RESUMEN
Down syndrome (DS) is the most common chromosomal disorder, resulting from the failure of normal chromosome 21 segregation. Studies have suggested that impairments within the one-carbon metabolic pathway can be of relevance for the global genome instability observed in mothers of individuals with DS. Based on the association between global DNA hypomethylation, genome instability, and impairments within the one-carbon metabolic pathway, the present study aimed to identify possible predictors, within the one-carbon metabolism, of global DNA methylation, measured by methylation patterns of LINE-1 and Alu repetitive sequences, in mothers of individuals with DS and mothers of individuals without the syndrome. In addition, we investigated one-carbon genetic polymorphisms and metabolites as maternal predisposing factors for the occurrence of trisomy 21 in children. Eighty-three samples of mothers of children with DS with karyotypically confirmed free trisomy 21 (case group) and 84 of mothers who had at least one child without DS or any other aneuploidy were included in the study. Pyrosequencing assays were performed to access global methylation. The results showed that group affiliation (case or control), betaine-homocysteine methyltransferase (BHMT) G742A and transcobalamin 2 (TCN2) C776G polymorphisms, and folate concentration were identified as predictors of global Alu DNA methylation values. In addition, thymidylate synthase (TYMS) 28-bp repeats 2R/3R or 3R/3R genotypes are independent maternal predisposing factors for having a child with DS. This study adds evidence that supports the association of impairments in the one-carbon metabolism, global DNA methylation, and the possibility of having a child with DS.
Asunto(s)
Carbono/metabolismo , Metilación de ADN/genética , Síndrome de Down/genética , Síndrome de Down/metabolismo , Estudio de Asociación del Genoma Completo , Inestabilidad Genómica/genética , Relaciones Madre-Hijo , Madres , Adolescente , Adulto , Anciano , Elementos Alu/genética , Betaína-Homocisteína S-Metiltransferasa/genética , Betaína-Homocisteína S-Metiltransferasa/metabolismo , Femenino , Ácido Fólico/metabolismo , Predisposición Genética a la Enfermedad/genética , Humanos , Elementos de Nucleótido Esparcido Largo/genética , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Transducción de Señal/genética , Transducción de Señal/fisiología , Timidilato Sintasa/genética , Transcobalaminas/genética , Transcobalaminas/metabolismo , Adulto JovenRESUMEN
INTRODUCTION: Background: folic acid participates in one-carbon metabolism, which supplies methyl groups to numerous reactions in the body. Impaired delivery of these methyl groups affects gene expression. We hypothesize that offspring exposed to less folic acid will express higher levels of Pomc (proopiomelanocortin) gene mRNA. Aim: to investigate the Pomc gene and protein expression pattern in the female offspring of female rats receiving a folic acid-deficient diet during gestation, lactation, and post-weaning. Methods: the study involved female rat offspring (n = 10) born from mothers subjected to a control (2.0 mg of folic acid/kg of food) or folic acid-deficient (0.5 mg of folic acid/kg of food) diet, and fed the same diet during post-weaning. Samples were collected from the arcuate nucleus of the hypothalamus of the female offspring for real-time PCR and Western blotting analyses. Results: the female offspring in the folic acid-deficient diet group had significantly higher Pomc gene and protein expression than the female offspring in the control diet group (p = 0.03, p = 0.01, respectively). Conclusion: a folic acid-deficient diet during gestation, lactation, and post-weaning increases Pomc gene and protein expression, but does not modify food intake or body weight of female rat offspring.
INTRODUCCIÓN: Antecedentes: el ácido fólico participa en el metabolismo de un solo carbono, que suministra grupos metilo a numerosas reacciones del cuerpo. La aportación alterada de estos grupos metilo afecta a la expresión génica. Nuestra hipótesis es que la descendencia expuesta a menos ácido fólico expresará niveles más altos de ARNm del gen Pomc (proopiomelanocortina). Objetivo: investigar el patrón de expresión del gen Pomc y de sus proteínas en crías de ratas hembras que recibieron una dieta deficiente en ácido fólico durante la gestación, la lactancia y el destete. Métodos: el estudio incluyó crías hembras (n = 10) nacidas de madres sometidas a una dieta control (2,0 mg de ácido fólico/kg de alimento) o deficiente en ácido fólico (0,5 mg de ácido fólico/kg de alimento) durante la gestación y la lactancia, y alimentadas con la misma dieta durante el destete. Se recolectaron muestras del núcleo arqueado del hipotálamo de las hembras para el análisis de la expresión génica (PCR en tiempo real) y de proteínas (inmunomanchado Western). Resultados: las hembras pertenecientes al grupo de dieta deficiente en ácido fólico tuvieron una expresión del gen Pomc y sus proteínas significativamente mayor que la de las hembras pertenecientes al grupo con dieta de control (p = 0,03, p = 0,01, respectivamente). Conclusión: la dieta deficiente en ácido fólico durante la gestación, la lactancia y el destete modifica la expresión del gen Pomc y sus proteínas pero no modifica la ingesta de alimentos ni el peso corporal de las ratas hembra.
