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Biomedical subjects

Z Madar

Publications and source records attributed to Z Madar.

At least 19 recordsLinked to original sources
PubMed2002

Hyperglycemia reduces nitric oxide synthase and glycogen synthase activity in endothelial cells.

Hyperglycemia is considered a primary cause of diabetic vascular complications. A hallmark of vascular disease is endothelial cell dysfunction characterized by diminished nitric-oxide (NO)-dependent phenomena such as vasodilation, angiogenesis, and vascular maintenance. This study was designed to investigate the effects of a high level of D-glucose on endothelial NO response, oxidative stress, and glucose metabolism. Bovine aortic endothelial cells (BAECs) were pretreated with a high concentration of glucose (HG) (22 mmol/L) for at least 2 weeks and compared with control cells exposed to 5 mmol/L glucose (NG). The effect of chronic hyperglycemia on endothelial NO-synthase (eNOS) activity and expression, glycogen synthase (GS) activity, extracellular-signal-regulated kinase (ERK 1,2), p38, Akt expression, and Cu/Zn superoxide-dismutse (SOD-1) activity and expression were determined. Western blot analysis showed that eNOS protein expression decreased in HG cells and was accompanied by diminished eNOS activity. The activity of GS was also significantly lower in the HG cells than in NG cells, 25.0+/-17.4 and 89+/-22.5 nmol UDP-glucose.mg protein(-1)x min(-1), respectively. Western blot analysis revealed a 40-60% decrease in ERK 1,2 and p38 protein levels, small modification of phosphorylated Akt expression, and a 30% increase in SOD-1 protein expression in HG cells. Although SOD expression was increased, no change was observed in SOD activity. These results support the findings that vascular dysfunction due to exposure to pathologically high D-glucose concentrations may be caused by impairment of the NO pathway and increased oxidative stress accompanied by altered glucose metabolism.

Animals↗
PubMed2001

Diet and diabetic state modify glycogen synthase activity and expression in rat hepatocytes.

Glycogen synthase (GS), a key regulatory enzyme in glycogen synthesis, is controlled by multisite phosphorylation and allosteric regulation and is activated by insulin. This study investigated changes in GS activity and expression in hepatocytes isolated from rats under altered nutritional and diabetic conditions. Experiments were carried out in healthy rats fed a chow diet, rats on high simple sugar (60% of energy from fructose and sucrose) or high fat (46% of energy from fat) diet, and in rats with streptozotocin induced diabetes. In the presence of insulin, activated GS activity (GS(I) form) was increased by 89% in hepatocytes isolated from healthy rats. The stimulatory effect of insulin on GS activity and expression was blunted by cycloheximide and actinomycin treatment. In rats fed a high simple sugar or high fat diet, insulin stimulation of GS(I) in isolated hepatocytes was impaired and GS expression was significantly lower in rats fed the high fat diet in comparison to controls. GLUT-2 protein expression was significantly lowered by both the high fat and high simple sugar diets. In hepatocytes isolated from diabetic rats, total GS activity (GS(T)) was lower than in hepatocytes from healthy animals. Insulin added to the incubation medium did not stimulate GS activity, demonstrating impaired sensitivity to insulin in diabetic rats. However, insulin administration significantly increased GS expression indicating that a defect in synthase phosphorylation may be responsible for impaired GS activity in the diabetic state. The results presented in this study further confirm that GS activity is affected by both dietary and hormonal factors which can be measured in a rat hepatocyte model.

Journal Article↗
PubMed2000

Dietary regulation and localization of apoptosis cascade proteins in the colonic crypt.

