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.

Adipose tissue homeostasis orchestrates the oxidative, energetic, metabolic and endocrine disruption induced by binge drinking in adolescent rats.

Binge drinking (BD) is the most common alcohol consumption model for adolescents, and has recently been related to the generation of high oxidation and insulin resistance (IR). White adipose tissue (WAT) is a target organ for insulin action that regulates whole-body metabolism by secreting adipokines. The present study aimed to analyse the oxidative, inflammatory, energetic and endocrine profile in the WAT of BD-exposed adolescent rats, to obtain an integrative view of insulin secretion and WAT in IR progression. Two groups of male adolescent rats were used: control (n = 8) and BD (n = 8). An intermittent i.p. BD model (20% v/v) was used during 3 consecutive weeks. BD exposure led to a pancreatic oxidative imbalance, which was joint to high insulin secretion by augmenting deacetylase sirtuin-1 (SIRT-1) pancreatic expression and serum adipsin levels. However, BD rats had hyperglycaemia and high homeostasis model assessment of insulin resistance value (HOMA-IR). BD exposure in WAT increased lipid oxidation, as well as decreased insulin receptor substrate 1 (IRS-1) and AKT expression, sterol regulatory element-binding protein 1 (SREBP1), forkhead box O3A (FOXO3a) and peroxisome proliferator-activated receptor γ (PPARγ), and adipocyte size. BD also affected the expression of proteins related to energy balance, such as SIRT-1 and AMP activated protein kinase (AMPK), affecting the adipokine secretion profile (increasing resistin/adiponectin ratio). BD altered the entire serum lipid profile, increasing the concentration of free fatty acids. In conclusion, BD led to an oxidative imbalance and IR process in WAT, which modified the energy balance in this tissue, decreasing the WAT lipogenic/lipolytic ratio, affecting adipokine secretion and the systemic lipid profile, and contributing to the progression of IR. Therefore, WAT is key in the generation of metabolic and endocrine disruption after BD exposure during adolescence in rats. KEY POINTS: Adolescent rat binge drinking (BD) exposure leads to hepatic and systemic oxidative stress (OS) via reactive oxygen species generation, causing hepatic insulin resistance (IR) and altered energy metabolism. In the present study, BD exposure in adolescent rats induces OS in the pancreas, with increased insulin secretion despite hyperglycaemia, indicating a role for IR in white adipose tissue (WAT) homeostasis. In WAT, BD produces IR and an oxidative and energetic imbalance, triggering an intense lipolysis where the serum lipid profile is altered and free fatty acids are increased, consistent with liver lipid accumulation and steatosis. BD exposure heightens inflammation in WAT, elevating pro-inflammatory and reducing anti-inflammatory adipokines, favouring cardiovascular damage. This research provides a comprehensive view of how adolescent BD in rats impacts liver, WAT and pancreas homeostasis, posing a risk for future cardiometabolic complications in adulthood.

Selenium, a dietary-antioxidant with cardioprotective effects, prevents the impairments in heart rate and systolic blood pressure in adolescent rats exposed to binge drinking treatment.

BACKGROUND: Binge drinking (BD) during adolescence is related to cardiovascular alterations. Selenium (Se) is an essential trace element with antioxidant, anti-inflammatory and antiapoptotic properties, essential for correct heart function. OBJECTIVES: To study the protective cardiovascular effects of selenium in adolescent rats exposed to a BD-like procedure. METHODS: 32 adolescent male rats exposed to an intraperitoneally BD-like model or not, and supplemented with 0.4ppm of selenite or not, were divided into 4 groups: control, alcohol, control-selenium and alcohol-selenium. Blood pressure and heart rate (HR) were determined after experimentation. Se deposits, oxidative balance and the expression of glutathione peroxidases (GPxs), NF-kB and caspase-3 were measured in the heart. Also, DNA instability in rat lymphocytes and serum vascular markers were determined. Statistical analysis was performed with the ANOVA model. RESULTS: The BD-like model depleted Se heart deposits (p < .01), decreased GPx activity (p < .01) and GPx1 (p < .001) and GPx4 (p < .05) expression, increased NF-kB (p < .01), caspase-3 (p < .001) expression, and generated oxidation in myocytes. Outside the heart, the BD-like model caused double-strand breaks in lymphocyte DNA and increased all the vascular markers measured. These cardiovascular alterations were related to higher systolic (p < .001) and diastolic (p < .05) blood pressure and HR (p < .05). In the heart, Se supplementation in BD-exposed rats significantly increased Se deposits (p < .001) and improved oxidative balance and vascular damage, including increased GPxs and decreased NF-kB and caspase-3 activation, consequently decreasing systolic (p < .05) blood pressure and HR (p < .01). CONCLUSIONS: Se supplementation presents cardioprotective effects since it reversed HR and systolic blood pressure observed in BD-exposed adolescent rats.