Asunto(s)
Dieta , Ácido Fólico/administración & dosificación , Proopiomelanocortina/biosíntesis , Proopiomelanocortina/genética , Destete , Animales , Animales Recién Nacidos , Femenino , Expresión Génica , Embarazo , Ratas , Ratas WistarRESUMEN
SCOPE: Nutrition is a major contributing factor for immunocompetence. The aim was to assess the immune status of older people after consuming milk produced by lactating cows fed with one of the following diets: control diet (C), C + vitamin E + selenium (C + A), C + sunflower oil (C + O), and C + sunflower oil + vitamin E + selenium (A + O). METHODS AND RESULTS: Sixty elderly people received one of these biofortified milks for 12 weeks. Immune response was assessed by measurement of the expression of COX-1, COX-2, MCP-1, PPAR (δ, α, and ß/δ) genes, neutrophil production of oxygen reactive species induced by immune complexes, neutrophil phagocytosis and lytic activity of the alternative pathway of the complement system, and cytokine levels. Variables were assessed before and after treatment. Our findings showed stability of some inflammatory mediators (complement activity and neutrophils burst) in treatment groups, except complement activity in C + A, and an increase of these markers in C, especially reactive oxygen species production and phagocytic activity. TNF-α was significantly increased in all groups. In C + A, IL-4 and IL-2 increased after treatment, and in the group that received the milk produced by cows fed with "O" diet, CCL20 and IL-27 increased. CONCLUSION: Overall, as compared to C, milk biofortification was associated with stabilization of the activity of alternative complement pathway and the neutrophils burst, and modulated different cytokines levels.
Asunto(s)
Vía Alternativa del Complemento , Ácidos Grasos/administración & dosificación , Alimentos Fortificados , Leche , Neutrófilos/inmunología , Selenio/administración & dosificación , Vitamina E/administración & dosificación , Anciano , Anciano de 80 o más Años , Animales , Bovinos , Citocinas/análisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Especies Reactivas de Oxígeno/metabolismoRESUMEN
BACKGROUND: Nonalcoholic steatohepatitis is considered the hepatic manifestation of metabolic syndrome and it is particularly associated to the insulin resistance, hypertension, obesity and abnormalities in lipid and glucose metabolism. OBJECTIVE: Considering the importance of obesity and oxidative stress in the pathophysiology of nonalcoholic steatohepatitis, this study aimed to evaluate the presence and association of the obesity and oxidative stress in this pathology. METHODS: Fifteen outpatients with nonalcoholic steatohepatitis (nonalcoholic steatohepatitis group), diagnosed according to the histopathological findings from the liver biopsy, and 15 body mass index-matched subjects (non nonalcoholic steatohepatitis group) without nonalcoholic steatohepatitis were included. All volunteers were registered in a Brazilian University Hospital. Nutritional assessment (weight, height, body mass index and waist circumference) and biochemical analysis (fasting glucose, liver enzymes, lipid profile, leptin, superoxide dismutase, glutathione peroxidase, vitamins C and E, catalase and 8-isoprostane) were performed for all the participants. The student t test was used for statistical analysis, with P<0.05 as the significant factor. RESULTS: Nonalcoholic steatohepatitis patients had higher fasting glucose, hepatic enzymes (serum aspartate aminotransaminase, alanine aminotransaminase, gamma glutamyl transferase, alkaline phosphatase), triglycerides and superoxide dismutase and lower glutathione peroxidase values than non nonalcoholic steatohepatitis individuals. CONCLUSION: This paper demonstrates that only the presence of obesity is not enough to trigger alterations in all the studied biomarkers. Despite the majority of oxidative stress markers being found to be similar in both conditions, the nonalcoholic steatohepatitis subjects could be slightly more affected than the non nonalcoholic steatohepatitis individuals.
Asunto(s)
Enfermedad del Hígado Graso no Alcohólico/etiología , Obesidad/complicaciones , Estrés Oxidativo/fisiología , Adolescente , Adulto , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Obesidad/fisiopatología , Factores de Riesgo , Adulto JovenRESUMEN
BackgroundNonalcoholic steatohepatitis is considered the hepatic manifestation of metabolic syndrome and it is particularly associated to the insulin resistance, hypertension, obesity and abnormalities in lipid and glucose metabolism.ObjectiveConsidering the importance of obesity and oxidative stress in the pathophysiology of nonalcoholic steatohepatitis, this study aimed to evaluate the presence and association of the obesity and oxidative stress in this pathology.MethodsFifteen outpatients with nonalcoholic steatohepatitis (nonalcoholic steatohepatitis group), diagnosed according to the histopathological findings from the liver biopsy, and 15 body mass index-matched subjects (non nonalcoholic steatohepatitis group) without nonalcoholic steatohepatitis were included. All volunteers were registered in a Brazilian University Hospital. Nutritional assessment (weight, height, body mass index and waist circumference) and biochemical analysis (fasting glucose, liver enzymes, lipid profile, leptin, superoxide dismutase, glutathione peroxidase, vitamins C and E, catalase and 8-isoprostane) were performed for all the participants. The student t test was used for statistical analysis, with P<0.05 as the significant factor.ResultsNonalcoholic steatohepatitis patients had higher fasting glucose, hepatic enzymes (serum aspartate aminotransaminase, alanine aminotransaminase, gamma glutamyl transferase, alkaline phosphatase), triglycerides and superoxide dismutase and lower glutathione peroxidase values than non nonalcoholic steatohepatitis individuals.ConclusionThis paper demonstrates that only the presence of obesity is not enough to trigger alterations in all the studied biomarkers. Despite the majority of oxidative stress markers being found to be similar in both conditions, the nonalcoholic steatohepatitis subjects could be slightly more affected than the non nonalcoholic steatohepatitis individuals.