This study was designed primarily to assess the localization of apoptosis cascade proteins along the rat colonic crypt and secondarily to test whether the activity and/or localization of these proteins are affected by the enrichment of the diet with the soluble fiber pectin. Expression of apoptosis cascade proteins was assessed in isolated colonocytes harvested from the luminal and basal crypt colonocyte populations. Two different dietary regimens were tested: a standard diet (diet A), and a diet enriched in pectin (diet B), a soluble fiber that undergoes fermentation in the cecum and produces high concentrations of intracolonic short-chain fatty acids. Caspase-1 expression was maximal in luminal colonocytes of rats fed diet B, as evidenced by Western blot and immunohistological analyses. Expression of the cleaved poly(ADP-ribose) polymerase product was elevated in both the luminal and basal colonocytes of the pectin-fed group, whereas in rats fed diet A, the expression was lower, especially in basal crypt colonocytes. The highest expression of the antiapoptotic protein Bcl-2 was observed in the lower compartments of the colonic crypt tissue and was maximal in the rat group fed a standard diet. The apoptotic index in colonocytes of rats fed diet B was higher than that measured in rats fed diet A. Cumulatively, our results indicate that apoptosis cascade proteins are differentially localized along the lumen-crypt axis, and their expression and activity may be controlled by dietary components. These results may, at least partially, account for the documented protective effect of butyrogenic fibers on colorectal cancer.

Animals↗
PubMed2000

Adaptation of Sprague Dawley rats to long-term feeding of high fat or high fructose diets.

BACKGROUND: Present animal models used to emulate type 2 diabetes may not accurately reflect the metabolic changes that occur in humans. AIM OF THE STUDY: The purpose of this research was to evaluate diets reported to induce insulin resistance and impaired glucose metabolism in rats as a potentially useful model for studying type 2 diabetes. METHODS: Three groups of male Sprague Dawley rats (n=7) were fed either a control diet, based on AIN recommendations (53% cornstarch, 10% sucrose and 7% soybean oil), a high fat diet (25% soybean oil, 35% cornstarch) or a high fructose diet (53% fructose, 10% sucrose) for a 3 month period. Glucose tolerance tests were carried out in week 3 and week 9 of the experiment. At the termination of the experiment, serum insulin, glucose, cholesterol and triacylglycerols were measured. Glucose incorporation into glycogen and glycogen synthase activity were measured in soleus muscles. RESULTS: Similar weight gain was observed for all three groups of rats. Glucose tolerance curves and fasting glucose levels were not significantly different at any time point in the experiment. Insulin levels were unchanged for the controls (171+/-21 pM), high fructose (164+/-16 pM) and high fat (181+/-30 pM) diets. Fasting serum triacylglycerols and cholesterol levels were not significantly elevated by dietary treatment. In soleus muscles, rats on all three diets had a significant increase in glycogen synthesis in response to insulin, but synthesis was similar in all three groups. Glycogen synthase activity was also not significantly affected by long-term dietary intervention. CONCLUSIONS: In this study, healthy Sprague Dawley rats fed high fat or high fructose diets for 3 months adapted to the nutritional intervention without developing classical signs of insulin resistance and impaired glucose tolerance.

Adaptation, Biological↗
PubMed2000

Apoptosis cascade proteins are regulated in vivo by high intracolonic butyrate concentration: correlation with colon cancer inhibition.

The present study was aimed at evaluating the effect of high intracolonic butyrate concentrations, either through fermentation of a soluble fiber-enriched diet or via intracolonic butyrate instillation, on colon cancer in a chemically induced (dimethylhydrazine) rat model. The effects were tested in four groups of dimethylhydrazine-treated rats: (i) rats fed a standard diet, (ii) rats fed a diet enriched with 15% citrus pectin, a soluble fiber that ferments and produces a high concentration of intracolonic butyrate, (iii) rats fed a standard diet and intrarectally instilled with a sodium butyrate solution (50 mM), (iv) rats fed a standard diet and intrarectally instilled with sodium butyrate vehicle solution (100 mM NaCl). The apoptotic index in the distal colon of rats fed pectin was higher than in colonic tissue from rats fed a standard diet. The expression of caspase-1, a cysteine protease implicated in the regulation of programmed cell death, as detected by both Northern and Western analysis, showed the highest mRNA and protein levels in colonic tissue from rats intrarectally instilled with butyrate. Immunohistology confirmed the Western blot findings. Expression of the cleaved poly(ADP-ribose) polymerase product, a downstream nuclear substrate for caspase-3 in the apoptotic pathway, was elevated in both the pectin-fed and butyrate-instilled groups. Expression of the antiapoptotic protein Bcl-2 was significantly reduced following pectin feeding as well as butyrate instillation. The highest expression of Bcl-2 was observed in tumor tissue. A marked reduction in aberrant crypt number was observed in colonic tissue obtained from both the pectin-fed and butyrate-instilled groups relative to rats from the standard diet group. The average tumor volume per rat in both the pectin-fed and butyrate-instilled groups was significantly lower than in rats from the standard diet and the sodium butyrate vehicle-instilled groups. We conclude that high butyrate levels, either instilled or obtained following fermentation of soluble dietary fibers, inhibit early and late events in colon tumorigenesis by controlling the transcription expression and activity of key proteins involved in the apoptotic cascade.

