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Z Madar

Publications and source records attributed to Z Madar.

83 records · Page 5Linked to original sources

Metabolic and morphometric changes in small and large intestine in rats fed high-fiber diets.

Structural modifications of the intestine following fiber intake may play an important role in the physiological effects induced by dietary fiber. The aim of this study was to examine possible mechanisms for the hypocholesterolemic effects of dietary fibers by evaluating both biochemical and morphometric parameters. Thirty male Sprague-Dawley rats were divided into 3 groups and fed either a fiber-free, 15% fiber high methoxy pectin, or 15% cellulose diet for a 4-wk period. Plasma cholesterol levels, hepatic enzyme activity, and fecal bile acid excretion were determined, and changes in the intestinal structure were evaluated. Daily fecal bile acid excretion was significantly higher in rats fed the pectin diet accompanied by elevated HMG-CoA reductase activity. Pectin feeding led to significant elongation of both the small and large intestine whereas cellulose only affected colon length. Computerized image analysis of intestinal cross-sections showed enlarged muscle area in the ileum and midcolon of pectin-fed rats and greater mucosal area in the colon. Circular muscle cell hypertrophy was also observed in the colon length. Computerized image analysis of intestinal cross-sections showed enlarged muscle area in the ileum and midcolon of pectin-fed rats and greater mucosal area in the colon. Circular muscle cell hypertrophy was also observed in the colon. In contrast, the effects of cellulose feeding were limited to elongation of the colon accompanied by muscle cell hypertrophy, and little effect on ileal morphology was documented. These data indicate that the hypocholestrolemic effects of pectin may be due to increased bile acid secretion accompanied by significant morphological changes in the ileum and colon.

Animals↗

Effect of miglitol and acarbose on starch digestion, daily plasma glucose profiles and cataract formation.

The effect of two alpha - glucosidase inhibitors, acarbose and miglitol, on postprandial glucose levels following wheat and potato starch loading was evaluated in sand rats with resultant dramatically reduced postprandial glucose levels. The inhibitory effect on starch digestion was dose concentration-dependent. Eighty-six and 72% inhibition was reached with 1 mg of miglitol and acarbose, respectively. Daily plasma glucose profiles and cataract formation were determined following long-term feeding with a diet containing acarbose and miglitol. Both drugs led to a significant reduction in glucose levels, acarbose being more potent, possibly via inhibition and delay of carbohydrate digestion. Acarbose caused a marked decrease in cataract incidence; the mechanism for this effect requires more elucidation. Since acarbose delayed and possibly prevented cataract formation in sand rats, we support the concept of its use as an adjuvant in the treatment of diabetic patients.

1-Deoxynojirimycin↗

The immune response of rat spleen to dietary fibers and to low doses of carcinogen: morphometric and immunohistochemical studies.

The effects of high-fiber diets on anticancer immune response are often masked by the effects of high-dose carcinogens. Using low levels of carcinogen the splenic immune response can be evaluated. Colon tumors were induced in rats with low doses of 1, 2-dimethylhydrazine, in the following experimental groups: rats fed with low fiber diet without exposure to carcinogen; rats exposed to the carcinogen and fed with low-fiber diet; rats exposed to carcinogen, and maintained on high-fiber diets, and did not develop tumors; and rats that developed tumors after exposure to carcinogen and maintenance on either low-fiber or high-fiber diets. After 24 weeks their spleens were studied immunohistochemically and morphometrically. In tumor-free rats, low doses of carcinogen caused significant response of the lymphoid system. This was manifested in the intensive blast transformation and in an increase in the number of dendritic cells and macrophages in different structures of the spleen. Dietary fibers activated these processes: the number of Ki-67 positive cells, macrophages and plasma cells increased significantly in the red pulp. A positive correlation was found between the effects of the carcinogen and proliferation of lymphocytes in the white pulp, and to lesser degree between high-fiber diets and lymphocytic abundance in the red pulp. The number of splenic apoptotic lymphocytes decreased in rats exposed to carcinogen. In tumor-bearing rats, immune insufficiency of the splenic responses was seen in the significant decrease of the areas of the mantle layer and the periarterial sheaths, as result of the decreased number of lymphocytes. Dietary fibers reduced the degree of this insufficiency. Even low doses of carcinogen cause a significant splenic immune response. This reaction has a compensatory character with macrophages, B and T cells participating. Addition of any high-fiber diet after the exposure to carcinogen activated the lymphocyte proliferation in the spleen.

1,2-Dimethylhydrazine↗

Transplacental effects of a 15% olive-oil diet on chemically-induced tumorigenesis in offspring.