ContextoEsteatohepatite não alcoólica é considerada uma manifestação hepática da síndrome metabólica e está particularmente associada com a resistência insulínica, hipertensão, obesidade, anormalidades no metabolismo lipídico e da glicose.ObjetivoConsiderando a importância da obesidade e do estresse oxidativo na fisiopatogenia da esteatohepatite não alcoólica, o objetivo deste estudo foi avaliar a associação e presença da obesidade e do estresse oxidativo nesta patologia.MétodosQuinze pacientes com esteatohepatite não alcoólica (grupo esteatohepatite não alcoólica), diagnosticados de acordo com os achados histopatológicos da biópsia hepática, e 15 indivíduos sem esteatohepatite não alcoólica com sobrepeso/obesidade (grupo sem esteatohepatite não alcoólica) foram incluídos. Todos os voluntários eram acompanhados em Hospital Universitário Brasileiro. Avaliação nutricional (peso, altura, índice de massa corporal e circunferência abdominal) e bioquímica (glicemia de jejum, enzimas hepáticas, lipidograma, leptina, superóxido dismutase, glutationa peroxidase, vitaminas C e E, catalase e 8-isoprostano) foram realizadas em todos os indivíduos. O teste t de Student foi usado para análise estatística considerando o P≤0,05 como significativo.ResultadosIndivíduos do Grupo esteatohepatite não alcoólica apresentaram valores significativamente maiores de glicemia, AST, ALT, Gama GT, fosfatase alcalina, triglicérides e superóxido dismutase e menor valor de glutationa peroxidase, quando comparados ao Grupo sem esteatohepatite não alcoólica.ConclusãoEste artigo demonstra que somente a presença da obesidade não é suficiente para provocar alterações nos biomarcadores estudados. Apesar da maioria dos marcadores de estresse oxidativo apresentarem-se similar nas duas condições, os pacientes com esteatohepatite não alcoólica podem apresentar-se levemente mais afetados que os indivíduos sem esteatohepatite não alcoólica.
Asunto(s)
Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Enfermedad del Hígado Graso no Alcohólico/etiología , Obesidad/complicaciones , Estrés Oxidativo/fisiología , Biomarcadores/sangre , Estudios de Casos y Controles , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Obesidad/fisiopatología , Factores de RiesgoRESUMEN
Idosos institucionalizados apresentam um risco aumentado de alteração do estado nutricional. Sendo assim, são necessários indicadores sensíveis para identificação da alteração do estado nutricional. O objetivo deste estudo é avaliar indicadores para análise do estado nutricional de idosos institucionalizados, em um período de três meses, por meio de exames bioquímicos e antropométricos. Foram selecionados 81 voluntários, com 78 ± 10 anos, sendo 53% do sexo feminino. Os dados antropométricos evidenciaram que as variáveisíndice de massa corporal, peso, massa gorda e ângulo de fase dos idosos institucionalizados diminuíram em três meses com diferença significativa no período. Dentre todos os exames bioquímicos e antropométricos, as variáveis índice de massa corporal, peso, massa gorda, ângulo de fase e lipidograma foram os indicadores da avaliação nutricional que identificaram alterações precoces e riscos nutricionais dos idosos institucionalizados no período de três meses. Vale ressaltar que indicadores nutricionais avaliados precocemente podem evitar os riscos nutricionais de idosos institucionalizados.
Institutionalized elderly have an increased risk of changes in nutritional status, therefore sensitive parameters are necessary for the identification of changes in nutritional status. The aim of this study was to evaluate parameters for analysis of the nutritional status of institutionalized elderly in a period of three months by means of biochemical and anthropometric measurements. Eighty one volunteers were selected, with 78 ± 10 years old and 53% female. Anthropometric data showed that the variables body mass index, weight, fat mass, and phase angle of the institutionalized elderly in three months decreased with significant difference between the assessments. Among all the biochemical and anthropometric measurements, body mass index, weight, fat mass, phase angle and blood fat were the indicators of nutritional assessment that identified early changes and nutritional risks of institutionalized elderly in three months. It is noteworthy that the early evaluation of nutritional indicators can prevent nutritional risk among elderly in living in rest homes.
Asunto(s)
Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fenómenos Fisiológicos Nutricionales del Anciano , Hogares para Ancianos/estadística & datos numéricos , Institucionalización/estadística & datos numéricos , Evaluación Nutricional , Casas de Salud/estadística & datos numéricos , Estado Nutricional/fisiología , Adiposidad/fisiología , Índice de Masa Corporal , Brasil , Peso Corporal/fisiología , Proteína C-Reactiva/análisis , Cuidados a Largo Plazo , Fuerza Muscular/fisiología , Estadísticas no ParamétricasRESUMEN
This study investigates the treatment of non-alcoholic fatty liver disease (NAFLD) in rats with choline and fructooligosaccharide (FOS). The healthy control group received standard diet. The other three groups consisted of animals with NAFLD. Group Estr received standard diet; group Echo received standard diet plus choline (3 g/100 g diet); and group Efos received standard diet plus FOS (10 g/100 g diet). Food intake, weight, urinary nitrogen, urinary ammonia, total cholesterol, serum triacylglyceride, liver and heart weights, tissue nitrogen, tissue fat, vitamin E, TBARS, and reduced glutathione (GSH) were measured in hepatic and heart tissue. Choline and FOS treatments resulted in total mean fat reduction in liver and heart tissue of 0.2 and 1.7 g, respectively. Both treatments were equally effective in reducing hepatic and cardiac steatosis. There were no differences in the TBARS level among experimental and control groups, indicating that the proposed treatments had no added protection against free radicals. While all experimental groups had increased vitamin E and GSH levels, choline treatment led to a significant increase compared to control.
RESUMEN
Flaky paint dermatosis, characterized by extensive, often bilateral areas of flaking and pigmentation, mostly in sun unexposed areas is considered a feature of kwashiorkor in both children and adults, and must be differentiated from other dermatosis, including chapped and xerotica skin, and pellagra. In this case series we provide evidence that malnourished patients with flaky paint dermatosis and infection/inflammation shown laboratory data suggestive of indoleamine 2,3-dioxygenase (IDO) activation, besides decreased urinary excretion of N1-methylnicotinamide (N1 MN), a marker of pellagra. We study nine adult patients showing flaky paint dermatosis and clinical features of infection or inflammation, and increased serum C-reactive protein, characteristic of the presence of acute phase response syndrome. As a group, they had low or deficient urinary N1 MN excretion (0.52 ± 0.39 mg/g creatinine) compatible with pellagra. They also showed low serum tryptophan levels (<29 µmol/L) and a serum kynurenine/tryptophan ratio higher than 0.04, suggesting increased IDO expression and increase in the tryptophan oxidation. Findings suggest that some patients with flaky paint dermatosis showed laboratory data suggestive of IDO activation, besides decreased N1 MN urinary excretion. Taken together, the data support the idea that flaky paint dermatosis could be a skin manifestation of niacin deficiency.