1,2-Dimethylhydrazine↗
PubMed2000

Transplacental effects of maternal feeding with high fat diets on lipid exchange and response of the splenic lymphoid system in mice offspring exposed to low doses of carcinogen.

We studied whether feeding pregnant female mice with different fats affects lipid exchange and activity of the splenic lymphoid system in offspring exposed to low doses of carcinogen. Female mice were fed diets with either 7% or 15% corn oil or olive oil. The 4-week-old offspring of these mice were transferred to a chow diet, and exposed to a low dose of the carcinogen, dimethylbenz(a)antracene (2 mg/kg). Results of experiments were studied 5 months later. Concentrations of polyunsaturated linoleic and oleic acids were determined in the blood and liver of mothers and offspring. The activity of the splenic immune system in offspring was studied using immunohistochemical methods for evaluating the number of different types of lymphocytes (B and T cells), mitotic and apoptotic indexes and the number of Fas-positive lymphocytes. Serum concentrations of the fatty acids examined were unchanged in the blood of the mothers and their offspring. Concentration of both linoleic and oleic acids was significantly higher in the liver of mothers fed the 15% olive-oil or corn-oil diets. This high level was maintained in linoleic acid in offspring of mothers fed the 15% olive-oil diet. Spleen weight was higher in offspring of mothers fed a 15% corn-oil diet compared to those fed the 7% corn-oil diet. The 15% olive-oil diet slightly decreased the weight of the spleen compared to counterparts fed the 15% corn-oil diet. Immunohistochemical studies showed that the olive diet, partially of 15%, significantly stimulated B-cell blast transformation. The finding reflects the reaction of B lymphocyte-producing splenic zones to the carcinogenic effect, though to a weak extent. T lymphocyte-producing zones did not respond to the diets studied, probably due to the weak carcinogenic effect and lack of tumor appearance. The Fas activity of both B and T cells in the spleen was stimulated by the carcinogen and enhanced by feeding the mothers on the olive-oil diet. Maternal feeding with a diet rich in olive oil before pregnancy results in stimulation of morphological and functional attributes of the splenic immune system of the offspring, particularly related to producing of B lymphocytes.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2000

Pectin-enriched diet affects distribution and expression of apoptosis-cascade proteins in colonic crypts of dimethylhydrazine-treated rats.

The colonic crypt contains highly proliferative cells in its base and differentiated cells on its luminal surface. Carcinogenesis significantly affects this orderly cellular distribution. The aims of this study were: i) to examine the expression of apoptosis-related proteins along the crypt-lumen axis during 1, 2-dimethylhydrazine (DMH)-induced carcinogenesis, ii) to assess whether a diet supplemented with the soluble fiber pectin affects those parameters, in comparison to non-carcinogen-treated rats and in relation to rats fed a standard diet and treated with DMH. The pectin-enriched diet induced upregulation of active caspase-1 subunit (20 kDa) and of caspase-3 precursor in DMH-treated rats. Pectin enhanced caspase-3 activity in all colonocyte populations, in both non-DMH and DMH-treated rats. The luminal colonocytes exhibited higher caspase-3 activity than proliferative colonocytes of rats fed a standard diet in non-DMH and DMH-treated rats, whereas in pectin-fed non-DMH-treated rats, equal activity was measured among all colonocyte populations. In the DMH-treated rats, the cleaved poly(ADP-ribose) polymerase subunit (89 kDa) was detected in luminal colonocytes of rats fed pectin and was higher than in rats fed the standard diet. Bak was equally expressed in isolated colonocytes from rats of both dietary groups treated with DMH and in the normal rats fed pectin, whereas in the non-DMH-treated rats fed a standard diet, higher expression was obtained in differentiated colonocytes. In the DMH-treated rats, Bcl-2 expression was lower in all colonocytes harvested from rats fed pectin, relative to rats fed the standard diet. Apoptotic index in the DMH-treated groups was higher in rats receiving the pectin diet compared with the standard diet in both the differentiated cell populations and the proliferating colonocytes. Average tumor number and volume per rat were lower in rats fed pectin. These findings indicate that dietary fibers regulate expression, function and distribution of apoptotic-related proteins in the crypt during colon carcinogenesis, changes that probably induce a reduction in tumor volume. We assume that butyrate, produced following fermentation of pectin, may play a key role in these effects.

