Long-Term Exogenous Melatonin Treatment Modulates Overall Feed Efficiency and Protects Ovarian Tissue Against Injuries Caused by Ethanol-Induced Oxidative Stress in Adult UChB Rats

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

Differential morphofunctional characteristics and gene expression in fast and slow muscle of rats with monocrotaline-induced heart failure

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

Growth hormone and heart failure: Oxidative stress and energetic metabolism in rats

Several evidences point for beneficial effects of growth hormone (GH) in heart failure (HF). Taking into account that HF is related with changes in myocardial oxidative stress and in energy generation from metabolic pathways, it is important to clarify whether GH increase or decrease myocardial oxidative stress and what is its effect on energetic metabolism in HF condition. Thus, this study investigated the effects of two different doses of GH on energetic metabolism and oxidative stress in myocardium of rats with HF. Male Wistar rats (n = 25) were submitted to aortic stenosis (AS). The HF was evidenced by tachypnea and echocardiographic criteria around 28 weeks of AS. The rats were then randomly divided into three groups: (HF) with HF, treated with saline (0.9% NaCl); (HF-GHI), treated with 1 mk/kg/day recombinant human growth hormone (rhGH), and (HF-GH2) treated with 2 mg/kg/day rhGH. GH was injected, subcutaneously, daily for 2 weeks. A control group (sham; n = 12), with the same age of the others rats was evaluated to confirm data for AS. HF had lower IGF-I (insulin-like growth factor-I) than sham-operated rats, and both GH treatments normalized IGF-I level. HF-GH1 animals had lower lipid hydroperoxide (LH), LH/total antioxidant substances (TAS) and glutathione-reductase than HF. Glutathione peroxidase (GSH-Px), hydroxyacyl coenzyme-A dehydrogenase, lactate dehydrogenase(LDH) were higher in HF-GH1 than in HF. HF-GH2 compared with HF, had increased LH/TAS ratio, as well as decreased oxidized glutathione and LDH activity. Comparing the two GH doses, GSH-Px, superoxide dismutase and LDH were lower in HF-GH2 than in HF-GHI. In conclusion, GH effects were dose-dependent and both tested doses did not aggravate the heart dysfunction. The higher GH dose, 2 mg/kg exerted detrimental effects related to energy metabolism and oxidative stress. The lower dose, 1 mg/kg GH exerted beneficial effects enhancing antioxidant defences, reducing oxidative stress and improving energy generation in myocardium of rats with heart failure. (c) 2007 Elsevier Ltd. All rights reserved.

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.

Measurement of gastric contraction activity in dogs by means of AC biosusceptometry

The mechanical nature of gastric contraction activity (GCA) plays an important role in gastrointestinal motility. The aim of this study was to detect GCA in anaesthetized dogs, using simultaneously the techniques of AC biosusceptometry (ACB) and manometry, analysing the characteristics of frequency and amplitude (motility index) of GCA, modified by drugs such as prostigmine and N-butyl-scopolamine. The ACB method is based on a differential transformer of magnetic flux and the magnetic tracer works as a changeable external nucleus. This magnetic tracer causes a modification in the magnetic flux, which is detected by the coils. The results obtained from the ACB showed a performance comparable to the manometry in measuring the modifications in the frequency and amplitude of the GCA. We concluded that this ACB technique, non-invasive and free of ionizing radiation, is an option for evaluating GCA and can be employed in future clinical studies.

Hypoglycaemic and antioxidant effects of onion, Allium cepa: dietary onion addition, antioxidant activity and hypoglycaemic effects on diabetic rats

The purpose of the present study was to discover the relative potency of onion, Allium cepa, with respect to its hypoglycaemic and hypolipidaemic effects on the diabetic situation, and the association of these effects with the potential against oxidative stress. Male Wistar rats were divided into four groups. A normal control ( group A), and a non-diabetic group ( group B) were treated daily with 1 ml A. cepa solution (0.4 g A. cepa/rat). Groups C and D were made diabetic by an intraperitoneal injection of streptozotocin (STZ) ( 60 mg/kg body weight) in citrate buffer ( pH 6.3). These animals ( groups C and D) were the STZ diabetic control and STZ diabetic rats with onion intake, respectively. Onion increased the fasting serum high-density lipoprotein levels, and demonstrated alleviation of hyperglycaemia in STZ diabetic rats. The hypoglycaemic and hypolipidaemic actions of A. cepa were associated with antioxidant activity, since onion decreased superoxide dismutase activities while no increased lipid hydroperoxide and lipoperoxide concentrations were observed in diabetic rats treated with A. cepa.

