Selenite supplementation modulates the hepatic metabolic sensors AMPK and SIRT1 in binge drinking exposed adolescent rats by avoiding oxidative stress.

Binge drinking (BD) is the main alcohol consumption pattern among teenagers. Recently, oxidative stress (OS) generated by BD exposure has been related to hepatic metabolic deregulation and cardiovascular dysfunction. This study analyzed if BD by generating oxidative stress modulates the alteration in hepatic energy homeostasis through two important regulators of energy metabolism: the NAD+-dependent sirtuin deacetylase (SIRT1) and AMP-activated protein kinase (AMPK) and if supplementation with the antioxidant selenium (Se) improves these metabolic disorders. Four groups of adolescent rats supplemented or not with Se (0.4 ppm) and exposed to intermittent i.p. BD were used. BD rats showed an increased AST/ALT ratio, total bilirubin in serum and lipid peroxidation in the liver. The BD rats also showed a higher abdominal/thoracic ratio and increased levels of TG, gluc, and chol compared to the control group, provoking an increase in mean blood pressure (MBP). This alcohol consumption pattern decreased hepatic Se deposits, cytoplasmic GPx activity, and GSH levels as well as the expressions of two metabolic sensors and the pAMPK/AMPK ratio. Se supplementation restored antioxidant parameters and decreased lipid oxidation, avoiding OS and improving the hepatic expression of pAMPK and SIRT1, contributing to the improvement of metabolic (better lipid profile and IRS-1 expression) and vascular function (lower MBP), and to the increase of hepatic functionality (lower AST/ALT ratio). All these actions decrease cardiometabolic risk factor development in the short and long term and could disrupt the relationship between BD and MS, two problems which are currently affecting adolescents.

Different effects on zinc redistribution if ethanol is consumed before or immediately after birth.

AIMS: The effect of ethanol consumption, either during pregnancy and/or lactation, on the altered metabolism of zinc (Zn) is not well-defined. Therefore, this study was performed to analyse the effect of chronic ethanol exposure on Zn redistribution in dams and offspring during either gestation and/or lactation. METHODS: We have used three groups of Wistar rat dams: control (CD), ethanol (ED), and pair-fed dams (PD). Some of the newborns were cross-fostered to dams at birth and we formed five experimental groups of offspring: control (CO); those exposed to ethanol during gestation only (GO); those exposed to ethanol during lactation only (LO); those exposed to ethanol during both periods (EO); and pair-fed groups (PO). Zn levels were measured by flame atomic absorption spectrophotometry. RESULTS: Zinc distribution is altered in ED with respect to CD, presenting significantly higher Zn values in the brain and spleen, and lower levels in the liver. However, total organs Zn levels are similar between dams. Ethanol-treated offspring (GO, LO, EO) consumed significantly less Zn than the CO. However, LO and EO showed significantly higher Zn serum levels. Zn distribution was altered in ethanol-treated offspring. GO and LO showed lower Zn levels in liver than CO; GO presents the lowest Zn liver levels. These levels were significantly lower than EO and PO. Ethanol-treated pups present significantly higher spleen and testes values than CO and PO. Total organ Zn levels were significantly lower in GO. CONCLUSIONS: Maternal adaptation resulted in organ Zn retention in order to meet the demands of pup's growth in the face of a lower diet intake. However, there was a redistribution of Zn in organ contents. Therefore, the ethanol route administration (via placenta and/or milk) affects Zn redistribution in pups in a different way.

Alcohol, gestation and breastfeeding: selenium as an antioxidant therapy.

AIM: The aim of this paper is to study the relationship between alcohol, selenium and oxidative stress in breastfeeding rat pups exposed to ethanol during gestation and lactation. We have also studied how a Se-supplemented diet among mothers could prevent different oxidative liver disorders in the pups. METHOD: Pups of 21 days were randomized into four groups: control group (C), alcohol group (A), alcohol selenium group (AS) and control selenium group (CS). Alcohol was supplied to their mothers for 13 weeks (induction, reproduction, gestation and lactation periods). The selenium-supplemented diet contained 0.5 ppm as selenite. We determined serum and liver selenium by graphite-furnace atomic absorption spectrometry. We measured antioxidant enzyme activities: glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT) and superoxide dismutase (SOD); and lipid peroxidation (TBARS) and protein carbonyl (PC) by a spectrophotometric method in the liver. RESULTS: In the liver of pups, exposure to ethanol provoked a decrease in selenium and GPx activity and an increase in GR and CAT activity, as well as in carbonyl groups in protein. A pups had higher Se levels and GPx activity in serum than C pups. Administering Se with alcohol balances the activities of scavenging enzymes and reduces peroxidation protein products. CONCLUSION: These results suggest that selenium could be effective in neutralizing the damage of ethanol consumption during gestation and lactation in pups since it repairs selenium levels in liver as well as the activity of scavenging enzymes and peroxidation protein products. In serum, Se also recovers GPx activity and increases the levels of Se that are available to other organs.

Lipid metabolism in ethanol-treated rat pups and adults: effects of folic Acid.

AIMS: In this study we determined whether a folic acid-supplemented diet could change hyperlipaemia provoked by chronic ethanol intake in adult and pup rats. METHODS: Animals were randomized into eight groups (four adults and four pups): control groups, water and basic diet; alcohol groups, 20% ethanol and basic diet; alcohol folic acid groups, 20% ethanol and diet supplemented with folic acid; control folic acid groups, water and folic acid-supplemented diet. We determined serum and liver total cholesterol (Chol), HDL, triglycerides (TG), phospholipids (PL) and bile acids (BA) levels in all of the groups. Hydroxymethylglutaryl-CoA (HMG-CoA) reductase activity was also measured in the livers. RESULTS: Ethanol-fed rats have higher serum HDL and PL levels in pups and higher serum LDL, TG and PL levels in adults than controls and supplemented animals with or without alcohol ingestion. Ethanol provokes an increase in hepatic Chol and BA, and a decrease in hepatic TG and PL in pups; in adults it also provokes an increase in hepatic Chol and BA and a significant increase in HMG-CoA reductase activity. Alcohol intake plus folic acid supplementation has no effects on these values except BA levels that were significantly higher, in both pups and adult rats, than in the control group. CONCLUSION: Despite the fact that alcohol intake provokes different lipid alterations in adults and in pups whose mothers drank ethanol, folic acid contributes to the alleviation of these adverse effects reducing HMG-CoA reductase activity in adult rats and, except BA levels, to normalizing lipids values due to the fact that folic acid acts as a choleretic compound. We can therefore assume that folic acid supplementation reduces alcohol-induced hypercholesterolaemia by decreasing synthesis and increasing catabolism.