We evaluated whether feeding pregnant female rats a diet high in olive-oil, that showed a tumor-preventive effect in adults, has a similar preventive effect on chemically-induced cancer in offspring (i.e. mammary glands and colon cancer in rats). The control group was fed the same 7% corn-oil diet as their mothers. Experimental group I was fed a 7% corn-oil diet while their mothers received a 15% olive-oil diet. Experimental group II was fed the same 15% olive-oil diet as their mothers. Female offspring were twice administered 7,12-dimethylbenz(a)antracene (DMBA) in doses of 10 mg/rat. Male offspring were injected 6 times with 1, 2-dimethylhydrazine (DMH) in doses of 20 mg/kg body weight. Effect of DMBA was manifested in a high rate of tumorigenesis: the number of tumor-bearing rats in control offspring reached 52.0%. This effect increased to 60.6% among offspring of experimental group II and to 67.7% in offspring of experimental group I. The mean tumor size increased significantly in control offspring. Following administration of DMH number of tumor-bearing rats was similar in all groups of offspring: 36.7%, 40.7% and 42.8%. Tumor types differed: the majority of tumors in the control group were benign polyps and adenomas (72.1%) and the number of adenocarcinomas was low (27.9%). The number of malignant tumors increased to 37.5% in offspring of experimental group II and to 45.5% in offspring of experimental group I. In control group offspring, a distinct tendency to increased body weight and a significant increase in spleen weight were seen. The findings indicate that feeding mothers a diet high in fat concentrations, even those with known tumor preventive significance in adults, lose this cancer-inhibiting role in offspring.

1,2-Dimethylhydrazine↗

Comparative effects of dimethylbenz(a)anthacene and a 15% olive-oil diet on cellular components and expression of apoptosis-related proteins in the spleen and mammary gland tumors of rats.

We compared effects of a high fat diet and a carcinogen on cellular elements of the spleen and mammary gland tumors in rats. Animals were fed a 15% olive-oil diet and a group of them were exposed to a carcinogen, dimethylbenz(a)anthacene (DMBA), in two doses of 10 mg/rat. Results of the experiments were evaluated after 4 months. We studied changes in the areas of different zones of the spleen related to production of B and T lymphocytes and also the number of cells in the spleen and tumors with positive reaction to receptors related to manifestation of apoptosis (FasL and p53) and receptors related to inhibition of apoptosis (bcl-2). In the spleen, dietary fats as well as DMBA alone decreased the zones related to production of B lymphocytes and increased the number of T lymphocytes. The combined effect of a carcinogen and a high fat diet manifested in an increase in the number of lymphoid cells and macrophages. In tumors from rats fed a low-fat diet, an extremely high number of lymphoid cells was seen in the border of tumors with T cell killers as a main component of these infiltrates. In tumors from rats fed a 15% olive-oil diet, the main component of the infiltrates were macrophages. High levels of p53+ and bcl-2+ cells were found in the spleen of rats exposed to a carcinogen. The combined effect of a carcinogen and the 15% olive-oil diet inhibited production of FasL and p53 receptors and stimulated synthesis of bcl-2 protein. In tumors, a carcinogen alone stimulated the high expression of FasL and p53 proteins, but in combination with the 15% olive-oil diet synthesis of these receptors decreased while production of bcl-2 protein increased sharply. This observation may serve as an additional proof of tumor-promoter effects of a high fat diet.

9,10-Dimethyl-1,2-benzanthracene↗

Transplacental effect of a 15% olive-oil diet on functional activity of immune components in the spleen and colon tumors of rat offspring.

We studied whether feeding pregnant female rats a 15% olive-oil diet affects the activity of lymph cells in the spleen and tumors in offspring with chemically-induced colon tumors. Rat mothers were fed either a 7% corn-oil or a 15% olive-oil diet. Five-week-old male offspring were divided into 3 groups. A control group was fed the 7% corn-oil diet similar to their mothers. The experimental group I was fed the 7% corn-oil diet whereas their mothers were fed the 15% olive-oil diet. The experimental group II was fed the same 15% olive-oil diet as their mothers. Experimental rats were injected weekly for 8 weeks with the carcinogen, 1,2-dimethylhydrazine (DMH), 20 mg/kg b.w. Results of experiments were studied 6 months later. The area of zones in the spleen responsible for producing B and T lymphocytes were measured and the number of cells counted. The activity of lymphoid elements of the spleen and of tumors were studied using immunohistochemical methods for evaluating the synthesis of CD8(+) lymphocytes and proliferative activity of lymphocytes in spleens and tumors. Feeding pregnant or lactating mothers with the 15% olive-oil diet had no marked tumor-protective effect on chemically-induced colon cancer in offspring. Diet-dependent changes were found at the cellular level. In the spleen of control offspring, the presence of a tumor was accompanied by an increase in the number of Ki-67(+) cells and CD8(+) lymphocytes in the red pulp. In experimental group I, DMH significantly increased the total cell number and the number of CD8(+) lymphocytes in the red pulp of the spleen in both tumor-bearing and tumor-free rats. In experimental group II, the total number of lymph cells and the number of CD8(+) lymphocytes increased compared to offspring fed a control diet. Tumor formation activated the proliferative activity of lymph elements. The total number of cells in infiltrates of the colon mucosa decreased in tumor-bearing rats compared to tumor-free counterparts, and this was seen in all three dietary groups of rats. In tumors from offspring of experimental group II, only the number of CD8(+) lymphocytes increased compared to those in offspring of experimental group I. The findings indicate that feeding mothers the 15% olive-oil diet had a cancer-inhibiting role in offspring, predominantly changes at the cellular level.