Asunto(s)
Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Kwashiorkor/complicaciones , Niacina/metabolismo , Pelagra/complicaciones , Enfermedades de la Piel/etiología , Piel/patología , Triptófano/sangre , Reacción de Fase Aguda/etiología , Reacción de Fase Aguda/metabolismo , Adulto , Anciano , Proteína C-Reactiva/metabolismo , Humanos , Indoles/metabolismo , Kwashiorkor/metabolismo , Kwashiorkor/patología , Quinurenina/sangre , Persona de Mediana Edad , Niacina/deficiencia , Niacinamida/análogos & derivados , Niacinamida/orina , Pelagra/metabolismo , Pelagra/patología , Enfermedades de la Piel/metabolismoRESUMEN
This study aimed to examine the benefits of different amounts of omega-3 (n-3) polyunsaturated fatty acids from fish oil (FO) on lipid metabolism, insulin resistance and gene expression in rats fed a high-fructose diet. Male Wistar rats were separated into two groups: Control (C, n = 6) and Fructose (Fr, n = 32), the latter receiving a diet containing 63% by weight fructose for 60 days. After this period, 24 animals from Fr group were allocated to three groups: FrFO2 (n = 8) receiving 63% fructose and 2% FO plus 5% soybean oil; FrFO5 (n = 8) receiving 63% fructose and 5% FO plus 2% soybean oil; and FrFO7 (n = 8) receiving 63% fructose and 7% FO. Animals were fed these diets for 30 days. Fructose led to an increase in liver weight, hepatic and serum triacylglycerol, serum alanine aminotransferase and HOMA1-IR index. These alterations were reversed by 5% and 7% FO. FO had a dose-dependent effect on expression of genes related to hepatic ß-oxidation (increased) and hepatic lipogenesis (decreased). The group receiving the highest FO amount had increased markers of oxidative stress. It is concluded that n-3 fatty acids may be able to reverse the adverse metabolic effects induced by a high fructose diet.
Asunto(s)
Modelos Animales de Enfermedad , Ácidos Docosahexaenoicos/uso terapéutico , Ácido Eicosapentaenoico/uso terapéutico , Resistencia a la Insulina , Hígado/metabolismo , Síndrome Metabólico/dietoterapia , Triglicéridos/metabolismo , Animales , Biomarcadores/sangre , Biomarcadores/metabolismo , Carbohidratos de la Dieta/efectos adversos , Suplementos Dietéticos/efectos adversos , Ácidos Docosahexaenoicos/administración & dosificación , Ácidos Docosahexaenoicos/efectos adversos , Ácido Eicosapentaenoico/administración & dosificación , Ácido Eicosapentaenoico/efectos adversos , Aceites de Pescado/administración & dosificación , Aceites de Pescado/efectos adversos , Aceites de Pescado/uso terapéutico , Fructosa/efectos adversos , Regulación Enzimológica de la Expresión Génica , Peroxidación de Lípido , Hígado/patología , Hígado/fisiopatología , Masculino , Síndrome Metabólico/metabolismo , Síndrome Metabólico/patología , Síndrome Metabólico/fisiopatología , Tamaño de los Órganos , Estrés Oxidativo , Distribución Aleatoria , Ratas Wistar , Triglicéridos/sangreRESUMEN
Fasting and then refeeding on a high-carbohydrate diet increases serum and hepatic triacylglycerol (TAG) concentrations compared to standard diets. Fructose is a lipogenic monosaccharide which stimulates de novo fatty acid synthesis. Omega-3 (n-3) fatty acids stimulate hepatic ß-oxidation, partitioning fatty acids away from TAG synthesis. This study investigated whether dietary n-3 fatty acids from fish oil (FO) improve the hepatic lipid metabolic response seen in rats fasted and then refed on a high-fructose diet. During the post-prandial (fed) period, rats fed a FO rich diet showed an increase in hepatic peroxisome proliferator-activated receptor α (PPAR-α) gene expression and decreased expression of carbohydrate responsive element binding protein (ChREBP), fatty acid synthase (FAS) and microsomal triglyceride transfer protein (MTTP). Feeding a FO rich diet for 7 days prior to 48 h of fasting resulted in lower hepatic TAG, lower PPAR-α expression and maintenance of hepatic n-3 fatty acid content. Refeeding on a high fructose diet promoted an increase in hepatic and serum TAG and in hepatic PPAR-α, ChREBP and MTTP expression. FO did not prevent the increase in serum and hepatic TAG after fructose refeeding, but did decrease hepatic expression of lipogenic genes and increased the n-3 fatty acid content of the liver. n-3 Fatty acids can modify some components of the hepatic lipid metabolic response to later feeding with a high fructose diet.
