Chronic ethanol intake promotes double gluthatione S-transferase transforming growth factor-alpha-positive hepatocellular lesions in male Wistar rats

The chronic ethanol intake influence on the gluthatione S-transferase (GST-P) and transforming growth factor alpha (TGF-alpha) expression in remodeling/persistent preneoplastic lesions (PNLs) was evaluated in the resistant hepatocyte model. Male Wistar rats were allocated into five groups: G1, non-treated, fed water and chow ad libitum; G2, non-treated and pair-fed chow (restricted to match that of G3 group) and a maltodextrin (MD) solution in tap water (matched ethanol-derived calories); G3, fed 5% ethanol in drinking water and chow ad libitum; G4, diethylnitrosamine (DEN, 200 mg/kg, body weight) plus 200 parts per million of 2-acetylaminofluorene (2-AAF) for 3 weeks and pair-fed chow (restricted to match that of G5 group) and an MD solution in tap water (matched ethanol-derived calories); G5, DEN/2-AAF treatment, fed ethanol 5% and chow ad libitum. All animals were subjected to 70% partial hepatectomy at week 3 and sacrificed at weeks 12 or 22, respectively. Liver samples were collected for histological analysis or immunohistochemical expression of GST-P, TGF-alpha and proliferating cell nuclear antigen or zymography for matrix metalloproteinases-2 and -9. At the end of ethanol treatment, there was a significant increase in the percentage of liver area occupied by persistent GST-P-positive PNLs, the number of TGF-alpha-positive PNLs and the development of liver tumors in ethanol-fed and DEN/2-AAF-treated groups (G5 versus G4, P < 0.001). In addition, ethanol feeding led to a significant increase in cell proliferation mainly in remodeling and persistent PNLs with immunoreactivity for TGF-alpha at week 22 (P < 0.001). Gelatinase activities were not altered by ethanol treatment. The results demonstrated that ethanol enhances the selective growth of PNL with double expression of TGF-alpha and GST-P markers.

Morphological changes on the hard palatine mucosa of rats (Rattus norvegicus albinus) after chronic alcohol consumption

In order to examine the effects of alcohol on the hard palatine mucosa of rats, sixty adult female rats (Rattus norvegicus albinus) were divided into two experimental groups. The control group received solid diet (Purina rat chow) and tap water ad libitum. The alcoholic group received the same solid diet and was allowed to drink only sugar cane brandy dissolved in 30% Gay Lussac (v/v). At the end of periods of 90, 180 and 270 days of treatment, the animals at estro were sacrificed and the hard palatine mucosa were prepared for TEM and SEM methods. The basal cells of the alcoholic groups (90, 180 and 270 days of treatment) demonstrated some alterations: the intercellular spaces between these cells were higher, presented cytoplasmatic lipid droplets and autolysis. Also, the connective tissue showed intense lipid droplets accumulation in the alcoholic groups. These modifications suggested that chronic alcohol ingestion was able to modify the integrity of the cells in the rat hard palatine mucosa.

Differential nutritional, endocrine, and cardiovascular effects in obesity-prone and obesity-resistant rats fed standard and hypercaloric diets

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Diet compounds, glycemic index and obesity-related cardiac effects

Background: Diet compounds may influence obesity-related cardiac oxidative stress and metabolic sifting. Carbohydrate-rich diet may be disadvantageous from fat-rich diet to cardiac tissue and glycemic index rather than lipid profile may predict the obesity-related cardiac effects.Materials and methods: Male Wistar rats were divided into three groups (n=8/group): (C) receiving standard chow (3.0 kcal/g); (CRD) receiving carbohydrate-rich diet (4.0 kcal/g), and (FRD) receiving fat-rich diet (4.0 kcal/g). Rats were sacrificed after the oral glucose tolerance test (OGTT) at 60 days of dietary treatments. Lipid profile and oxidative stress parameters were determined in serum. Myocardial samples were used to determine oxidative stress, metabolic enzymes, glycogen and triacylglycerol.Results: FRD rats showed higher final body weight and body mass index than CRD and C. Serum cholesterol and low-density lipoprotein were higher in FRD than in CRD, while triacylglycerol and oxidized low-density lipoprotein cholesterol were higher in CRD than in FRD. CRD rats had the highest myocardial lipid hydroperoxide and diminished superoxide dismutase and catalase activities. Myocardial glycogen was lower and triacylglycerol was higher in CRD than in C and FRD rats. Although FRD rats had depressed myocardial-reducing power, no significant changes were observed in myocardial energy metabolism. Myocardial beta-hydroxyacyl coenzyme-A dehydrogenase and citrate synthase, as well as the enhanced lactate debydrogenase/citrate synthase ratio indicated that fatty acid degradation was decreased in CRD rats. Glycemic index was positively correlated with obesity-related cardiac effects.Conclusions: Isoenergetic carbohydrate-rich and fat-rich diets induced different degree of obesity and differently affected lipid profile. Carbohydrate-rich diet was deleterious relative to fat-rich diet in the heart enhancing lipoperoxidation and shifting the metabolic pathway for energy production. Glycemic index rather than dyslipidemic profile may predict the obesity effects on cardiac tissue. (C) 2007 Elsevier B.V. All rights reserved.

