Soy beta-Conglycinin (7S Globulin) Reduces Plasma and Liver Cholesterol in Rats Fed Hypercholesterolemic Diet

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Influence of a hypercholesterolemic diet on the collagen composition of the bladder wall extracellular matrix in rats

Purpose: To investigate the effects of hypercholesterolemic diet on the collagen composition of urinary bladder wall. Materials and methods: Forty-five female 4-week-old Wistar rats were divided into three groups: 1) control group fed a normal diet (ND); 2) model of bladder outlet obstruction (BOO) group fed a ND; and 3) group fed a HCD (1.25% cholesterol). Total serum cholesterol, LDL cholesterol and body weight were assessed at baseline. Four weeks later, group 2 underwent a surgical procedure resulting in a partial BOO, while groups 1 and 3 underwent a sham similar surgical procedure. Six weeks later, all animals had their bladders removed; serum cholesterol and LDL cholesterol levels and body weights were measured. Morphological and morphometric analysis was performed by Picrosirius staining and collagen types I and III were identified by immunofluorescence. Statistical analysis was completed and significance was considered when p<0.05. Results: Rats fed an HCD exhibited a significant increase in LDL cholesterol levels (p<0.001) and body weight (p=0.017), when compared to the groups fed a ND during the ten-week study period. Moreover, the HCD induced morphological alterations of the bladder wall collagen, regarding thin collagen fibers and the amounts of type III collagen when compared to the control group (p=0.002 and p=0.016, respectively), resembling the process promoted in the BOO model. Conclusions: A hyper-cholesterolemic diet in Wistar rats promoted morphological changes of the bladder types of collagen, as well as increases in body weight and LDL cholesterol.

Adhesion molecules of detrusor muscle cells are influenced by a hypercholesterolemic diet or bladder outlet obstruction in a wistar rat model

Abstract Background Cell adhesion molecules (CAMs) are essential for maintaining tissue integrity by regulating intercellular and cell to extracellular matrix interactions. Cadherins and catenins are CAMs that are located on the cell membrane and are important for adherens junction (AJ) function. This study aims to verify if hypercholesterolemic diet (HCD) or bladder outlet obstruction (BOO) promotes structural bladder wall modifications specific to alterations in the expression of cadherins and catenins in detrusor muscle cells. Methods Forty-five 4-week-old female Wistar rats were divided into the following three groups: group 1 was a control group that was fed a normal diet (ND); group 2 was the BOO model and was fed a ND; and group 3 was a control group that was fed a HCD (1.25% cholesterol). Initially, serum cholesterol, LDL cholesterol and body weight were determined. Four weeks later, groups 1 and 3 underwent a sham operation; whereas group 2 underwent a partial BOO procedure that included a suture tied around the urethra. Six weeks later, all rats had their bladders removed, and previous exams were repeated. The expression levels of N-, P-, and E-cadherin, cadherin-11 and alpha-, beta- and gamma-catenins were evaluated by immunohistochemistry with a semiquantitative analysis. Results Wistar rats fed a HCD (group 3) exhibited a significant increase in LDL cholesterol levels (p=0.041) and body weight (p=0.017) when compared to both groups that were fed a normal diet in a ten-week period. We found higher β- and γ-catenin expression in groups 2 and 3 when compared to group 1 (p = 0.042 and p = 0.044, respectively). We also observed Cadherin-11 overexpression in group 3 when compared to groups 1 and 2 (p = 0.002). Conclusions A HCD in Wistar rats promoted, in addition to higher body weight gain and increased serum LDL cholesterol levels, overexpression of β- and γ-catenin in the detrusor muscle cells. Similar finding was observed in the BOO group. Higher Cadherin-11 expression was observed only in the HCD-treated rats. These findings may be associated with bladder dysfunctions that occur under such situations.

