulation of H2O2 and malondialdehyde levels. The expression level of 81 genes related to oxidative stress was significantly affected in NS rats. Analyzing the KEGG pathway enrichment revealed that NS rats exhibited increased activity in key catabolic pathways and decreased activity in crucial growth signaling processes. These changes contribute to the mass decrease in WAT found in NS rats. These results suggest a possible application of SeNPs in WAT reduction and induction of the immune response during adolescence.

Selenium, selenoproteins and cancer of the thyroid.

Selenium is an essential mineral element with important biological functions for the whole body through incorporation into selenoproteins. This element is highly concentrated in the thyroid gland. Selenoproteins provide antioxidant protection for this tissue against the oxidative stress caused by free radicals and contribute, via iodothyronine deiodinases, to the metabolism of thyroid hormones. It is known that oxidative stress plays a major role in carcinogenesis and that in recent decades there has been an increase in the incidence of thyroid cancer. The anti-carcinogenic action of selenium, although not fully understood, is mainly attributable to selenoproteins antioxidant properties, and to the ability to modulate cell proliferation (cell cycle and apoptosis), energy metabolism, and cellular immune response, significantly altered during tumorigenesis. Researchers have suggested that different forms of selenium supplementation may be beneficial in the prevention and treatment of thyroid cancer; however, the studies have several methodological limitations. This review is a summary of the current knowledge on how selenium and selenoproteins related to thyroid cancer.

Binge drinking leads to an oxidative and metabolic imbalance in skeletal muscle during adolescence in rats: endocrine repercussion.

Binge drinking (BD) is an especially pro-oxidant model of alcohol consumption, mainly used by adolescents. It has recently been related to the hepatic IR-process. Skeletal muscle is known to be involved in insulin action and modulation through myokine secretion. However, there is no information on muscle metabolism and myokine secretion after BD exposure in adolescents. Two experimental groups of adolescent rats have been used: control and BD-exposed one. Oxidative balance, energy status and lipid, and protein metabolism have been analyzed in muscle, together with myokine serum levels (IL-6, myostatin, LIF, IL-5, fractalkine, FGF21, irisin, BDNF, FSTL1, apelin, FABP3, osteocrin, osteonectin (SPARC), and oncostatin). In muscle, BD affects the antioxidant enzyme balance leading to lipid and protein oxidation. Besides, it also increases the activation of AMPK and thus contributes to decrease SREBP1 and pmTOR and to increase FOXO3a expressions, promoting lipid and protein degradation. These alterations deeply affect the myokine secretion pattern. This is the first study to examine a general myokine response after exposure to BD. BD not only caused a detrimental imbalance in myokines related to muscle turnover, decreased those contributing to increase IR-process, decreased FST-1 and apelin and their cardioprotective function but also reduced the neuroprotective BDNF. Consequently, BD leads to an important metabolic and energetic disequilibrium in skeletal muscle, which contributes to exacerbate a general IR-process.

Microbiota-Liver-Bile Salts Axis, a Novel Mechanism Involved in the Contrasting Effects of Sodium Selenite and Selenium-Nanoparticle Supplementation on Adipose Tissue Development in Adolescent Rats.

Adolescence is a period during which body composition changes deeply. Selenium (Se) is an excellent antioxidant trace element related to cell growth and endocrine function. In adolescent rats, low Se supplementation affects adipocyte development differently depending on its form of administration (selenite or Se nanoparticles (SeNPs). Despite this effect being related to oxidative, insulin-signaling and autophagy processes, the whole mechanism is not elucidated. The microbiota-liver-bile salts secretion axis is related to lipid homeostasis and adipose tissue development. Therefore, the colonic microbiota and total bile salts homeostasis were explored in four experimental groups of male adolescent rats: control, low-sodium selenite supplementation, low SeNP supplementation and moderate SeNPs supplementation. SeNPs were obtained by reducing Se tetrachloride in the presence of ascorbic acid. Supplementation was received orally through water intake; low-Se rats received twice more Se than control animals and moderate-Se rats tenfold more. Supplementation with low doses of Se clearly affected anaerobic colonic microbiota profile and bile salts homeostasis. However, these effects were different depending on the Se administration form. Selenite supplementation primarily affected liver by decreasing farnesoid X receptor hepatic function, leading to the accumulation of hepatic bile salts together to increase in the ratio Firmicutes/Bacteroidetes and glucagon-like peptide-1 (GLP-1) secretion. In contrast, low SeNP levels mainly affected microbiota, moving them towards a more prominent Gram-negative profile in which the relative abundance of Akkermansia and Muribaculaceae was clearly enhanced and the Firmicutes/Bacteroidetes ratio decreased. This bacterial profile is directly related to lower adipose tissue mass. Moreover, low SeNP administration did not modify bile salts pool in serum circulation. In addition, specific gut microbiota was regulated upon administration of low levels of Se in the forms of selenite or SeNPs, which are properly discussed. On its side, moderate-SeNPs administration led to great dysbiosis and enhanced the abundance of pathogenic bacteria, being considered toxic. These results strongly correlate with the deep change in adipose mass previously found in these animals, indicating that the microbiota-liver-bile salts axis is also mechanistically involved in these changes.

