RESUMO
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.
Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Antioxidantes/metabolismo , Etanol/toxicidade , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Selênio/metabolismo , Animais , Aleitamento Materno , Etanol/administração & dosagem , Feminino , Transtornos do Espectro Alcoólico Fetal/prevenção & controle , Glutationa Peroxidase/metabolismo , Lactação , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Placenta/metabolismo , Gravidez , Ratos , Ratos Wistar , Glutationa Peroxidase GPX1RESUMO
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.
Assuntos
Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Consumo Excessivo de Bebidas Alcoólicas/tratamento farmacológico , Suplementos Nutricionais , Hepatopatias Alcoólicas/prevenção & controle , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Selenito de Sódio/farmacologia , Fatores Etários , Alanina Transaminase/sangue , Animais , Anti-Inflamatórios/farmacologia , Aspartato Aminotransferases/sangue , Consumo Excessivo de Bebidas Alcoólicas/sangue , Consumo Excessivo de Bebidas Alcoólicas/imunologia , Consumo Excessivo de Bebidas Alcoólicas/patologia , Caspase 3/metabolismo , Citocinas/sangue , Citoproteção , Modelos Animais de Doenças , Glutationa Peroxidase/metabolismo , Humanos , Mediadores da Inflamação/sangue , Fígado/imunologia , Fígado/metabolismo , Fígado/patologia , Hepatopatias Alcoólicas/sangue , Hepatopatias Alcoólicas/imunologia , Hepatopatias Alcoólicas/patologia , Masculino , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Ratos Wistar , Selenoproteínas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo , Consumo de Álcool por Menores , Glutationa Peroxidase GPX1RESUMO
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.
Assuntos
Desenvolvimento Fetal/efeitos dos fármacos , Síndrome Metabólica/sangue , Selênio/sangue , Fatores Sexuais , Animais , Animais Recém-Nascidos , Biomarcadores/sangue , Glicemia/metabolismo , Índice de Massa Corporal , Peso Corporal , Colesterol/sangue , Feminino , Frutose/administração & dosagem , Frutose/sangue , Polipeptídeo Inibidor Gástrico/sangue , Glucagon/sangue , Glutationa Peroxidase/sangue , Homeostase/efeitos dos fármacos , Insulina/sangue , Leptina/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Síndrome Metabólica/diagnóstico , Osteopontina/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ligante RANK/metabolismo , Ratos , Ratos Wistar , Triglicerídeos/sangue , Tri-Iodotironina/sangueRESUMO
Despite Fe deficiency and overload having been widely studied, no studies are available about the influence of milk consumption on antioxidant defence and lipid peroxidation during the course of these highly prevalent cases. The objective of the present study was to assess the influence of cow or goat milk-based diets, either with normal or Fe-overload, on antioxidant defence and lipid peroxidation in the liver, brain and erythrocytes of control and anaemic rats after chronic Fe repletion. Weanling male rats were randomly divided into two groups: a control group receiving a normal-Fe diet (45 mg/kg) and an anaemic group receiving a low-Fe diet (5 mg/kg) for 40 d. Control and anaemic rats were fed goat or cow milk-based diets, either with normal Fe or Fe-overload (450 mg/kg), for 30 or 50 d. Fe-deficiency anaemia did not have any effect on antioxidant enzymes or lipid peroxidation in the organs studied. During chronic Fe repletion, superoxide dismutase (SOD) activity was higher in the group of animals fed the cow milk diet compared with the group consuming goat milk. The slight modification of catalase and glutathione peroxidise activities in animals fed the cow milk-based diet reveals that these enzymes are unable to neutralise and scavenge the high generation of free radicals produced. The animals fed the cow milk diet showed higher rates of lipid peroxidation compared with those receiving the goat milk diet, which directly correlated with the increase in SOD activity. It was concluded that goat milk has positive effects on antioxidant defence, even in a situation of Fe overload, limiting lipid peroxidation.
Assuntos
Antioxidantes/metabolismo , Bovinos , Cabras , Sobrecarga de Ferro/metabolismo , Peroxidação de Lipídeos/fisiologia , Leite/química , Fenômenos Fisiológicos da Nutrição Animal , Animais , Dieta , Esquema de Medicação , Ferro/administração & dosagem , Ferro/efeitos adversos , Masculino , Distribuição Aleatória , Ratos , Especificidade da Espécie , Superóxido Dismutase , Substâncias Reativas com Ácido TiobarbitúricoRESUMO
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.