Phenolic compounds from Rosemary (Rosmarinus officinalis L.) attenuate oxidative stress and reduce blood cholesterol concentrations in diet-induced hypercholesterolemic rats

Abstract Background Phenolic compounds combine antioxidant and hypocholesterolemic activities and, consequently, are expected to prevent or minimize cardiometabolic risk. Methods To evaluate the effect of an aqueous extract (AQ) and non-esterified phenolic fraction (NEPF) from rosemary on oxidative stress in diet-induced hypercholesterolemia, 48 male 4-week old Wistar rats were divided into 6 groups: 1 chow diet group (C) and 5 hypercholesterolemic diet groups, with 1 receiving water (HC), 2 receiving AQ at concentrations of 7 and 140 mg/kg body weight (AQ70 and AQ140, respectively), and 2 receiving NEPF at concentrations of 7 and 14 mg/kg body weight (NEPF7 and NEPF14, respectively) by gavage for 4 weeks. Results In vitro, both AQ and NEPF had remarkable antioxidant activity in the 2,2-diphenyl-1-picrylhydrazyl (DPPH●) assay, which was similar to BHT. In vivo, the group that received AQ at 70 mg/kg body weight had lower serum total cholesterol (−39.8%), non-HDL-c (−44.4%) and thiobarbituric acid reactive substance (TBARS) levels (−37.7%) compared with the HC group. NEPF (7 and 14 mg/kg) reduced the tissue TBARS levels and increased the activity of tissular antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase). Neither AQ nor NEPF was able to ameliorate the alterations in the hypercholesterolemic diet-induced fatty acid composition in the liver. Conclusions These data suggest that phenolic compounds from rosemary ameliorate the antioxidant defense in different tissues and attenuate oxidative stress in diet-induced hypercholesterolemic rats, whereas the serum lipid profile was improved only in rats that received the aqueous extract.

Effect Of Pitavastatin On Vascular Reactivity In Hypercholesterolemic Rabbits.

Pitavastatin is the newest statin available in Brazil and likely the one with fewer side effects. Thus, pitavastatin was evaluated in hypercholesterolemic rabbits in relation to its action on vascular reactivity. To assess the lowest dose of pitavastatin necessary to reduce plasma lipids, cholesterol and tissue lipid peroxidation, as well as endothelial function in hypercholesterolemic rabbits. Thirty rabbits divided into six groups (n = 5): G1 - standard chow diet; G2 - hypercholesterolemic diet for 30 days; G3 - hypercholesterolemic diet and after the 16th day, diet supplemented with pitavastatin (0.1 mg); G4 - hypercholesterolemic diet supplemented with pitavastatin (0.25 mg); G5 - hypercholesterolemic diet supplemented with pitavastatin (0.5 mg); G6 - hypercholesterolemic diet supplemented with pitavastatin (1.0 mg). After 30 days, total cholesterol, HDL, triglycerides, glucose, creatine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT) were measured and LDL was calculated. In-depth anesthesia was performed with sodium thiopental and aortic segments were removed to study endothelial function, cholesterol and tissue lipid peroxidation. The significance level for statistical tests was 5%. Total cholesterol and LDL were significantly elevated in relation to G1. HDL was significantly reduced in G4, G5 and G6 when compared to G2. Triglycerides, CK, AST, ALT, cholesterol and tissue lipid peroxidation showed no statistical difference between G2 and G3-G6. Significantly endothelial dysfunction reversion was observed in G5 and G6 when compared to G2. Pitavastatin starting at a 0.5 mg dose was effective in reverting endothelial dysfunction in hypercholesterolemic rabbits.