Tobacco Smoke Induces Ventricular Remodeling Associated with an Increase in NADPH Oxidase Activity

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Ventricular Remodeling Induced by Tissue Vitamin A Deficiency in Rats

Background/Aims: Experimental studies suggest that vitamin A plays a role in regulating cardiac structure and function. We tested the hypothesis that cardiac vitamin A deficiency is associated with adverse myocardial remodeling in young adult rats. Methods: Two groups of young female rats, control (C - n = 29) and tissue vitamin A deficient (RVA - n = 31), were subjected to transthoracic echocardiography exam, isolated rat heart study and biochemical study. Results: The RVA rats showed a reduced total vitamin A concentration in both the liver and heart [vitamin A in heart, mu mol/kg (C = 0.95 +/- 0.44 and RVA = 0.24 +/- 0.16, p = 0.01)] with the same serum retinol levels (C = 0.73 +/- 0.29 mu mol/L e RVA = 0.62 +/- 0.17 mu mol/L, p = 0.34). The RVA rats showed higher left ventricular diameters and reduced systolic function. The RVA rats also demonstrated increased lipid hydroperoxide/total antioxidant capacity ratio and cardiac levels of IFN-gamma and TNF-alpha but not of metalloproteinase (MMP)-2 and -9 activity. on the other hand, the RVA rats had decreased levels of beta-hydroxyacylcoenzyme A dehydrogenase and lactate dehydrogenase. Conclusions: Tissue vitamin A deficiency stimulated cardiac remodeling and ventricular dysfunction. Additionally, the data support the involvement of oxidative stress, energy metabolism, and cytokine production in this remodeling process. Copyright (C) 2010 S. Karger AG, Basel

Effects of ginger (Zingiber officinale Roscoe) on DNA damage and development of urothelial tumors in a mouse bladder carcinogenesis model

Extracts of the spice ginger (Zingiber officinale Roscoe) are rich in gingerols and shogaols, which exhibit antioxidant, anti-inflammatory, antifungal, anti mycobacterial, and anticarcinogenic proprieties. The present study evaluated the chemoprotective effects of a ginger extract on the DNA damage and the development of bladder cancer induced by N-butyl-N-(4-hydroxibutyl) nitrosamine (BBN)/N-methyl-N-nitrosourea (MNU) in male Swiss mice. Groups G1-G3 were given 0.05% BBN in drinking water for 18 weeks and four i.p. injections of 30 mg/kg body weight MNU at 1, 3, 10, and 18 weeks. Group G4 and G5 received only the BBN or MNU treatments, respectively, and groups G6 and G7 were not treated with BBN or MNU. Additionally, Groups G2, G3, and G6 were fed diets containing 1, 2, and 2% ginger extract, respectively, while Groups G1, G4, G5, and G7 were fed basal diet. Samples of peripheral blood were collected during the experiment for genotoxicity analysis; blood collected 4 hr after each MNU dose was used for the analysis of DNA damage with the Comet assay (assay performed on leukocytes from all groups), while reficulocytes collected 24 hr after the last MNU treatment of Groups G5-G7 were used for the micronucleus assay. At the end of the experiment, the urinary bladder was removed, fixed, and prepared for histopathological, cell proliferation, and apoptosis evaluations. Ginger by itself was not genotoxic, and it did not alter the DNA damage levels induced by the BBN/MNU treatment during the course of the exposure. The incidence and multiplicity of simple and nodular hyperplasia and transitional cell carcinoma (TCC) were increased by the BBN/MNU treatment, but dietary ginger had no significant effect on these responses. However, in Group G2 (BBN/MNU/2% ginger-treated group), there was an increased incidence of Grade 2 TCC. The results suggest that ginger extract does not inhibit the development of BBN-induced mouse bladder tumors.

Beneficial effects of dietary copper supplementation on serum lipids and antioxidant defenses in rats

Background: A nutrition experiment was utilized to investigate the effects of two levels of dietary copper (Cu) supplementation on lipid profile and antioxidant defenses in serum of rats. Methods: Male Wistar rats (180-200 g; n = 10) were divided into three groups: control group (A), fed a basal diet with 6 mu g Cu/g, and rats fed a basal diet with Cu (CuSO4) supplementation from aqueous solutions, for 4 weeks at the final concentrations of 2 mg Cu/rat (B) and 3 mg Cu/rat (C). Results: No significant changes were observed in final body weight, body weight gain, food consumption, total serum protein and high-density lipoprotein. Cu supplementation reduced the triacylglycerol (TG), total cholesterol and low-density lipoprotein (LDL-C). The LDL-C/TG ratio and total antioxidant substances (TAS) were higher in (B) and (C) groups than in (A) group. There was a positive correlation between Cu supplementation and ceruloplasmin levels. The markers of oxidative stress, lipid hydroperoxide and lipoperoxide were decreased with Cu supplementation. No alterations were observed in superoxide dismutase, indicating saturation of Cu enzyme site. The glutathione peroxidase activities (GSH-Px) were increased in both Cu-supplemented groups. Considering that a copper-selenium interaction can affect mineral availability of both elements, the effects of Cu on TAS and GSH-Px activities were associated with increased selenium disposal. Conclusions: Dietary Cu supplementation had beneficial effects on lipid profile by improving endogenous antioxidant defenses and decreasing the oxidative stress in vivo. Copyright (C) 2005 S. Karger AG, Basel.