Dieta hiperlipídica com farinha de soja como fonte proteica: utilização na seleção de ratos propensos e resistentes à obesidade

OBJETIVO: Desenvolver uma dieta hiperlipídica de baixo custo, tendo farinha de soja como fonte proteica, que seja eficiente na seleção de ratos propensos e resistentes à obesidade e que permita alcançar fenótipo obeso nos animais propensos. Além desses requisitos, a dieta deve ser palatável e não rejeitada a curto prazo pelo animal. MÉTODOS: A dieta proposta foi obtida misturando-se leite condensado (15,5%), amendoim (18,5%), farinha de soja (20,0%), óleo de milho (6,0%), ração Bio Tec (30,0%) e bolacha wafer de chocolate (10,0%). A mistura foi peletizada e submetida à análise bromatológica. A dieta foi ofertada a ratos Wistar durante uma semana; posteriormente, os animais foram divididos em três grupos, de acordo com o ganho de peso. O terço superior foi considerado propenso à obesidade e o terço inferior, resistente à obesidade. Após 80 dias de oferta da dieta, os animais foram sacrificados e foram quantificados o peso corpóreo, consumo alimentar, gorduras retroperitoneal, periepididimal, de carcaça e gorduras totais. RESULTADOS: Verificou-se que a dieta apresentava 5,31kcal/g, com a seguinte composição: 22,3% de gordura, 22,2% de proteína, 15,9% de fibra, estimando-se 35,7% de carboidrato. Ratos propensos à obesidade, alimentados por 87 dias com a dieta hipercalórica, apresentaram peso corpóreo, gorduras retroperitoneal, periepididimal e totais significativamente maiores do que animais resistentes à obesidade (p<0,05). O consumo de alimentos também foi maior em animais propensos (p<0,05). Verificou-se também que a substituição da caseína pela farinha de soja, como componente proteico da ração, levou à diminuição de 96,0% no custo do estudo. CONCLUSÃO: A dieta formulada com farinha de soja apresentou custo reduzido e foi capaz de desenvolver o fenótipo obeso em ratos propensos, à semelhança do observado na literatura com outras dietas.

In utero protein restriction causes growth delay and alters sperm parameters in adult male rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of N-acetylcysteine on sucrose-rich diet-induced hyperglycaemia, dyslipidemia and oxidative stress in rats

This study examined whether sucrose-rich diet (SRD)-induced hyperglycaemia, dyslipidemia and oxidative stress may be inhibited by N-acetylcysteine (C5H9-NO3S), an organosulfur from Allium plants. Male Wistar 40 rats were divided into four groups (n = 10): (C) given standard chow and water; (N) receiving standard chow and 2 mg/l N-acetylcysteine in its drinking water; (SRD) given standard chow and 30% sucrose in its drinking water; and (SRD-N) receiving standard chow, 30% sucrose and N-acetylcysteine in its drinking water. After 30 days of treatment, SRD rats had obesity with increased abdominal circumference, hyperglycaemia, by dyslipidemia and hepatic triacylglycerol accumulation. These adverse effects were associated with oxidative stress and depressed lipid degradation in hepatic tissue. The SRD adverse effects were not observed in SDR-N rats. N-Acetylcysteine reduced the oxidative stress, enhancing glutathione-peroxidase activity, and normalizing lipid hydroperoxyde, reduced glutathione and superoxide dismutase in hepatic tissue of SRD-N rats. The beta-hydroxyacyl coenzyme-A dehydrogenase and citrate-synthase activities were increased in SRD-N rats, indicating enhanced lipid degradation in hepatic tissue as compared to SRD. SRD-N rats had reduced serum oxidative stress and diminished glucose, triacylglycerol, very-low-density lipoprotein (VLDL), oxidized low-density lipoprotein (alpha-LDL) and cholesterol/highdensity lipoprotein (HDL) ratio in relation to SRD. In conclusion, NAC offers promising therapeutic values in prevention of dyslipidemic profile and alleviation of hyperglycaemia in high-sucrose intake condition by improving antioxidant defences. N-Acetylcysteine had also effects preventing metabolic shifting in hepatic tissue, thus enhancing fat degradation and reducing body weight gain in conditions of excess sucrose intake. The application of this agent in food system via exogenous addition may be feasible and beneficial for antioxidant protection. (c) 2006 Elsevier B.V All rights reserved.