Selenium or selenium plus folic acid-supplemented diets ameliorate renal oxidation in ethanol-exposed pups.

BACKGROUND: Ethanol (EtOH) exposure during gestation and lactation induces an oxidative stress in offspring. In kidney, the oxidative damage is the primary pathway to alcohol-induced injury. In this study, we have demonstrated that a diet supplemented with selenium (Se) (0.5 ppm) or with Se (0.5 ppm) + folic acid (8 ppm) administered to EtOH-exposed (20% v/v) dams during gestation and lactation prevents the oxidative EtOH-provoked effects in their offspring's kidneys. METHODS: All the studies were performed on 21-day-old pups. Serum, urine, and kidney Se levels were assessed by graphite-furnace atomic absorption spectrometry. Se and creatinine clearance, antioxidant enzyme activities, and lipid and protein peroxidation were determined by a spectrophotometric method in kidney. RESULTS: Dietary supplementation treatments used could not improve the glomerular filtration function altered by EtOH exposure during gestation and lactation; however, they did improve renal Se deposits, renal development, and renal protein content while decreasing lipid and protein oxidation and modifying antioxidant enzymes' activity. CONCLUSIONS: Se or Se + folic acid supplementations improve renal development and protein content and modify antioxidant enzymes' activity, decreasing lipid and protein oxidation after EtOH exposure. In this context, a double-supplemented diet appears to reduce protein peroxidation more efficiently than the Se-only-supplemented one, probably via superoxide dismutase and catalase.

Dietary Selenium and Its Antioxidant Properties Related to Growth, Lipid and Energy Metabolism.

Selenium (Se) is an essential trace element mainly known for its antioxidant, anti-inflammatory and anti-apoptotic properties [...].

The Role of Selenoprotein Tissue Homeostasis in MetS Programming: Energy Balance and Cardiometabolic Implications.

Selenium (Se) is an essential trace element mainly known for its antioxidant, anti-inflammatory, and anti-apoptotic properties, as it is part of the catalytic center of 25 different selenoproteins. Some of them are related to insulin resistance (IR) and metabolic syndrome (MetS) generation, modulating reactive oxygen species (ROS), and the energetic sensor AMP-activated protein kinase (AMPK); they can also regulate the nuclear transcription factor kappa-B (NF-kB), leading to changes in inflammation production. Selenoproteins are also necessary for the correct synthesis of insulin and thyroid hormones. They are also involved in endocrine central regulation of appetite and energy homeostasis, affecting growth and development. MetS, a complex metabolic disorder, can appear during gestation and lactation in mothers, leading to energetic and metabolic changes in their offspring that, according to the metabolic programming theory, will produce cardiovascular and metabolic diseases later in life. However, there is a gap concerning Se tissue levels and selenoproteins' implications in MetS generation, which is even greater during MetS programming. This narrative review also provides an overview of the existing evidence, based on experimental research from our laboratory, which strengthens the fact that maternal MetS leads to changes in Se tissue deposits and antioxidant selenoproteins' expression in their offspring. These changes contribute to alterations in tissues' oxidative damage, inflammation, energy balance, and tissue function, mainly in the heart. Se imbalance also could modulate appetite and endocrine energy balance, affecting pups' growth and development. MetS pups present a profile similar to that of diabetes type 1, which also appeared when dams were exposed to low-Se dietary supply. Maternal Se supplementation should be taken into account if, during gestation and/or lactation periods, there are suspicions of endocrine energy imbalance in the offspring, such as MetS. It could be an interesting therapy to induce heart reprogramming. However, more studies are necessary.

Binge drinking during the adolescence period causes oxidative damage-induced cardiometabolic disorders: A possible ameliorative approach with selenium supplementation.