1,2-Dimethylhydrazine↗
PubMed2000

Soluble polysaccharide and biomass of red microalga Porphyridium sp. alter intestinal morphology and reduce serum cholesterol in rats.

The present study investigated the effects of the red microalga Porphyridium sp. on gastrointestinal physiology and lipid metabolism in male Sprague-Dawley rats. Diets containing dietary fibre from pelleted red microalgal cells (biomass) or their sulfated polysaccharide, pectin or cellulose (control) were fed to rats for a period of 30 d. All three fibre-supplemented diets increased the length of both the small intestine and colon, with a significantly greater effect in rats fed the algal polysaccharide. The polysaccharide also increased mucosa and muscularis cross-sectional area of the jejunum, and caused hypertrophy in the muscularis layer. The algal biomass significantly lowered gastrointestinal transit time by 44% in comparison with the control rats. Serum and mucosal cholecystokinin levels were lower in rats on the pectin and polysaccharide diets, while cholecystokinin levels in rats fed algal biomass were not different from those in the control animals. In comparison with the control diet, all the experimental diets significantly lowered serum cholesterol levels (22-29%). Feeding of non-fermentable algal polysaccharide or biomass significantly increased faecal weight and bile acid excretion compared with pectin-fed or control rats. The algal polysaccharide and biomass were thus shown to be potent hypocholesterolaemic agents active at low concentrations in the diet. Both metabolic and morphological changes were observed following consumption of algae, suggesting several possible mechanisms by which the alga affects lipid metabolism. The results presented in the present study encourage the use of red microalga as a functional food.

Analysis of Variance↗
PubMed1999

Cholesterol and triglyceride reduction in rats fed Matthiola incana seed oil rich in (n-3) fatty acids.

Seeds of Matthiola incana contain oil rich (55-65%) in (n-3) linolenic acid. Selected lines were developed and evaluated for their agronomic and chemical parameters. Extracted oil was fed for 6 weeks to rats, which were compared with rats fed a diet containing coconut oil or sunflower oil. Cholesterol levels were significantly lowest in rats fed diets rich in M. incana oil (27% reduction), and triglycerides were significantly lower in rats receiving either M. incana or sunflower oil (36% reduction). The contents of arachidonic acid and other (n-6) fatty acids were significantly the lowest in the liver and plasma of rats that had received M. incana oil. The levels of (n-3) fatty acids were significantly greater in both the liver and plasma of rats fed M. incana oil. The ratio of (n-3)/(n-6) long-chain fatty acids in the plasma was 7 times higher in rats fed with M. incana oil than in those fed with sunflower oil and 6 times higher than in those fed coconut oil. The results demonstrate for the first time a beneficial effect of dietary M. incana oil in reducing cholesterol levels and increasing (n-3) fatty acid levels in the plasma. This new, terrestrial plant source of (n-3) fatty acids could replace marine oils and thereby contribute beneficially to the human diet.

Animals↗
PubMed1999

Cataract development in sand and galactosemic rats fed a natural tomato extract.

This study investigated the effect of a natural tomato extract (TE) on cataract formation in two animal models. A TE containing 5% lycopene was included in the diet of diabetic sand rats at 0.2%, and Sprague Dawley rats were fed a high-galactose diet (30 g/100 g of diet), supplemented with either the lycopene-rich extract at concentrations of 0.2, 0.4, and 0.8% or BHT (0.2%). TE had no significant effect on plasma glucose levels or cataract development in sand rats; however, in rats maintained on a diet rich in galactose, both BHT and TE decreased cataract incidence, and grades were lower than in control animals. In addition, lens protein and reduced glutathione levels were higher and aldose reductase activity was lower than in the control group. The results suggest that antioxidants act as protective agents when oxidative stress is a primary cause of cataract formation but may be less effective in preventing cataracts in hyperglycemic animals.