1,2-Dimethylhydrazine↗

Effects of a 15% orange-pulp diet on tumorigenesis and immune response in rats with colon tumors.

This study evaluated whether the feeding of rats with a 15% orange-pulp diet affects the lymphatic system and the tumorigenic response in rats exposed to a high dose of carcinogen. Five-week-old Sprague Dawley rats were divided into 2 groups fed a control chow diet or the same diet with 15% orange pulp. All rats were injected with 1,2-dimethylhydrazine (DMH) (20 mg/kg) weekly for 6 weeks. At 8 months, tumors, spleens and descending colon were taken from each group for analyses. Feeding rats the 15% orange-pulp diet did not reduce the tumor number but modified the number of adenocarcinomas found in the orange-pulp group compared to controls: 66.7% vs. 93.7%. The number of endophytic tumors was also significantly lower in the experimental group: 6.3% vs. 32.3% in controls. DMH affected the size of the splenic structures. The size of follicles and germinal centers decreased significantly in tumor-bearing rats compared to tumor-free rats. This effect was changed in rats fed the orange-pulp diet. In tumor-bearing rats from this group, only the area of the marginal zone decreased and the red pulp increased compared to tumor-free rats. The size of germinal centers significantly increased compared to tumor-bearing rats in controls. The total number of lymphoid cells decreased in germinal centers of spleens obtained from control tumor-bearing rats compared to tumor-free rats. DMH alone significantly increased the total number of cells in the colon mucosa of the rats fed the control diet. In tumor-bearing rats exposed to the carcinogen and fed the 15% orange-pulp diet, the total number of cells and the number of Ki-67+ cells increased in the depth of tumors whereas the number of CD8+ T cells increased in the colon mucosa, at the border of tumors and its depth. The caspase-3 protein a cysteine protease was elevated in tumors from rats fed the orange-pulp diet. Although the 15% orange-pulp diet did not change the number of tumors in the tumor-bearing rats, feeding rats orange pulp significantly decreased the number of endophytic tumors and increased the number of exophytic tumors. Increased activity of T cell killers in tumors and higher level of proteins involved with apoptosis following consumption of the orange pulp indicate a clear tumor suppressor effect of these dietary fibers.

Adenocarcinoma↗

Inhibitory effect of lycopene on cataract development in galactosemic rats.

This study investigated the effect of antioxidants on cataract formation in galactosemic rats. Two antioxicants were compared: lycopene, a carotenoid derived from tomato, and butylated hydroxytoluene (BHT), a known antioxidant substance. The control group was fed with galactose 30%. The experimental groups received, in addition to galactose 30%, either lycopene 0.8% or BHT 0.2%. Cataractogenesis was evaluated by the incidence of cataract, grading of cataract, histology of the lenses, aldose reductase (AR) activity, protein levels, and reduced glutathione (GSH) contents in the lens. In both experiemtal groups: 1) the incidence and grading of cataract were lower, 2) the protein levels and GSH content were higher, and 3) the AR was decreased compared to the control group. In conclusion, "natural antioxidants" such as lycopene derived from tomato have a similar effect as BHT in delaying cataractogenesis in rats.

Aldehyde Reductase↗

Tumor-promoting and tumor-protective effects of high-fat diets on chemically induced mammary cancer in rats.

We studied the effects of different dietary fats on experimental rat mammary lumorigenesis induced by 9,10-dimethyl-1, 2-benzanthracene (DMBA). Rats were randomly placed into four groups fed different diets: a chow diet, and high-fat (15%) diets derived from avocado, soybean or olive oils. The rats were killed 12 weeks after treatment with DMBA (a single dvse of 10 mg/rat) and maintenance on these diets. The olive diet was associated with a significant reduction in the tumorigenic effect of DMBA: tumor incidence decreased to 30%, as compared to 44%-55% in the other dietary groups studied (p < 0.05). The protective antitumor effect of the olive diet was found to be connected to its dietary content of monounsaturated fatty acids such as oleic and palmitic acids and with serum concentrations of stearic acid. The promotive tumorigenic effects of the other high-fat diets were associated with their high levels of some polyunsaturated fatty acids (linoleic and alinolenic). Malignant mammary tissue exhibited higher values than benign tissue for all the argyrophilic-nucleolar-organizer region parameters measured. The tumor-associated protein p53 was accumulated to high levels in the blood of tumor-bearing rats, but not in that of the non tumor-bearing rats.