Binge drinking (BD) is the most common alcohol consumption model among adolescents. BD exposure during adolescence disrupts the nervous system function, being involved in the major mortality causes at this age: motor vehicle accidents, homicides and suicides. Recent studies have also shown that BD consumption during adolescence affects liver, renal and cardiovascular physiology, predisposing adolescents to future adult cardiometabolic damage. BD is a particularly pro-oxidant alcohol consumption pattern, because it leads to the production of a great source of reactive oxygen species (ROS) via the microsomal ethanol oxidizing system, also decreasing the antioxidant activity of glutathione peroxidase (GPx). Selenium (Se) is a mineral which plays a pivotal role against oxidation; it forms part of the catalytic center of different antioxidant selenoproteins such as GPxs (GPx1, GPx4, GPx3) and selenoprotein P (SelP). Specifically, GPx4 has an essential role in mitochondria, preventing their oxidation, apoptosis and NFkB-inflamative response, being this function even more relevant in heart's tissue. Se serum levels are decreased in acute and chronic alcoholic adult patients, being correlated to the severity of oxidation, liver damage and metabolic profile. Experimental studies have described that Se supplementation to alcohol exposed mice clearly decreases oxidative and liver damage. However, clinical BD effects on Se homeostasis and selenoproteins' tissue distribution related to oxidation during adolescence are not yet studied. In this narrative review we will describe the use of sodium selenite supplementation as an antioxidant therapy in adolescent BD rats in order to analyze Se homeostasis implication during BD exposure, oxidative balance, apoptosis and inflammation, mainly in liver, kidney, and heart. These biomolecular changes and the cardiovascular function will be analyzed. Se supplementation therapies could be a good strategy to prevent the oxidation, inflammation and apoptosis generated in tissues by BD during adolescence, such as liver, kidney and heart, improving cardiovascular functioning.

Inflammation and oxidative stress, the links between obesity and COVID-19: a narrative review.

COVID-19, an acute respiratory disease caused by SARS-CoV-2, has rapidly become a pandemic. On the other hand, obesity is also reaching dramatic dimensions and it is a risk factor for morbidity and premature mortality. Obesity has been linked to a high risk of serious-associated complications to COVID-19, due to the increased risk of concomitant chronic diseases, which highlights the health public relevance of the topic. Obese subjects have a pro-inflammatory environment, which can further exacerbate COVID-19-induced inflammation and oxidative stress, explaining the increased risk of serious complications in these patients. Another factor that favors infection in obese patients is the high expression of ACE2 receptors in the adipose tissue. The negative impact of COVID-19 in obesity is also associated with a decrease in respiratory function, the concurrence of multiple comorbidities, a low-degree chronic inflammatory state, immunocompromised situation, and therefore a higher rate of hospitalization, mechanical ventilation, in-hospital complications such as pneumonia, and death. In this review, the link between obesity and COVID-19 was analyzed, exploring the potential common mechanisms in both diseases, with special attention to oxidative stress and inflammation, due to the crucial role of both pathways in the development of the disease.

Folic Acid Homeostasis and Its Pathways Related to Hepatic Oxidation in Adolescent Rats Exposed to Binge Drinking.

Chronic ethanol consumption and liver disease are intimately related to folic acid (FA) homeostasis. Despite the fact that FA decreases lipid oxidation, its mechanisms are not yet well elucidated. Lately, adolescents have been practising binge drinking (BD), consisting of the intake of a high amount of alcohol in a short time; this is a particularly pro-oxidant form of consumption. The aim of this study is to examine, for the first time, FA homeostasis in BD adolescent rats and its antioxidant properties in the liver. We used adolescent rats, including control rats and rats exposed to an intermittent intraperitoneal BD model, supplemented with or without FA. Renal FA reabsorption and renal FA deposits were increased in BD rats; hepatic deposits were decreased, and heart and serum levels remained unaffected. This depletion in the liver was accompanied by higher transaminase levels; an imbalance in the antioxidant endogenous enzymatic system; lipid and protein oxidation; a decrease in glutathione (GSH) levels; hyper-homocysteinemia (HHcy); an increase in NADPH oxidase (NOX) 1 and NOX4 enzymes; an increase in caspase 9 and 3; and a decrease in the anti-apoptotic metallopeptidase inhibitor 1. Furthermore, BD exposure increased the expression of uncoupled endothelial nitric oxide synthase (eNOS) by increasing reactive nitrogen species generation and the nitration of tyrosine proteins. When FA was administered, hepatic FA levels returned to normal levels; transaminase and lipid and protein oxidation also decreased. Its antioxidant activity was due, in part, to the modulation of superoxide dismutase activity, GSH synthesis and NOX1, NOX4 and caspase expression. FA reduced HHcy and increased the expression of coupled eNOS by increasing tetrahydrobiopterin expression, avoiding nitrosative stress. In conclusion, FA homeostasis and its antioxidant properties are affected in BD adolescent rats, making it clear that this vitamin plays an important role in the oxidative, nitrosative and apoptotic hepatic damage generated by acute ethanol exposure. For this, FA supplementation becomes a potential BD therapy for adolescents, preventing future acute alcohol-related harms.

