Feeding a Protective Hydrolysed Casein Diet to Young Diabetes-prone BB Rats Affects Oxidation of L[U?C14] glutamine in Islets and Peyer's Patches,Reduces Abnormally High Mitotic Activity in Mesenteric Lymph Nodes,Enhances Islet Insulin and Tends to Normalize NO Production

The present studies were undertaken to examine concomitant diet-induced changes in pancreatic islets and cells of the gut immune system of diabetes-prone BB rats in the period before classic insulitis. Diabetes-prone (BBdp) and control non-diabetes prone (BBc) BB rats were fed for ~ 17 days either a mainly plant-based standard laboratory rodent diet associated with high diabetes frequency, NIH-07 (NIH) or a protective semipurified diet with hydrolyzed casein (HC) as the amino acid source. By about 7 weeks of age, NIH-fed BBdp rats had lower plasma insulin and insulin/glucose ratio, lower insulin content of isolated islets, lower basal levels of NO but higher responsiveness of NO production to IL-1β in cultured islets, and higher Con A response and biosynthetic activities in mesenteric lymphocytes than control rats fed the same diet. In control rats, the HC diet caused only minor changes in most variables, except for a decrease in oxidation of L-[U−C14]glutamine in Peyer''s patch (PP) cells and an increase in protein biosynthesis in mesenteric lymphocytes. In BBdp rats, however, the HC diet increased plasma insulin concentration, islet insulin/ protein ratio, and tended to normalize the basal and IL-1β-stimulated NO production by cultured islets. The HC diet decreased oxidation of L-[U−C14]glutamine in BBdp pancreatic islets, whereas oxidation of L-[U−C14]glutamine in PP cells was increased, and the basal [Methyl-H3] thymidine incorporation in mesenteric lymphocytes was decreased. These findings are compatible with the view that alteration of nutrient catabolism in islet cells as well as key cells of the gut immune system, particularly changes in mitotic and biosynthetic activities in mesenteric lymphocytes, as well as basal and IL-1β stimulated NO production, participate in the sequence of events leading to autoimmune diabetes in BB rats. Thus, the protection afforded by feeding a hydrolysed casein-based diet derives from alterations in both the target islet tissue and key cells of the gut immune system in this animal model of type 1 diabetes.     

Effect of alpha-phenyl-N-tert-butylnitrone on diabetes and lipid peroxidation in BB rats.

Oxygen free radicals have been shown to interfere with pancreatic islet beta cell function and integrity, and have been implicated in autoimmune type 1 diabetes. We hypothesized that the spontaneous autoimmune type 1 diabetes of the BB rat would be prevented by in vivo administration of a free-radical spin trap, alpha-phenyl-N-tert-butylnitrone (PBN). Twenty-eight diabetes-prone (BBdp) and 13 non-diabetes-prone (BBn) rats received PBN (10 mg/kg) subcutaneously twice daily, and 27 BBdp and 12 BBn rats received saline as controls. Rats were treated from age 47 +/- 6 days until diabetes onset or age 118 +/- 7 days. PBN caused no growth, biochemical, or hematological side effects. Sixteen control BBdp rats became diabetic (BBd, mean age 77 +/- 6 days) and six demonstrated impaired glucose tolerance (IGT rats). The incidence of diabetes and IGT was not different in PBN-treated BBdp rats. Saline-treated rats showed no differences in pancreatic malondialdehyde (MDA) contents of BBd, IGT rats, and the BBdp that did not develop diabetes, versus BBn rats (2.38 +/- 0.35 nmoL/g). Among rats receiving PBN, BBn had lower pancreatic MDA than BBd and IGT rats (1.38 +/- 0.15 vs. 1.88 +/- 0.15 and 2.02 +/- 0.24 nmoL/g, p < 0.05), but not than BBdp rats (1.78 +/- 0.12 nmoL/g, ns). BBn rats receiving PBN also had lower pancreatic MDA than the saline controls (p < 0.05). Thus, PBN is remarkably nontoxic and is able to decrease MDA in the absence of the autoimmune process, but does not prevent diabetes. A combination of PBN with other complementary antioxidant agents may hold better promise for disease prevention.     

Effect of Dietary Vanadium on Cecal Tonsil T Cell Subsets and IL-2 Contents in Broilers

The purpose of this 42-day study was to investigate the effects of dietary excess vanadium on intestinal immune function by histopathological observation of cecal tonsil and changes of the cecal tonsil T cell subsets by method of flow cytometry. Four hundred twenty 1-day-old avian broilers were divided into six groups and fed on a corn-soybean basal diet as control diet or the same diet amended to contain 5, 15, 30, 45, and 60 mg/kg vanadium supplied as ammonium metavanadate. In comparison with those of control group, lymphocytes in the lymphatic nodule of cecal tonsil were apparently decreased in 45 and 60 mg/kg groups. The percentage of CD(3)(+) T cells was decreased (p?相似文献   

Enhanced islet expansion by β‐cell proliferation in young diabetes‐prone rats fed a protective diet