Interaction of hypercaloric diet and physical exercise on lipid profile, oxidative stress and antioxidant defenses

The present study examined the interaction of hypercaloric diet (HD) and physical exercise on lipid profile and oxidative stress in serum and liver of rats. Male Wistar rats (60-days-old) were fed with a control (C) and hypercaloric diet (H). Each of the two dietary groups (C and H) was divided into three subgroups (n = 8), sedentary (CS and HS), exercised 2 days a week (CE2 and HE2) and exercised 5 days a week (CE5 and HE5). The swimming was selected as a model for exercise performance. After 8-weeks exercised rats showed decreased lactate dehydrogenase serum activities, demonstrating the effectiveness of the swimming as an aerobic-training protocol. Exercise 5-days a week reduced the body weight gain. Triacylglycerol (TG) and very low-density lipoprotein (VLDL-C) were increased in HD-fed rats. HE5 and CE5 rats had decreased TG, VLDL-C and cholesterol. HE2 rats had enhanced high-density lipoprotein (HDL-C) in serum. No alterations were observed in lipid hydroperoxide (LH), while total antioxidant substances (TAS) were increased in serum of exercised rats. HD-fed rats had hepatic TG accumulation. Superoxide dismutase activities were increased and catalase was decreased in liver of exercised rats. The interaction of HD and physical exercise reduced TAS and enhanced LH levels in hepatic tissue. In conclusion, this study confirmed the beneficial effect of physical exercise as a dyslipidemic-lowering component. Interaction of HD and physical exercise had discrepant effects on serum and liver oxidative stress. The interaction of HID and physical exercise reduced the oxidative stress in serum. HD and physical exercise interaction had pro-oxidant effect on hepatic tissue, suggesting that more studies should be done before using physical exercise as an adjunct therapy to reduce the adverse effects of HD. (c) 2006 Elsevier Ltd. All rights reserved.

Toxicity of copper intake: lipid profile, oxidative stress and susceptibility to renal dysfunction

The present study was carried out to investigate the effects of copper (Cu) intake on lipid profile, oxidative stress and tissue damage in normal and in diabetic condition. Since diabetes mellitus is a situation of high-risk susceptibility to toxic compounds, we examined potential early markers of Cu excess in diabetic animals. Male Wistar rats, at 60-days-old were divided into six groups of eight rats each. The control(C) received saline from gastric tube, the no-diabetic(Cu-10), treated with 10 mg/kg of Cu(Cu(++)-CuSO(4), gastric tube), no-diabetic with Cu-60mg/kg(Cu-60), diabetic(D), diabetic low-Cu(DCu-10) and diabetic high-Cu(DCu-60). Diabetes was induced by an ip injection of streptozotocin (60mg/kg). After 30 days of treatments, no changes we're observed in serum lactate dehydrogenase, alanine transaminase and alkaline phosphatase; indicating no adverse effects on cardiac and hepatic tissues. D-rats had glucose intolerance and dyslipidemic profile. Cholesterol and LDL-cholesterol were higher in Cu-60 and DCu-60 than in C, Cu-10 and D and DCu-10 groups respectively. Cu-60 rats had higher lipid hydroperoxide (HP) and lower superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) serum activities than C and Cu-10 rats. LH was increased and GSH-Px was decreased, while no alterations were observed in SOD and catalase in serum of DCu-60 animals. DCu-60 rats had increased urinary glucose, creatinine and albumin. In conclusion, Cu intake at high concentration induced adverse effects on lipid profile, associated with oxidative stress and diminished activities of antioxidant enzymes. Diabetic animals were more susceptible to copper toxicity. High Cu intake induced dyslipidemic profile, oxidative stress and kidney dysfunction in diabetic condition. Copper renal toxicity was associated with oxidative stress and reduction at least, one of the antioxidant enzymes. (C) 2004 Elsevier Ltd. All rights reserved.

Evaluation of lipid profile and oxidative stress in STZ-induced rats treated with antioxidant vitamin

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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)