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.

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.

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 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.

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.

Ethanol consumption by Wistar rat dams affects selenium bioavailability and antioxidant balance in their progeny.

Ethanol consumption affects maternal nutrition, the mothers' antioxidant balance and the future health of their progeny. Selenium (Se) is a trace element cofactor of the enzyme glutathione peroxidase (GPx). We will study the effect of ethanol on Se bioavailability in dams and in their progeny. We have used three experimental groups of dams: control, chronic ethanol and pair-fed; and three groups of pups. Se levels were measured by graphite-furnace atomic absorption spectrometry. Serum and hepatic GPx activity was determined by spectrometry. We have concluded that ethanol decreased Se retention in dams, affecting their tissue Se deposits and those of their offspring, while also compromising their progeny's weight and oxidation balance. These effects of ethanol are caused by a reduction in Se intake and a direct alcohol-generated oxidation action.