Asunto(s)
Dieta , Carbohidratos de la Dieta/efectos adversos , Ayuno/fisiología , Aceites de Pescado/farmacología , Fructosa/efectos adversos , Lipogénesis/efectos de los fármacos , Hígado/efectos de los fármacos , Animales , Peso Corporal , Proteínas Portadoras/metabolismo , Carbohidratos de la Dieta/administración & dosificación , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-3/uso terapéutico , Aceites de Pescado/uso terapéutico , Expresión Génica , Lipogénesis/genética , Hígado/metabolismo , Masculino , PPAR alfa/metabolismo , Periodo Posprandial , Ratas Wistar , Triglicéridos/metabolismoRESUMEN
Institutionalized elderly have an increased risk of changes in nutritional status, therefore sensitive parameters are necessary for the identification of changes in nutritional status. The aim of this study was to evaluate parameters for analysis of the nutritional status of institutionalized elderly in a period of three months by means of biochemical and anthropometric measurements. Eighty one volunteers were selected, with 78 ± 10 years old and 53% female. Anthropometric data showed that the variables body mass index, weight, fat mass, and phase angle of the institutionalized elderly in three months decreased with significant difference between the assessments. Among all the biochemical and anthropometric measurements, body mass index, weight, fat mass, phase angle and blood fat were the indicators of nutritional assessment that identified early changes and nutritional risks of institutionalized elderly in three months. It is noteworthy that the early evaluation of nutritional indicators can prevent nutritional risk among elderly in living in rest homes.
Asunto(s)
Fenómenos Fisiológicos Nutricionales del Anciano , Hogares para Ancianos/estadística & datos numéricos , Institucionalización/estadística & datos numéricos , Casas de Salud/estadística & datos numéricos , Evaluación Nutricional , Estado Nutricional/fisiología , Adiposidad/fisiología , Anciano , Índice de Masa Corporal , Peso Corporal/fisiología , Brasil , Proteína C-Reactiva/análisis , Femenino , Humanos , Cuidados a Largo Plazo , Masculino , Persona de Mediana Edad , Fuerza Muscular/fisiología , Estadísticas no ParamétricasRESUMEN
There is no consensus about the effects of conjugated linoleic acid (CLA) on lipid metabolism, especially in animals fed a high-fat diet. Therefore, the objective of the present study was to evaluate the incorporation of CLA isomers into serum, liver and adipose tissue, as well as the oxidative stress generated in rats refed with high-fat diets after a 48 hour fast. Rats were refed with diets containing soybean oil, rich in linoleic acid [7% (Control Group - C) or 20% (LA Group)], CLA [CLA Group - 20% CLA mixture (39.32 mole% c9,t11-CLA and 40.59 mole% t10,c12- CLA)], soybean oil + CLA (LA+CLA Group - 15.4% soybean oil and 4.6% CLA) or animal fat (AF, 20% lard). The CLA group showed lower weight gain and liver weight after refeeding, as well as increased serum cholesterol. The high dietary fat intake induced fat accumulation and an increase in ï¡-tocopherol in the liver, which were not observed in the CLA group. Circulating ï¡-tocopherol was increased in the CLA and CLA+LA groups. The high- fat diets reduced liver catalase activity. CLA isomers were incorporated into serum and tissues. In this shortterm refeeding experimental model, CLA prevented hepatic fat accumulation, although it produced an increase in serum cholesterol.
No hay consenso acerca de los efectos del ácido linoleico conjugado (CLA) sobre el metabolismo lipídico, especialmente en animales alimentados con una dieta alta en grasa. Por lo tanto, el objetivo del presente estudio fue evaluar la incorporación de isómeros de CLA en el suero, hígado y tejido adiposo, así como el estrés oxidativo generado en ratas realimentadas con dietas altas en grasa después de 48 horas de ayuno. Los animales fueron realimentados con dietas que contenían aceite de soja, rico en ácido linoleico [7% (Groupo Control - C)], o 20% (Groupo LA)], CLA [Groupo CLA - 20% de mezcla de CLA (39,32% moles del c9,t11-CLA y 40.59% moles del t10,c12-CLA)], aceite de soja + CLA (Grupo LA+- CLA - 15.4 % de aceite de soja y 4,6% de CLA) o grasa animal (Grupo AF, 20% de manteca de cerdo). El grupo CLA tuvo menor aumento de peso y menor peso hepático después de la realimentación, así como aumento del colesterol total em el suero. La dieta alta en grasa indujo la acumulación de grasa y un aumento de ï¡-tocoferol en el hígado, que no se observaron en el grupo CLA. El ï¡-tocoferol serico fue mayor en los grupos CLA y LA+CLA. Las dietas altas en grasa redujeron la actividad de la catalasa hepática. Isómeros de CLA fueron incorporados em el suero y tejidos. En este modelo de realimentación de corto prlazo, el CLA ha impedido la acumulación de grasa hepática, aunque genero un aumento del colesterol total sérico.
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Colesterol/sangre , Ácidos Grasos/sangre , Ácidos Linoleicos Conjugados/farmacología , Animales , Dieta Alta en Grasa , Ayuno/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratas , Ratas WistarRESUMEN
This work investigated the effects of Vitamin E (VE) on aberrant crypt foci (ACF) incidence, oxidative stress parameters (serum and hepatic VE concentration, and homocysteine, glutathione (GSH), and malondialdehyde (MDA) levels), and expression of both cyclooxygenase-2 (COX2) and proliferating cellular nuclear antigen (PCNA) in experimental colorectal carcinogenesis. Male Wistar rats received subcutaneous injections of 1,2-dimethylhydrazine (DMH) twice a week, for two weeks (40 mg/kg), except for the Control group. Animals were separated into groups that received different amounts of VE in the diet: 0 IU (0×), 75 IU (recommended daily intake, RDI), 225 IU (3× RDI), or 1500 IU (20× RDI), during (dDMH) or after (aDMH) administration of carcinogen. The 0×dDMH and 3×dDMH groups showed decreased serum VE levels. Hepatic VE concentration was higher in 3×aDMH as compared with the other groups. All the groups, except the Control and the 0×aDMH groups, had reduced GSH levels. The 0×dDMH, 0×aDMH, and 20×aDMH groups exhibited increased MDA levels. The aDMH groups had higher ACF incidence and PCNA expression. The 0×aDMH group presented higher ACF rate, followed by 20×aDMH. Moreover, the 3×aDMH group displayed reduced ACF incidence and COX2 expression. Multivariate analysis revealed that GSH modulated homocysteine levels and COX2. These results suggested that 1500 IU of VE is hazardous, whereas 225 IU of VE has beneficial effects on chemical colorectal carcinogenesis.