Analysis of Variance↗
PubMed1997

Acarbose reduces blood pressure in sucrose-induced hypertension in rats.

Hypertension is often associated with impaired glucose tolerance and high insulin levels, factors that contribute to insulin resistance. The present study evaluates the effect of acarbose, a hypoglycemic drug that inhibits carbohydrate digestion in sucrose-induced hypertension in rats. The effects of diets fed to 3 groups of rats for a 16-week period were studied: sucrose + NaCl (1% wet volume [w/v]) with acarbose (0.04% wet weight [w/w]), sucrose + NaCl (1% w/v) without acarbose, and a third diet of complex carbohydrates. There was no statistical difference in the body weight between rats fed with or without acarbose. Fasting glucose levels were significantly lowered when treated with acarbose. Postprandial blood glucose and insulin levels were attenuated in rats fed sucrose + acarbose. Systolic blood pressure increased significantly (p < 0.001) in rats fed sucrose + NaCl for 3 months, whereas systolic blood pressure of acarbose-fed rats remained at the initial level. Blood pressure changes in the complex carbohydrate-fed group were lower than in rats fed sucrose. The urinary volume, Na+, and K+ of rats fed acarbose tended to increase compared to the acarbose-free diet (p < 0.05). We conclude that high insulin levels, impaired glucose tolerance and Na+ retention may contribute to the development of sucrose-induced hypertension. Acarbose prevents sucrose-induced increases in plasma glucose and insulin levels. Increases in urinary Na + may contribute indirectly to this effect with resultant normal systolic blood pressures.

Acarbose↗
PubMed1995

Changes in intestinal tunica muscularis following dietary fiber feeding in rats. A morphometric study using image analysis.

The morphological changes in the intestinal tunica muscularis induced by prolonged dietary fiber intake were determined in rat small intestine and colon with the aid of computerized image analysis. Thirty male Sprague-Dawley rats were fed either a fiber free, 15% cellulose or 15% pectin diet for 8 weeks. Intestine length was measured and stained cross sections of the jejunum, ileum, and colon were quantitated using image analysis. In the distal colon, muscle cell size was also determined. Despite lower weight gain in the pectin fed rats, both the small intestine and colon length were significantly increased. Cellulose feeding had a lesser effect on intestine length. Pectin fed rats had significantly increased relative tunica muscularis area (37.2 +/- 2.2 mm2) in ileum cross sections when compared to control (24.3 +/- 1.8 mm2) and cellulose fed rats (26.1 +/- 1.1 mm2). In the mid-colon, the tunica muscularis area was found to be pectin > cellulose > control (33.5 +/- 2.2; 29.7 +/- 1.7; 25.8 +/- 1.5 respectively) with significant differences reached between pectin and control rats. In jejunal samples, no differences were observed among the groups. Circular smooth muscle cell size in the distal colon was significantly increased following cellulose feeding but was less pronounced in the case of pectin. We conclude that fiber supplementation leads to morphological changes in the rat intestine including changes in length and tunica muscularis volume.

Animals↗
PubMed1995

Assessment of the nucleolar organizer regions by automated image analysis in benign and malignant colonic tumours and adjacent tissues in rats.

An automated computer image analysis technique was used to study the morphological parameters of argyrophilic nucleolar organizer regions (AgNORs) in chemically induced rat colonic tumours of different grades. Different nuclear parameters were of different diagnostic value. For distinguishing tumorous tissue from normal tissue all the parameters studied were capable of serving as diagnostic markers. Malignant processes could, however, be more reliably detected by means of the area of the nucleus, nuclear shape factor, area of AgNOR and ratio of AgNOR area to nuclear area. In macroscopically normal tissue adjacent to a tumour, the values of all the AgNOR parameters studied were similar to those in tumorous tissues. It can be concluded that the initial stages in tumorigenesis are accompanied by changes in all of the nucleus and AgNOR parameters, but as malignancy develops, only some of these parameters continue to change. Close correlations between nuclear parameters in malignant tissue suggest that for diagnostic purposes only nuclear and AgNOR areas should be used.