Different Effects of Low Selenite and Selenium-Nanoparticle Supplementation on Adipose Tissue Function and Insulin Secretion in Adolescent Male Rats.

Adolescence is a period of intense growth and endocrine changes, and obesity and insulin-resistance processes during this period have lately been rising. Selenium (Se) homeostasis is related to lipid metabolism depending on the form and dose of Se. This study tests the actions of low-dose selenite and Se nanoparticles (SeNPs) on white (WAT) and brown adipose tissue (BAT) deposition, insulin secretion, and GPx1, IRS-1 and FOXO3a expression in the WAT of adolescent rats as regards oxidative stress, adipocyte length and adipokine secretion. Four groups of male adolescent rats were treated: control (C), low selenite supplementation (S), low SeNP supplementation (NS) and moderate SeNP supplementation (NSS). Supplementation was received orally through water intake; NS and NSS rats received two- and tenfold more Se than C animals, respectively. SeNPs were obtained by reducing Se tetrachloride in the presence of ascorbic acid. For the first time in vivo, it was demonstrated that low selenite supplementation contributed to increased adipogenesis via the insulin signaling pathway and LCN2 modulation, while low SeNP administration prevented fat depots in WAT via the decrease in insulin signaling and FOXO3a autophagy in WAT, lowering inflammation. These effects were independent of GPx1 expression or activity in WAT. These findings provide data for dietary approaches to prevent obesity and/or anorexia during adolescence. These findings may be relevant to future studies looking at a nutritional approach aimed at pre-venting obesity and/or anorexia in adolescence.

Fetal Programming Is Deeply Related to Maternal Selenium Status and Oxidative Balance; Experimental Offspring Health Repercussions.

Nutrients consumed by mothers during pregnancy and lactation can exert permanent effects upon infant developing tissues, which could represent an important risk factor for diseases during adulthood. One of the important nutrients that contributes to regulating the cell cycle and tissue development and functionality is the trace element selenium (Se). Maternal Se requirements increase during gestation and lactation. Se performs its biological action by forming part of 25 selenoproteins, most of which have antioxidant properties, such as glutathione peroxidases (GPxs) and selenoprotein P (SELENOP). These are also related to endocrine regulation, appetite, growth and energy homeostasis. In experimental studies, it has been found that low dietary maternal Se supply leads to an important oxidative disruption in dams and in their progeny. This oxidative stress deeply affects gestational parameters, and leads to intrauterine growth retardation and abnormal development of tissues, which is related to endocrine metabolic imbalance. Childhood pathologies related to oxidative stress during pregnancy and/or lactation, leading to metabolic programing disorders like fetal alcohol spectrum disorders (FASD), have been associated with a low maternal Se status and intrauterine growth retardation. In this context, Se supplementation therapy to alcoholic dams avoids growth retardation, hepatic oxidation and improves gestational and breastfeeding parameters in FASD pups. This review is focused on the important role that Se plays during intrauterine and breastfeeding development, in order to highlight it as a marker and/or a nutritional strategy to avoid diverse fetal programming disorders related to oxidative stress.

Selenoproteins and renal programming in metabolic syndrome-exposed rat offspring.

Maternal metabolic syndrome (MS) during gestation and lactation leads to several cardiometabolic changes related to selenium (Se) status and selenoprotein expression in offspring. However, little is known about kidney programming and antioxidant selenoprotein status in MS pups. To gain more knowledge on this subject, two experimental groups of dam rats were used: Control (Se: 0.1 ppm) and MS (fructose 65% and Se: 0.1 ppm). At the end of lactation, Se deposits in kidneys, selenoprotein expression (GPx1, GPx3, GPx4 and selenoprotein P), oxidative balance and AMP-activated protein kinase (AMPK) and activated transcriptional factor NF-κB expression were measured. Kidney functional parameters, albuminuria, creatinine clearance, aldosteronemia, and water and electrolyte balance, were also evaluated. One week later systolic blood pressure was measured. Lipid peroxidation takes place in the kidneys of MS pups and Se, selenoproteins and NF-κB expression increased, while AMPK activation decreased. MS pups have albuminuria and low creatinine clearance which implies glomerular renal impairment with protein loss. They also present hypernatremia and hyperaldosteronemia, together with a high renal Na+ reabsorption, leading to a hypertensive status, which was detected in these animals one week later. Since these alterations seem to be related, at least in part, to oxidative stress, the increase in Se and selenoproteins found in the kidneys of these pups seems to be beneficial, avoiding a higher lipid oxidation. However, in order to analyze the possible global beneficial role of Se in kidneys during MS exposure, more data are necessary to document the relationships between GPx4 and NF-κB, and SelP and AMPK in kidneys.