9,10-Dimethyl-1,2-benzanthracene↗

Role of apoptosis, proliferating cell nuclear antigen and p53 protein in chemically induced colon cancer in rats fed corncob fiber treated with the fungus Pleurotus ostreatus.

The role of apoptosis, proliferative cell nuclear antigen (PCNA) and p53 protein in the preventive effects of dietary fiber treated with the fungus Pleurotus ostreatus on rat-colon tumorigenesis was studied. Tumors were induced by five subcutaneous injections of 1,2-dimethylhydrazine (DMH), 20 mg/kg rat, once a week. Rats were fed a semi-synthetic fiberfree diet (control) or a high-fiber diet (15%) derived from corncob treated or non-treated with the fungus. The rats we sacrificed 24 weeks after the first carcinogenic injection. The fungus treated corn-cob significantly decreased tumor incidence (to 26%) as compared to 44% and 57% in the other dietary groups. The apoptotic index (AI) significantly decreased in malignant tissue as compared to non-tumorous tissue. PCNA and cytoplasmic content of p53 protein exhibited an increasing trend in malignant tissue as compared to benign tissue (at 15% and 18%, respectively). The fungus-treated corncob significantly increased the content of p53 in the cell cytoplasm (to 33%) and its serum levels in tumor-bearing rats (to 38%). The cellular concentration of PCNA decreased to 61% in tumors obtained from rats fed the fungus-treated corncob as compared to controls. A high positive correlation was found between tumor grade and p53 protein in the serum (r = 0.97) or in the cell cytoplasm (r = 0.77) and between tumor grade and PCNA (r = 0.81). An inverse relationship was found between tumor grade and AI (r = -0.63). We found that 15% of corncob fiber alone seems not to be enough to prevent chemically induced tumorigenesis. The corncob fiber (15%) treated with the fungus had a significant protective effect against DMH-induced rat colon cancer, even at 15% and this effect was accompanied by the activation of some cellular mechanisms such as apoptosis, PCNA and p53 protein activation. Incubation of corncob with the fungus Pleurotus os, increased the dietary fiber content up to 78%. Thus corncob inhibits colon cancer development, and, therefore, may considered of potential use to the public.

1,2-Dimethylhydrazine↗

Effects of dietary fiber on the rat intestinal mucosa exposed to low doses of a carcinogen.

BACKGROUND: Changes in morphological and immunohistochemical parameters were studied in the rat intestinal mucosa exposed to low doses of a carcinogen and administered with dietary fibers. METHODS: Tumors were induced by five subcutaneous injections of 1,2-dimethylhydrazine, 10 mg/kg rat, once a week. Rats were fed a semi-synthetic fiber-free diet (control) or a high-fiber diets (15%) derived from cellulose, tomato peels or white grape. The rats were sacrificed 24 weeks after the first carcinogen's injection. The ileum, colon and tumors were removed for the study. Areas of the mucosal stroma and of lymph infiltrations, and mitotic index were studied along with morphological parameters. Immunohistochemical parameters included determination of Ki-67 proliferating protein and apoptotic index. RESULTS: Areas of the stroma in colon tumors increased in rats fed tomato peels. Changes in areas of lymphoid infiltrates were related to the type of diet and tumor presence. Lymphoid infiltrations were found to be highly developed in the colon area close to tumors, especially in rats fed the white-grape diet. Mitotic index and Ki-67 protein increased significantly in the colon area close to a tumor and in tumors themselves without any relation to the fiber varieties consumed. Changes in the rate of apoptosis were not related to the preventive effect of diets: apoptotic index was high in tumors obtained from rats fed the high-cellulose diet with high tumor-preventive effects and also from rats fed the high-tomato-peel diet with low tumor-preventive effects. CONCLUSIONS: No morphological changes were found in the ileum of rats exposed to a carcinogen and fed different dietary fibers. In the colon, a carcinogen even in low concentrations inhibited the lymphoid system in the mucosa located far from the tumor or close to the tumor. An increase in the proliferation rate in the colon close to the tumor may reflect the development of precanceromatous processes or may be related to the effect of growth factors expressed by tumor cells. Finding adenoma-like dysplasia near tumors may be possible in early stages of the development of new tumors. In addition, activation of the lymphoid system of the colon following consumption to specific dietary fiber may be a mechanism by which fiber protect against cancer.

1,2-Dimethylhydrazine↗