Maternal ethanol consumption reduces Se antioxidant function in placenta and liver of embryos and breastfeeding pups.

AIM: The fetal alcohol exposition during pregnancy leads to different disorders in offspring, related to the oxidative stress generated by alcohol. It is well-documented that there is an impairment of the antioxidant selenoprotein Glutathione peroxidase (GPx) activity in ethanol offspring during the embryo period, although no-one has described Selenium (Se) status. The aim is to analyze for the first time Se deposits in vivo and Se's biological implication in embryos and placenta after alcohol exposure and in offspring whose mothers continued to drink ethanol during lactation. MATERIALS AND METHODS: Se deposits, GPx and glutathione reductase (GR) activity, lipid and protein oxidation and the expression of GPx1 were measured in placenta and liver of both embryos (E-19) and breastfeeding pups (L-21) in control and ethanol groups (20% v/v). KEY FINDINGS: Ethanol consumption decreased Se deposits, GPx activity and GPx1 expression, while increasing biomolecular oxidation in placenta and in the liver of E-19 and L-21. The GR/GPx ratio decreased in placenta and in E-19, together with an increase in lipid oxidation, while increased in the liver of L-21 pups with protein oxidation. Ethanol also decreased the GPx1 expression/GPx activity ratio in the liver of E-19 and L-21, indicating that alcohol decreases GPx activity by both depleting Se deposits and promoting GPx inactivation. In placenta GPx activity is proportional to the GPx1 expression found, so the ethanol affects GPx activity in offspring more than in dams. SIGNIFICANCE: Therefore, Se supplementation therapy in dams could contribute as an interesting antioxidant that prevents fetal alcohol syndrome.

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.

Metabolic syndrome and selenium during gestation and lactation.

PURPOSE: Selenium (Se) has a dual role in metabolic syndrome (MS) development as it has an antioxidant action against both "good" and "bad" reactive oxygen species. This study evaluates Se body profile in dams which present MS during gestation and lactation, in order to elucidate a normal dietary Se's implication in this pathology. METHOD: Rats were randomized into control (C) and fructose (F) groups. The rich fructose diet (65 %) during gestation and lactation periods induced MS in dams. Se body distribution was determined by atomic absorption spectrophotometry, and the hepatic activity of the four antioxidant enzymes and the bimolecular oxidation were determined by spectrophotometry. The cardiac activity was monitored using the indirect tail occlusion method. Lipid and glucidic profile was also analyzed. RESULTS: Despite the fact that the diet supplied has 0.1 ppm of Se, the minimal dietary requirement for rats, F dams ate less amount of food, and therefore, they had lower Se retention. However, they had normal levels of Se in serum and milk. Dams with MS had Se depletion in heart and muscle joint to hypertension and a lower heart rate, and Se repletion in liver and kidney. Despite the increase in hepatic glutathione peroxidase (GPx) and catalase activity found, lipid oxidation occurred-probably because superoxide dismutase activity was diminished. In heart, the activity and expression of the selenoprotein GPx1 were decreased. CONCLUSION: With these results, it is not possible to elucidate whether a dietary Se supplementation or a Se-restricted diet are good for MS; because despite the fact that GPx activity is increased in liver, it is also found, for the first time, that heart Se deposits are significantly decreased during MS.

Metabolic syndrome and selenium in fetal programming: gender differences.

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.

Serum selenium levels and oxidative balance as differential markers in hepatic damage caused by alcohol.

AIMS: Antioxidant system abnormalities have been associated with ethanol consumption. This study examines the effects of chronic ethanol consumption on oxidative balance, including selenium (Se) levels in alcoholic patients with or without liver disease, and if these measurements could be indicative of liver disease. MAIN METHODS: Serum Se levels, antioxidant enzymes' activities, malondialdehyde (MDA) and protein carbonyl (PC) were determined in three groups of patients: alcoholics without liver disease, alcoholics with liver disease, and non-alcoholics with liver disease; and in healthy volunteers. KEY FINDINGS: Serum Se levels were lower in alcoholic patients and in patients affected by liver disease and especially lower in the alcoholic liver disease group. These values were correlated with the activity of glutathione peroxidase (GPx), the antioxidant selenoprotein. The antioxidant activities of the glutathione reductase (GR) and superoxide dismutase (SOD) were also lower in the three non-healthy groups. However, GR activity decreased and SOD activity increased in the non-alcoholic liver disease group versus alcoholic groups. Higher concentrations of PC in serum were found in non-healthy groups and were higher in alcoholic patients who also showed higher MDA levels. The highest MDA and PC levels were found in the alcoholic liver disease group. SIGNIFICANCE: We conclude that serum Se levels are drastically decreased in alcoholic liver disease patients, showing that this element has a direct correlation with GPx activity, and lipid oxidation, suggesting that the serum Se/MDA ratio could be an indicator of hepatic damage caused by alcohol consumption, and pointing to Se as a possible antioxidant therapy.

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 dietary supplementation as a mechanism to restore hepatic selenoprotein regulation in rat pups exposed to alcohol.

Ethanol exposure during gestation and lactation decreases selenium (Se) intake, disrupting body Se balance and inducing oxidative stress in rat offspring. Selenium-supplemented diet (0.5 ppm) was administered to ethanol-exposed (20% v/v) dams during gestation and lactation. When the dams' pups were 21 days old, the pups' levels of the main hepatic selenoproteins glutathione peroxidase (GPx1 and GPx4) and selenoprotein P (SelP) were measured. The pups were divided into control (C), alcohol (A), control-selenium (CS), and alcohol-selenium (AS) groups. The purpose was to evaluate the effect of the selenium-supplemented diet on the levels of Se deposits present in the livers of their pups. Alcohol decreases hepatic Se deposits, GPx activity, and GPx1 expression; alcohol increases GPx4 and SelP expression. Se was measured by furnace graphite atomic absorption spectrometry, the antioxidant activity of GPx and concentration of hepatic phospholipids (PL) were determined by spectrophotometry, and the selenoprotein expressions were detected by Western blotting. Selenite treatment prevented alcohol's effects of diminishing the Se deposits, GPx activity, and GPx1 expression, while maintaining the high levels of the expression of GPx4 and SelP. These results suggest that depletion of hepatic Se levels in rat pups, caused by ethanol exposure to their dams, affects the synthesis of the 3 main hepatic selenoproteins in different ways, which is related to a decrease in GPx activity and PL concentration, and an increase in serum Se levels. Selenium supplementation to the dams increased the expression of GPx1, GPx4, and SelP in their pups.

Effects of antioxidant supplementation on duodenal Se-Met absorption in ethanol-exposed rat offspring in vivo.

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.