Effect of Pitavastatin on Vascular Reactivity in Hypercholesterolemic Rabbits

Background: Pitavastatin is the newest statin available in Brazil and likely the one with fewer side effects. Thus, pitavastatin was evaluated in hypercholesterolemic rabbits in relation to its action on vascular reactivity. Objective: To assess the lowest dose of pitavastatin necessary to reduce plasma lipids, cholesterol and tissue lipid peroxidation, as well as endothelial function in hypercholesterolemic rabbits. Methods: Thirty rabbits divided into six groups (n = 5): G1 - standard chow diet; G2 - hypercholesterolemic diet for 30 days; G3 - hypercholesterolemic diet and after the 16th day, diet supplemented with pitavastatin (0.1 mg); G4 - hypercholesterolemic diet supplemented with pitavastatin (0.25 mg); G5 - hypercholesterolemic diet supplemented with pitavastatin (0.5 mg); G6 - hypercholesterolemic diet supplemented with pitavastatin (1.0 mg). After 30 days, total cholesterol, HDL, triglycerides, glucose, creatine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT) were measured and LDL was calculated. In-depth anesthesia was performed with sodium thiopental and aortic segments were removed to study endothelial function, cholesterol and tissue lipid peroxidation. The significance level for statistical tests was 5%. Results: Total cholesterol and LDL were significantly elevated in relation to G1. HDL was significantly reduced in G4, G5 and G6 when compared to G2. Triglycerides, CK, AST, ALT, cholesterol and tissue lipid peroxidation showed no statistical difference between G2 and G3-G6. Significantly endothelial dysfunction reversion was observed in G5 and G6 when compared to G2. Conclusion: Pitavastatin starting at a 0.5 mg dose was effective in reverting endothelial dysfunction in hypercholesterolemic rabbits.

High plasma concentrations of asymmetric dimethylarginine inhibit ischemic cardioprotection in hypercholesterolemic rats

A low concentration of nitric oxide associated with a high concentration of asymmetric dimethylarginine (ADMA) can explain the lack of ischemic cardioprotection observed in the presence of hypercholesterolemia. The objective of the present study was to evaluate the effect of hypercholesterolemia on ischemic pre- and postconditioning and its correlation with plasma concentrations of ADMA. Male Wistar rats (6-8 weeks old) fed a 2% cholesterol diet (n = 21) for 8 weeks were compared to controls (n = 25) and were subjected to experimental myocardial infarction and reperfusion, with ischemic pre- and postconditioning. Total cholesterol and ADMA were measured in plasma before the experimental infarct and the infarct area was quantified. Weight, total cholesterol and plasma ADMA (means ± SE; 1.20 ± 0.06, 1.27 ± 0.08 and 1.20 ± 0.08 vs0.97 ± 0.04, 0.93 ± 0.05 and 0.97 ± 0.04 µM) were higher in animals on the hypercholesterolemic diet than in controls, respectively. Cardioprotection did not reduce infarct size in the hypercholesterolemic animals (pre: 13.55% and post: 8% compared to 7.95% observed in the group subjected only to ischemia and reperfusion), whereas infarct size was reduced in the animals on a normocholesterolemic diet (pre: 8.25% and post: 6.10% compared to 12.31%). Hypercholesterolemia elevated ADMA and eliminated the cardioprotective effects of ischemic pre- and postconditioning in rats.

Effects of a ferment soy product on the adipocyte area reduction and dyslipidemia control in hypercholesterolemic adult male rats

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Intake of isoflavone-supplemented soy yogurt fermented with Enterococcus faecium lowers serum total cholesterol and non-HDL cholesterol of hypercholesterolemic rats

The aim of this study was to obtain an isoflavone-supplemented soy yogurt, fermented with Enterococcus faecium CRL 183 and Lactobacillus helveticus ssp jugurti, with suitable sensory properties and to assess the effects of the final product on blood lipids in hypercholesterolemic rats. Four isoflavone supplementation procedures were tested, in which the isoflavone was added at these stages: (1) before heat-treatment; (2) after heating and before fermentation; (3) after fermentation and (4) in the okara (by-product of soy milk) flour stirred into the fermented product when consumed. The products were subjected to a test of sensory acceptability. To assess their potential hypocholesterolemic properties in vivo, four groups of rats were used: control (C), hypercholesterolemic (H), hypercholesterolemic plus fermented product (HF) and hypercholesterolemic plus isoflavone-supplemented fermented product (HFI). Hypercholesterolemia was induced in rats of groups H, HF and HFI by feeding them on a commercial rat chow to which cholesterol and cholic acid had been added. Total, HDL and non-HDL cholesterol and triglycerides were measured in the blood of the rats. No significant sensorial differences were detected among the samples of soy yogurt supplemented with isoflavones at various processing stages. Rats fed a fermented soy product enriched with isoflavones (HFI group) had significantly (P < 0.05) less serum total cholesterol (15.5%) compared with rats fed a hypercholesterolemic diet (H group). Non-HDL cholesterol was less (P < 0.05) in rats fed a fermented soy product enriched or not with isoflavones (27.4 and 23.2%) compared to H group. The HDL-C and triglyceride concentrations did not differ significantly among the groups. It was possible to obtain an isoflavone-supplemented soy yogurt with satisfactory sensory characteristics. The resulting supplemented soy yogurt was capable of producing a lipid-lowering effect in hypercholesterolemic rats, relative to the animals that did not consume this product.