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.

The role of folic acid and selenium against oxidative damage from ethanol in early life programming: a review.

There are disorders in children, covered by the umbrella term "fetal alcohol spectrum disorder" (FASD), that occur as result of alcohol consumption during pregnancy and lactation. They appear, at least in part, to be related to the oxidative stress generated by ethanol. Ethanol metabolism generates reactive oxygen species and depletes the antioxidant molecule glutathione (GSH), leading to oxidative stress and lipid and protein damage, which are related to growth retardation and neurotoxicity, thereby increasing the incidence of FASD. Furthermore, prenatal and postnatal exposure to ethanol in dams, as well as increasing oxidation in offspring, causes malnutrition of several micronutrients such as the antioxidant folic acid and selenium (Se), affecting their metabolism and bodily distribution. Although abstinence from alcohol is the only way to prevent FASD, it is possible to reduce its harmful effects with a maternal dietary antioxidant therapy. In this review, folic acid and Se have been chosen to be analyzed as antioxidant intervention systems related to FASD because, like ethanol, they act on the methionine metabolic cycle, being related to the endogenous antioxidants GSH and glutathione peroxidase. Moreover, several birth defects are related to poor folate and Se status.

Biological implications of selenium in adolescent rats exposed to binge drinking: Oxidative, immunologic and apoptotic balance.

Alcohol intermittent binge drinking (BD) during adolescence decreases the levels of selenium (Se), a trace element that plays a key biological role against oxidative damage in hepatocytes through different selenoproteins such as the antioxidant enzymes glutathione peroxidases (GPx1 and Gpx4) and selenoprotein P (SelP). In this context, it has been found that GPx4 has an essential antioxidant role in mitochondria modulating the apoptosis and NF-kB activation (a factor intimately related to apoptosis and immune function). To further investigate the effectiveness of selenium supplementation in oxidative balance, inflammation and apoptosis, the present study examined the protective effects of 0.4ppm of dietary selenite administrated to adolescent rats exposed to BD. BD consumption depleted Se deposits in all the tissues studied. In liver, GPx1 activity and expression were decreased leading to protein and lipid hepatic oxidation. Moreover GPx4 and NF-kB expression were also decreased in liver, coinciding with an increase in caspase-3 expression. This hepatic profile caused general liver damage as shown the increased serum transaminases ratio AST/ALT. Proinflammatory serum citokines and chemocines were decreased. Se supplementation therapy used restored all these values, even AST levels. These findings suggest for first time that Se supplementation is a good strategy against BD liver damage during adolescence, since it increases GPx1 and GPx4 expression and avoids NF-kB downregulation and caspase-3 upregulation, leading to a better oxidative, inflammatory and apoptotic liver profile. The therapy proposed could be considered to have a great biological efficacy and to be suitable for BD exposed teenagers in order to avoid future hepatic complications.

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.

Role of selenium and glutathione peroxidase on development, growth, and oxidative balance in rat offspring.

Selenium (Se), an essential trace metal, is important in both growth and reproduction and is the constituent of different selenoproteins. The glutathione peroxidase (GPx) family is the most studied as it prevents oxidative stress. Liver oxidation is considered as another mechanism involved in low birth weight. Therefore, in order to ascertain whether GPx is related to the effects of Se on growth during gestation and lactation, three groups of rat pups were used: control, Se deficient (SD), and Se supplemented (SS). Morphological parameters and reproductive indices were evaluated. Hepatic Se levels were measured by graphite furnace atomic absorption while spectrophotometry was used for activity of antioxidant enzymes and oxidative stress markers in liver and western blotting for expression of hepatic GPx1 and GPx4. The SD diet increased mortality at birth; decreased viability and survival indices; and stunted growth, length, and liver development in offspring, thus decreasing hepatic Se levels, GPx, glutathione reductase, and catalase activities, while increasing superoxide dismutase activity and protein oxidation. The SS diet counteracted all the above results. GPx1 expression was heavily regulated by Se dietary intake; however, although Se dietary deficiency reduced GPx4 expression, this decrease was not as pronounced. Therefore, it can be concluded that Se dietary intake is intimately related to growth, length, and directly regulating GPx activity primarily via GPx1 and secondly to GPx4, thus affecting liver oxidation and development. These results suggest that if risk of uterine growth retardation is suspected, or if a neonate with low birth weight presents with signs of liver oxidation, it may be beneficial to know about Se status.

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.

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.