Effects of N-acetylcysteine on alcohol abstinence and alcohol-induced adverse effects in rats

Alcoholism is rampant in modern society and some antioxidant compound could perhaps be useful to reduce the damage done by alcohol consumption and abstinence. The present study was undertaken to investigate the association of N-acetylcysteine (NAC) intake, alcoholism, and alcohol abstinence on lipid profile, in vivo low-density lipoprotein (LDL) oxidation, oxidative stress, and antioxidant status in serum and liver of rats. Initially, male Wistar 30 rats were divided into two groups: (C, N = 6) given standard chow and water; (E, N = 24) receiving standard chow and aqueous ethanol solution in semi-voluntary research. After 30 days of ethanol exposure, (E) group was divided into four subgroups (N = 6/group): (E-E) continued drinking 30% ethanol solution; (E-NAC) drinking ethanol solution containing 2 g/L NAC (AB) changed ethanol solution to water; (AB-NAC) changed ethanol to aqueous solution 2 g/L NAC. After 15 days of the E-group division, E-E rats had higher serum alanine transaminase, lower body weight, and surface area, despite higher energy intake than C. E-E rats had also lower feed efficiency, dyslipidemia with enhanced triacyl glycerol, very low-density lipoprotein (VLDL), lipid hydroperoxide (LH) and in vivo oxidized-LDL (ox-LDL). AB, E-NAC, and AB-NAC rats ameliorated serum oxidative stress markers and normalized serum lipids. E-E rats had higher hepatic LH and lower reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio than C, indicating hepatic oxidative stress. AB and E-NAC rats normalized hepatic LH, GSSG, and the GSH/GSSG ratio, compared to E-E. AB-NAC rats had the lowest serum ox-LDL, hepatic LH levels, and the highest GSH reductase activity in hepatic tissue. In conclusion, the present study brought new insights into alcohol consumption, because ethanol exposure enhanced serum in vivo ox-LDL, as well as serum and hepatic oxidative stress. N-acetylcysteine offers promising therapeutic value to inhibit ethanol-induced adverse effects. Ethanol withdrawal had beneficial effects on serum lipids, but was more effective when coupled with NAC supplementation. Ethanol abstinence and NAC intake interact synergistically, improving serum lipids and hepatic antioxidant defenses. (c) 2009 Elsevier B.V. All rights reserved.

Alcoholism and alcohol abstinence: N-acetylcysteine to improve energy expenditure, myocardial oxidative stress, and energy metabolism in alcoholic heart disease

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

N-acetylcysteine in high-sucrose diet-induced obesity: Energy expenditure and metabolic shifting for cardiac health

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

N-Acetylcysteine an Allium Plant Compound Improves High-Sucrose Diet-Induced Obesity and Related Effects

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Alterações bioquímicas e hepáticas em ratos submetidos à uma dieta hiperlipídica/hiperenergética

OBJETIVO: O presente estudo teve como objetivo analisar as alterações bioquímicas hepáticas decorrentes da administração de uma dieta hiperlipídica/hiperenergética em ratos. MÉTODOS: Foram utilizados 20 ratos (Wistar) com 90 dias de idade divididos em dois grupos, grupo-controle constituída por ratos eutróficos alimentados com dieta comercial para roedores e grupo-dieta constituída por ratos submetidos a uma dieta hiperlipídica/hiperenergética semi purificada feita com 35% de gordura sendo 31% de origem animal a qual possui 39% de gordura saturada e 4% de origem vegetal (óleo de soja). Os animais do grupo-controle foram mantidos com dieta comercial Purina® e o grupo-dieta com uma dieta hiperlipídica/hiperenergética constituída por 35% de gordura. Após 60 dias de administração de uma dieta hiperlipídica/hiperenergética, analisou-se massa corporal, sensibilidade à insulina, concentração sérica de glicose, insulina e ácidos graxos livres e medida do nível de triglicerídeos, lipídeos totais e atividade lipogênica hepática. RESULTADOS: O grupo-dieta apresentou maior massa corporal e resistência à insulina. No sangue não foram encontradas diferenças entre os grupos para os níveis de glicose. Foi evidenciada maior concentração de insulina e de ácidos graxos livres no soro para o grupo-dieta. No fígado o nível de lipídeos totais, triglicerídeos e taxa lipo-gênica foram superiores às do grupo-controle. CONCLUSÃO: Portanto, nossos achados demonstram que dois meses de ingestão de dieta hiperlipídica/hiperenergética por ratos adultos eleva o peso corporal, ácidos graxos livres hepáticos, diminui a sensibilidade à insulina, demostrando sinais típicos de doença hepática gordurosa não-alcoólica.

High-fat diet associated with obesity induces impairment of mouse corpus cavernosum responses

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Platelet hyperaggregability in high-fat fed rats: A role for intraplatelet reactive-oxygen species production

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Integrable NLS equation with time-dependent nonlinear coefficient and self-similar attractive BEC

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)