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Carcinogénesis/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Suplementos Dietéticos , Vitamina E/farmacología , 1,2-Dimetilhidrazina/administración & dosificación , 1,2-Dimetilhidrazina/toxicidad , Focos de Criptas Aberrantes/tratamiento farmacológico , Animales , Biomarcadores/sangre , Carcinógenos/administración & dosificación , Carcinógenos/toxicidad , Proliferación Celular/efectos de los fármacos , Neoplasias Colorrectales/inducido químicamente , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Regulación Neoplásica de la Expresión Génica , Glutatión/sangre , Homocisteína/sangre , Inmunohistoquímica , Masculino , Análisis Multivariante , Estrés Oxidativo/efectos de los fármacos , Antígeno Nuclear de Célula en Proliferación/genética , Antígeno Nuclear de Célula en Proliferación/metabolismo , Ratas , Ratas Wistar , Ingesta Diaria Recomendada , Aumento de Peso/efectos de los fármacosRESUMEN
BACKGROUND: The hepatopathy associated with short bowel syndrome (SBS) is a multifactorial disease associated with poor prognosis. Besides intestinal transplantation, no other treatment has been shown effective. The current study evaluated the efficacy of betaine for the treatment of hepatopathy associated with SBS. METHODS: A prospective, unicentric, non-placebo controlled trial was carried out. After initial evaluation, 10g of betaine anhydrous was administrated to SBS patients in two divided doses for three months. The hepatic steatosis was assessed through nuclear magnetic resonance (NMR), the inflammatory response by interleukin- 6 (IL-6), tumor necrosis factor-αï (TNF-α) and ferritin, besides the hepatic lesion through hepatic enzymes and bilirubin. Furthermore, the effect of betaine on homocysteine was evaluated as well as its safety and tolerability in this group of patients. RESULTS: After three months supplementation, patients showed decreased percentage of hepatic fat (p = 0.03) through triphasic NMR examination. There was no significant reduction of serum levels for inflammatory proteins and hepatic lesion markers. Homocysteinemia also did not present significant decrease. The most prevalent side effects were diarrhea and nausea, reported in 62% of the participants; however, these symptoms were transient and not severe enough to justify the treatment interruption. Parenteral nutrition-dependent patients did not present different hepatic lesion degree compared to patients who do not need the prolonged use of it. CONCLUSIONS: Betaine was shown to be a potential agent for the treatment of hepatopathy associated with SBS, which was evidenced by NMR, although the markers for hepatic lesion have not presented significant decrease.
Introducción: La hepatopatía asociada con el síndrome del intestino corto (SIC) es una enfermedad multifactorial asociada con un mal pronóstico. Además de trasplante intestinal, ningún otro tratamiento ha demostrado ser eficaz. El actual estudio evaluó la eficacia de la betaína para el tratamiento de la hepatopatía asociada a la SIC. Métodos: Fue realizado un estudio prospectivo, unicéntrico, no controlado con placeb. Después de la evaluación inicial, 10 g de betaína anhidra fue administrado a pacientes con SIC en dos dosis divididas durante tres meses. La esteatosis hepática se evaluó a través de resonancia magnética nuclear (RMN), la respuesta inflamatoria por la interleucina-6 (IL-6), factor de necrosis tumoral-ï¡ï (TNF-ï¡) y la ferritina, además de la lesión hepática por medio de enzimas hepáticas y de la bilirrubina. Además, el efecto de la betaína sobre la homocisteína fue evaluada así como su seguridad y tolerabilidad en este grupo de pacientes. Resultados: Después de la administración de la betaína por tres meses, los pacientes mostraron disminución de la porcentaje de grasa hepática (p = 0,03) demosntrado por examen de RMN trifásico. No hubo una reducción significativa de los niveles séricos de proteínas inflamatorias y marcadores de lesión hepática. La homocisteína también no presentó disminución significativa. Los efectos secundarios más frecuentes fueron diarrea y náuseas, presentado en 62% de los participantes, sin embargo, estos síntomas fueron transitorios y no lo suficientemente graves como para justificar la interrupción del tratamiento. Pacientes dependientes de nutrición parenteral no presentaron diferentes grados de lesión hepática en comparación con los pacientes que no necesitan el uso prolongado de la misma. Conclusiones: La betaína demostró ser un agente potencial para el tratamiento de la hepatopatía asociada a la SIC, que se evidenció mediante RMN, a pesar de los marcadores de lesión hepática no presentaron disminución significativa.