Adenocarcinoma↗
PubMed1995

Aldose reductase (EC 1.1.1.21) activity and reduced-glutathione content in lenses of diabetic sand rats (Psammomys obesus) fed with acarbose.

The effects of acarbose on cataract development, lens aldose reductase (EC 1.1.1.21) activity and lenticular reduced-glutathione content in diabetic sand rats (Psammomys obesus) were determined. Diabetic sand rats (diet-induced) were fed on diets with or without acarbose (0.4 g/kg) for 39 d. Daily plasma glucose, cataract incidence, aldose reductase and glutathione content were evaluated. After 19 d on acarbose, daily plasma glucose profile was significantly reduced compared with that of sand rats not receiving acarbose. Cataract incidence was markedly lower in sand rats treated with acarbose. After 20 d, cataracts had developed in 90% of the animals fed without acarbose, whereas none was observed in sand rats fed with acarbose. After 37 d acarbose treatment the incidence of cataracts reached only 30%. Compared with untreated animals, lens aldose reductase activity was significantly lower in sand rats fed with acarbose for 39 d (7.6 (SE 0.78) v. 3.5 (SE 0.55) mumol NADPH/mg protein per min respectively, P < 0.001). Concomitantly, significantly higher lenticular protein and reduced-glutathione contents (90 (SE 23) v. 240 (SE 23.5) micrograms/mg tissue respectively, P < 0.001 and 369 (SE 48.6) v. 645 (SE 71.1) micrograms/mg tissue respectively, P < 0.001) were found. These results suggest that decreasing hyperglycaemia, accompanied by lower aldose reductase activity obtained by acarbose, led to a significant preventive effect on cataract development in sand rats.

Acarbose↗
PubMed1995

Enrichment of an Israeli ethnic food with fibres and their effects on the glycaemic and insulinaemic responses in subjects with non-insulin-dependent diabetes mellitus.

The effects of various sources of dietary fibre on the high glycaemic index of an Israeli ethnic food, melawach, were investigated in subjects with non-insulin-dependent diabetes mellitus (NIDDM). Locust-bean (Ceratonia siliqua) gum significantly decreased the glucose response to, and glycaemic index of, melawach in these diabetic subjects (P < 0.05). It also tended to decrease their insulinaemic response and insulinaemic index, but differences were not significant. Dietary fibre from lupin (Lupinus albus) and insoluble maize-cob fibre did not affect glucose and insulin levels in NIDDM volunteers. Subjects with a BMI < 30 kg/m2 exhibited similar glucose, but not insulin, responses to fibre. Locust-bean gum had no significant effect on glycaemic response in NIDDM subjects with a BMI > 30 kg/m2, whereas insulinaemic response decreased. The results indicate that foods containing the same nutrients in almost the same amounts, but differing in added dietary fibre, lead to different physiological responses in diabetic subjects. Furthermore, insulin response should be considered when fibre is incorporated into the diabetic's diet.

Adult↗
PubMed1995

Starvation and refeeding regulate glycogen synthase gene expression in rat liver at the posttranscriptional level.

Starvation and refeeding affect glycogen metabolism. The effects of starvation and refeeding on the level of glycogen synthase (GS) gene expression were examined in rat liver. Depletion of hepatic glycogen stores by 72 h of starvation (7% of control) was supercompensated by 24 h of refeeding a standard laboratory diet (247% of control). Upon further refeeding, glycogen concentration gradually returned to control levels after 120 h. After 72 h of starvation, GS activity and immunoreactive protein in the liver were 60-64% lower than in control rats with free access to food. After 72 h of refeeding, GS activity and immunoreactive protein returned to control values. No significant differences in GS mRNA levels were found between fed, starved and refed rats, as determined by Northern blot analysis and PCR quantification, indicating that the long-term regulation of GS gene expression in starvation and refeeding occurs via a posttranscriptional mechanism. The amount of GS mRNA associated with polyribosomes was 90% lower in starved than in fed rats. These data indicate that the efficiency of GS mRNA translation, rather than its abundance, decreases during starvation.

Animals↗