Soybean glycinin improves HDL-C and suppresses the effects of rosuvastatin on hypercholesterolemic rats

Background: This study was an investigation of the effects of ingesting a daily dose of isolated glycinin soy protein (11S globulin), in association with rosuvastatin, on the control of hypercholesterolemia in experimental animals.Methods: Male Wistar rats were kept in individual cages under appropriate controlled conditions of temperature, light and humidity. The animals were divided into five groups (n = 9): 1) standard (STD): fed on casein as protein source; 2) hypercholesterolemic (HC): STD plus 1% cholesterol and 0.5% cholic acid; 3) HC+11S: hypercholesterolemic + glycinin (300 mg/kg/day); 4) HC+ROS: hypercholesterolemic + rosuvastatin (10 mg/kg/day); 5) HC+11S+ROS: HC diet, the 11S protein and the drug in the doses given in (3) and (4). The protein and the drug were administered by gavage for 28 days. The results indicated that the addition of 1% cholesterol and 0.5% cholic acid induced hypercholesterolemia in the animals without interfering with their weight gain.Results: A single daily dose of glycinin contributed an additional 2.8% of dietary protein intake and demonstrated its functional role, particularly in raising HDL-C, decreasing triglycerides in the liver and improving the atherogenic index in animals exposed to a hypercholesterolemic diet.Conclusion: Most of the beneficial effects of the isolated treatments disappeared when the drug (rosuvastatin) and the protein (glycinin) were taken simultaneously. The association was shown not to interact additively, as noted in the plasma levels of total cholesterol and non-HDL cholesterol, and in the significant increase of cholesterol in the liver. Studies are in progress to identify the effects of peptides derived from the 11S globulin and their role in cholesterol metabolism.

beta-Conglycinin (7S) and glycinin (11S) exert a hypocholesterolemic effect comparable to that of fenofibrate in rats fed a high-cholesterol diet

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Soybean glycinin (11S) increases HDL-cholesterol in hypercholesterolemic rats

Purpose: The purpose of this paper is to determine the effects of isolated soy glycinin (11S) on lipid metabolism in animals subjected to a hypercholesterolemic diet. Design/methodology/approach: Male Wistar rats were kept in individual cages under appropriate conditions. The animals were divided into three groups (n=9): normal diet (STD) given a diet containing casein as protein source, recommended in AIN-93M; hypercholesterolemic (HC) fed a normal diet with 1 per cent cholesterol and 0.5 per cent cholic acid; and hypercholesterolemic+glycinin (HC+11S), fed a hypercholesterolemic diet, plus 11S soy protein (300 mg/kg/day), dissolved in saline and administered by gavage. After 28 days, the animals were sacrificed and blood and liver removed for biochemical analysis of total cholesterol (TC), HDL-cholesterol (HDL-C) and triglycerides (TG) in the plasma, hepatic TC and TG. Findings: A single daily dose of glycinin given to the hypercholesterolemic group demonstrated its functional role, particularly in raising HDL-C and reducing triglycerides in the liver. Originality/value: This study demonstrates the action of the 11S globulin in soybean as a serum lipid lowering agent, in addition to its nutritional properties, especially in raising the HDL-C. © Emerald Group Publishing Limited.