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Betaína/uso terapéutico , Fármacos Gastrointestinales/uso terapéutico , Hepatopatías/tratamiento farmacológico , Hepatopatías/etiología , Síndrome del Intestino Corto/complicaciones , Síndrome del Intestino Corto/terapia , Adulto , Anciano , Betaína/efectos adversos , Hígado Graso/etiología , Hígado Graso/prevención & control , Femenino , Fármacos Gastrointestinales/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
Dietary choline is required for proper structure and dynamics of cell membranes, lipoprotein synthesis, and methyl-group metabolism. In mammals, choline is synthesized via phosphatidylethanolamine N-methyltransferase (Pemt), which converts phosphatidylethanolamine to phosphatidylcholine. Pemt(-/-) mice have impaired VLDL secretion and developed fatty liver when fed a high-fat (HF) diet. Because of the reduction in plasma lipids, Pemt(-/-)/low-density lipoprotein receptor knockout (Ldlr(-/-)) mice are protected from atherosclerosis. The goal of this study was to investigate the importance of dietary choline in the metabolic phenotype of Pemt(-/-)/Ldlr(-/-) male mice. At 10-12 wk of age, Pemt(+/+)/Ldlr(-/-) (HF(+/+)) and half of the Pemt(-/-)/Ldlr(-/-) (HF(-/-)) mice were fed an HF diet with normal (1.3 g/kg) choline. The remaining Pemt(-/-)/Ldlr(-/-) mice were fed an HF diet supplemented (5 g/kg) with choline (HFCS(-/-) mice). The HF diet contained 60% of calories from fat and 1% cholesterol, and the mice were fed for 16 d. HF(-/-) mice lost weight and developed hepatomegaly, steatohepatitis, and liver damage. Hepatic concentrations of free cholesterol, cholesterol-esters, and triglyceride (TG) were elevated by 30%, 1.1-fold and 3.1-fold, respectively, in HF(-/-) compared with HF(+/+) mice. Choline supplementation normalized hepatic cholesterol, but not TG, and dramatically improved liver function. The expression of genes involved in cholesterol transport and esterification increased by 50% to 5.6-fold in HF(-/-) mice when compared with HF(+/+) mice. Markers of macrophages, oxidative stress, and fibrosis were elevated in the HF(-/-) mice. Choline supplementation normalized the expression of these genes. In conclusion, HF(-/-) mice develop liver failure associated with altered cholesterol metabolism when fed an HF/normal choline diet. Choline supplementation normalized cholesterol metabolism, which was sufficient to prevent nonalcoholic steatohepatitis development and improve liver function. Our data suggest that choline can promote liver health by maintaining cholesterol homeostasis.
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Colesterol/metabolismo , Colina/administración & dosificación , Dieta Alta en Grasa/efectos adversos , Hígado/efectos de los fármacos , Hígado/metabolismo , Animales , Ésteres del Colesterol/metabolismo , Hígado Graso/tratamiento farmacológico , Hígado Graso/etiología , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/patología , Masculino , Ratones , Ratones Noqueados , Enfermedad del Hígado Graso no Alcohólico , Fosfatidiletanolamina N-Metiltransferasa/sangre , Receptores de LDL/sangre , Triglicéridos/metabolismoRESUMEN
BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) is a metabolic disorder characterized by hepatic fat accumulation in the absence of alcohol consumption. Hyperhomocysteinemia is considered an independent risk factor for liver diseases, and the genetic polymorphisms C677T and A1298C in the MTHFR gene have been linked to hyperhomocysteinemia. The purpose of this study was to investigate serum homocysteine (Hcy) concentrations and the MTHFR C677T and A1298C polymorphisms as risk factors for the development of NAFLD. METHODS: One hundred and thirty-four Brazilian patients with biopsy-proven NAFLD and 134 healthy controls were recruited. The MTHFR C677T and A1298C polymorphisms were detected through polymerase chain reaction restriction fragment length polymorphism. Serum Hcy levels were determined by chemiluminescence. RESULTS: Serum Hcy levels were higher in NAFLD patients as compared to control subjects, but there were no differences between patients with steatosis and nonalcoholic steatohepatitis. The NAFLD and control groups did not differ in genotypic and allelic frequencies of the MTHFR C677T and A1298C polymorphisms, either. Elevated plasma Hcy levels were positively correlated with age in the NAFLD subjects. CONCLUSION: The MTHFR C677T and A1298C polymorphisms are not genetic risk factors for the development of NAFLD. Higher Hcy levels exist in NAFLD subjects, but they are not associated with liver disease severity.
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Hígado Graso/sangre , Hígado Graso/genética , Homocisteína/sangre , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Polimorfismo Genético , Adulto , Antropometría , Brasil , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Metilenotetrahidrofolato Reductasa (NADPH2)/metabolismo , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico , Reacción en Cadena de la Polimerasa , Factores de RiesgoRESUMEN
BACKGROUND/AIMS: Chronic alcoholism is characterized by hepatotoxicity associated with antioxidant and redox status imbalance. Continuous ethanol intake induces free radical synthesis, resulting in the depletion of antioxidants, especially α-tocopherol, which has an important role in lipid peroxidation. This study aimed to evaluate if α-tocopherol supplementation can restore liver phenotype in rats chronically exposed to ethanol. METHODS: α-Tocopherol levels were determined and histologic analysis of liver was performed. Hepatic gene expression was analyzed through oligonucleotide microarray and real-time PCR. RESULTS: Alcohol exposure for 6 weeks did not decrease hepatic α-tocopherol levels; however, both groups exposed to ethanol (supplemented or not with α-tocopherol) displayed fatty liver. The antioxidant supplementation prevented Mallory bodies and inflammatory infiltration, but not apoptosis, in liver of the rats exposed to ethanol. Gene expression analysis showed evidence of adaptive response to chronic alcohol consumption, where antioxidant components were not regulated. Nevertheless, differentially expressed genes reflected the change in cellular homeostasis. CONCLUSION: The hepatic α-tocopherol content was coherent with the antioxidant gene expression in this study. Cells are likely to have adapted and restored their antioxidant status after long-term ethanol exposure, which might be the reason for such conflicting reports concerning α-tocopherol status in chronic alcoholism.