Anti-Atherogenic Effects of a Phenol-Rich Fraction from Brazilian Red Wine (Vitis labrusca L.) in Hypercholesterolemic Low-Density Lipoprotein Receptor Knockout Mice

Moderate wine intake (i.e., 1-2 glasses of wine a day) is associated with a reduced risk of morbidity and mortality from cardiovascular disease. The aim of this study was to evaluate the anti-atherosclerotic effects of a nonalcoholic ethyl acetate fraction (EAF) from a South Brazilian red wine obtained from Vitis labrusca grapes. Experiments were carried out on low-density lipoprotein (LDL) receptor knockout (LDLr-/-) mice, which were subjected to a hypercholesterolemic diet and treated with doses of EAF (3, 10, and 30 mg/kg) for 12 weeks. At the end of the treatment, the level of plasma lipids, the vascular reactivity, and the atherosclerotic lesions were evaluated. Our results demonstrated that the treatment with EAF at 3 mg/kg significantly decreased total cholesterol, triglycerides, and LDL plus very low-density lipoprotein levels compared with control hypercholesterolemic mice. The treatment of mice with EAF at 3 mg/kg also preserved the vasodilatation induced by acetylcholine on isolated thoracic aorta from hypercholesterolemic LDLr-/- mice. This result is in agreement with the degree of lipid deposit on arteries. Taken together, the results show for the first time that the lowest concentration of an EAF obtained from a red wine produced in southern Brazil significantly reduced the progression of atherosclerosis in mice.

The effects of high-intensity resistance exercise on the blood lipid profile and liver function in hypercholesterolemic hamsters

It is well established that atherogenic dyslipidemia, characterized by high levels of triglycerides (TG), total cholesterol (TC), and low-density lipoprotein (LDL) cholesterol and low levels of high-density lipoprotein (HDL) cholesterol, constitutes important risk factors for cardiovascular disease. Regular exercise has been associated with a reduced risk for metabolic diseases. However, studies supporting the concept that resistance exercise is a modifier of blood lipid parameters are often contradictory. The aim of this study was to investigate the effects of high-intensity resistance exercise on the serum levels of TG, TC, HDL and non-HDL cholesterol, glucose, and the liver function enzymes alanine aminotransferase (ALT, EC 2.6.1.2) and aspartate aminotransferase (AST, EC 2.6.1.1) in golden Syrian hamsters (Mesocricetus auratus (Waterhouse, 1839)) fed a hypercholesterolemic diet. Sedentary groups (S) and exercise groups (E) were fed a standard diet (SS and ES) or a cholesterol-enriched diet (standard plus 1% cholesterol, SC and EC). Resistance exercise was performed by jumps in the water, carrying a load strapped to the chest, representing 10 maximum repetitions (10 RM, 30 s rest, five days per week for five weeks). Mean blood sample comparisons were made by ANOVA + Tukey or ANOVA + Kruskal-Wallis tests (p < 0.05) to compare parametric and nonparametric samples, respectively. There were no differences in blood lipids between the standard diet groups (SS and ES) (p > 0.05). However, the EC group increased the glucose, non-HDL, and TC levels in comparison with the ES group. Moreover, the EC group increased the TG levels versus the SC group (p < 0.05). In addition, the ALT levels were increased only by diet treatment. These findings indicated that high-intensity resistance exercise contributed to dyslipidemia in hamsters fed a hypercholesterolemic diet, whereas liver function enzymes did not differ in regards to the exercise protocol.

The Role of Black Rice (Oryza sativa L.) in the Control of Hypercholesterolemia in Rats

Cardiovascular disease is a serious public health problem; it is the first cause of death in Brazil and in developed countries. Thus, it is essential to search for alternative sources such as some functional foods to prevent and control the risks of this disease. The purpose of this study was to evaluate the lipidemic parameters in hypercholesterolemic rats fed diets containing black rice variety IAC 600 or unrefined rice. Adult male Wistar rats (Rattus norvegicus var. albinos) were used, weighing about 200-220 g. The animals were divided into four groups: the first received a control casein diet, the second received hypercholesterolemic diet, and the other two groups, after induction of hypercholesterolemia, received the test diets, the first containing 20% black rice and the second 20% unrefined, for 30 days. It was observed that diet containing black rice reduced the level of plasma cholesterol, triglycerides, and low-density lipoprotein. For high-density lipoprotein values, the diet that provided an increase in the levels was the black rice. The diet containing black rice was more effective in controlling the lipidemia in rats compared with the whole rice diet.