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Etanol/toxicidad , Hígado/efectos de los fármacos , alfa-Tocoferol/administración & dosificación , Animales , Secuencia de Bases , Cromatografía Líquida de Alta Presión , Cartilla de ADN , Suplementos Dietéticos , Hígado/patología , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Ratas , Ratas Wistar , Reacción en Cadena en Tiempo Real de la Polimerasa , Espectrofotometría Ultravioleta , alfa-Tocoferol/farmacologíaRESUMEN
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) refers to the accumulation of hepatic steatosis in the absence of excess alcohol consumption. The pathogenesis of fatty liver disease and steatohepatitis (NASH) is not fully elucidated, but the common association with visceral obesity, hyperlipidemia, hypertension and type 2 diabetes mellitus (T2DM) suggests that it is the hepatic manifestation of metabolic syndrome. Peroxisome proliferator-activated receptor PPARα and PPARγ are members of a family of nuclear receptors involved in the metabolism of lipids and carbohydrates, adipogenesis and sensitivity to insulin. The objective of this study was to analyze the polymorphisms Leu162Val of PPARα and Pro12Ala of PPARγ as genetic risk factors for the development and progression of NAFLD. METHODS: One hundred and three NAFLD patients (89 NASH, 14 pure steatosis) and 103 healthy volunteers were included. Single nucleotide polymorphisms (SNPs) Leu162Val and Pro12Ala were analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). RESULTS: NASH patients presented higher BMI, AST and prevalence of T2DM than patients with pure steatosis. A higher prevalence of 12Ala allele was observed in the NASH Subgroup when compared to Control Group. When we grouped NASH and Steatosis Subgroups (NAFLD), we found lower serum glucose and more advanced fibrosis in the Leu162Val SNP. On the other hand, there was no statistical difference in clinical, laboratorial and histological parameters according to the Pro12Ala SNP. CONCLUSIONS: We documented a lower prevalence of 12Ala allele of gene PPARγ in the NASH Subgroup when compared to Control Group. In NAFLD patients, there were no associations among the occurrence of Pro12Ala SNP with clinical, laboratorial and histological parameters. We also documented more advanced fibrosis in the Leu162Val SNP. The obtained data suggest that Pro12Ala SNP may result in protection against liver injury and that Leu162Val SNP may be involved in the progression of NAFLD.
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Hígado Graso/genética , PPAR alfa/genética , PPAR gamma/genética , Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo de Nucleótido Simple , Adulto , Brasil , Estudios de Casos y Controles , Femenino , Estudios de Asociación Genética , Humanos , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no AlcohólicoRESUMEN
BACKGROUND: Down syndrome (DS) results from the presence and expression of three copies of the genes located on chromosome 21. Studies have shown that, in addition to overexpression of the Cystathionine ß-synthase (CBS) gene, polymorphisms in genes involved in folate/homocysteine (Hcy) metabolism may also influence the concentrations of metabolites of this pathway. AIM: Investigate the association between Dihydrofolate reductase (DHFR) 19-base pair (bp) deletion and Serine hydroxymethyltransferase (SHMT) C1420T polymorphisms and serum folate and plasma Hcy and methylmalonic acid (MMA) concentrations in 85 individuals with DS. METHODS: Molecular analysis of the DHFR 19-bp deletion and SHMT C1420T polymorphisms was performed by polymerase chain reaction (PCR) by difference in the size of fragments and real-time PCR allelic discrimination, respectively. Serum folate was quantified by chemiluminescence and plasma Hcy and MMA by liquid chromatography-tandem mass spectrometry. RESULTS: Individuals with DHFR DD/SHMT TT genotypes presented increased folate concentrations (p=0.004) and the DHFR II/SHMT TT genotypes were associated with increased MMA concentrations (p=0.008). In addition, the MMA concentrations were negatively associated with age (p=0.04). CONCLUSION: There is an association between DHFR DD/SHMT TT and DHFR II/SHMT TT combined genotypes and folate and MMA concentrations in individuals with DS.
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Síndrome de Down/genética , Ácido Fólico/metabolismo , Eliminación de Gen , Glicina Hidroximetiltransferasa/genética , Homocisteína/sangre , Ácido Metilmalónico/sangre , Polimorfismo Genético , Tetrahidrofolato Deshidrogenasa/genética , Adolescente , Adulto , Niño , Preescolar , Síndrome de Down/sangre , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Lactante , Masculino , Adulto JovenRESUMEN
The objective of this study was to evaluate the vitamin status, inflammatory markers, and oxidative stress markers in adult patients up to 3 days after thermal injury. This prospective study was conducted with 11 patients 24 to 72 hours after thermal injury (Burn Group), total surface area ranging from 10 to 41%, 34.3 ± 9.3 years, 82% of males, body mass index of 22.3 ± 2.9 kg/m(2). We included 11 healthy adults (Control Group), 36.5 ± 7.6 years, 73% of males, and body mass index of 23.8 ± 2.5 kg/m(2). Laboratory data were measured (plasma total protein, albumin, transferrin, lymphocyte counts, zinc, and iron), as well as serum vitamins (folic acid, vitamin B12, and vitamins A, C, and E), inflammatory stress markers (C-reactive protein, ferritin, and acid α1-glycoprotein) and oxidative stress markers such as glutathione peroxidase (GPx) and thiobarbituric acid reactive substances. The inflammatory stress was characterized by lower levels of total protein (median difference 1.2 g/dL, 95% CI: 0.4-2.1) and albumin (median difference 0.9 g/dL, 95% CI: 0.5-1.5), and higher levels of C-reactive protein (median difference -8.12 mg/dL, 95% CI: -11.62 to 4.61) and α-1 glycoprotein acid (median difference -28.56 mg/dL, 95% CI: -51.57 to -5.07) in burn patients. Decreased serum levels of vitamin A (median difference 1.10 µmol/L, 95% confidence interval [CI]: 0.42-1.66) and vitamin C (median difference 0.82 mg/dL, 95% CI: 0.50-1.04) were also detected. There was no statistical evidence of difference in the serum levels of glutathione peroxidase and thiobarbituric acid reactive substances between burn patients and controls, respectively. Even though there is an inflammatory stress, the obtained data showed that oxidative stress markers are normal 24 to 72 hours after burn injury. The decrease in negative acute phase protein may account for the diminished serum levels of vitamin A, which seems to be related to inflammatory stress. The marked decrease in the serum levels of vitamin C can be justified by augmented cutaneous loss and consumption in the regeneration of vitamin E.