Type 1 diabetes is inhibited in diabetes‐prone BioBreeding (BBdp) rats fed a low‐antigen hydrolyzed casein (HC) diet. In cereal‐fed BBdp rats, islet expansion is defective accompanied by a futile upregulation of islet neogenesis without increased islet mass, due to a subtle blockage in islet cell cycle. We hypothesized that islet growth is enhanced before insulitis in HC‐fed young BBdp rats and that islet neogenesis could be stimulated by a trophic factor, islet neogenesis‐associated protein (INGAP). β‐Cell homeostasis was analyzed using immunohistochemistry, morphometry, laser capture microdissection and RT‐PCR in BBdp rats fed HC or cereal diets. β‐cell proliferation in small and medium islets, and the number and area fraction of medium and large islets were increased in HC‐fed animals. In situ islet cell cycle analysis revealed an increased proportion of proliferating S + G2 cells in medium and large islets of 25–45 day HC‐fed rats. Expression of the cell cycle inhibitor, p16^INK4a correlated with islet size and the percentage of p16^INK4a+ β‐cells increased in HC‐fed BBdp rats, likely reflecting an increase in large islet area fraction. In HC‐fed rats, extra‐islet insulin⁺ clusters (EIC), insulin⁺ duct cells, large islet area fraction, and β‐cell mass were increased. Neurogenin‐3 and Pdx‐1, markers of β‐cell progenitors, were increased in EIC of weanling HC‐fed rats. Daily injection of INGAP (30–45 days) increased the number of small islets, total islets, and insulin⁺ cells in small ducts. Thus, in BBdp rats fed a protective HC diet, β‐cell expansion is enhanced through increased β‐cell proliferation and stimulation of islet neogenesis. J. Cell. Physiol. 224: 501–508, 2010. © 2010 Wiley‐Liss, Inc.     

Effects of Actinomycin D and Cycloheximide on Zinc Status in Marginally Zinc-Deficient Rats

During deficient zinc intake, rats are liable to suffer zinc deficiency under the following conditions: higher protein diet, diet containing higher quality (higher nutritive value) protein, and higher dietary intake. This suggests that a higher protein nutritional status (rapid increase in body protein) in rats leads to a lower zinc nutritional status (higher zinc requirement). In contrast, it is expected that a lower protein nutritional status (lowered body protein biosynthesis) is not liable to result in a lower zinc nutritional status. Therefore, the effects of protein biosynthesis inhibitors on zinc status were studied. Actinomycin D and cycloheximide were administered to rats under a marginally zinc-deficient condition. The growth of rats was depressed and serum and femur zinc concentrations were increased by administration of protein biosynthesis inhibitors. The carcasses of rats administered protein synthesis inhibitors had a higher zinc/protein ratio than those of the respective pair-fed (calorically equivalent to the zinc-deficient group) rats. Results suggest that zinc deficiency in rats is mainly alleviated by decreased food intake with administration of protein synthesis inhibitors. Furthermore, protein biosynthesis inhibition alone alleviated zinc deficiency.     

Depression-like and anxiety-related behaviour of rats fed with magnesium-deficient diet

The aims of this study were to estimate of psychomotor activity, emotional status and magnesium (Mg) content in blood of rats fed with Mg-deficient diet for 49 days; and to find out whether the combination of vitamin B6 with Mg will reveal antidepressant- and anxiolytic-like activity and reduce the length of the treatment needed to recover rats from Mg-deficient condition. To induce hypomagnesemia, seventy-nine rats were placed on a Mg-deficient diet (Mg content < or = 15 mg/kg) and demineralized water for 7 weeks. Eight control rats were fed a basal control diet. On the forty-ninth day of Mg-deficient diet, rats were treated one of the six supplementations: Mg L-aspartate alone and in combination with pyridoxine, MgCl2 x 6H2O alone and in combination with pyridoxine, Magne B6 (Mg lactate with pyridoxine) and Mg sulfate (50 mg Mg and 5 mg vitamin B6 per kg). In our study Mg-deficiency was associated with depleted intraerythrocytic (0.748 +/- 0.036 vs. 1.83 +/- 0.026 mmol/l, p < 0.001) and plasma (0.567 +/- 0.029 vs. 1.20 +/- 0.030 mmol/l, p < 0.001) Mg level compared to control rats. It was shown Mg deficiency resulted in depression-like and anxiety-related behavior in rats. Open field test result in rats including locomotor activity (number of crossed squares) and vertical activity (number of standing on hind paws), number of visiting in central squares were decreased significantly. In the elevated plus maze test, the number of visiting open arms (by 63.6%) and residence time (by 78.5%) of rats were significantly less as compared with the control group. In the forced swimming test, time immobile was significantly increased (by 70.2%) and time of swimming was decreased (by 15%) compared to control. Mg salts alone and in combination with vitamin B6 administered to Mg-deficient rats increased the Mg level in plasma and erythrocytes. Furthermore, this increase was in relation to vitamin B6 given to the animal. It was established, that the application of Mg L-aspartate and MgCl2 x 6H2O in combinations with pyridoxine led to correction of behavioural disturbances of Mg-deficient animals. Antidepressant- and anxiolytic-like activity of studied salts was comparable with those observed in Magne B6 treatment and significantly higher than in Mg sulfate treatment.     

Iron and zinc status in rats with diet-induced marginal deficiency of vitamin A and/or copper

The hypothesis was tested that there are interactions of marginal copper and vitamin A deficiency regarding iron and zinc status. Copper restriction (1 vs 5 mg Cu/kg diet) significantly lowered copper concentrations in plasma and tissues of rats and reduced blood hemoglobin, hematocrit, and iron concentrations in tibia and femur, but raised iron concentrations in liver. Vitamin A restriction (0 vs 4000 IU vitamin A/kg diet) reduced plasma retinol concentrations and induced a fall of blood hemoglobin and hematocrit. Neither copper nor vitamin A restriction for up to 42 d affected feed intake and body wt gain. There were no interrelated effects of vitamin A and copper deficiency on iron status. Copper deficiency slightly depressed liver, spleen, and kidney zinc concentrations. Vitamin A deficiency lowered zinc concentrations in heart, but only when the diets were deficient in copper.     

Vitamin D Supplementation Modulates Blood and Tissue Zinc, Liver Glutathione and Blood Biochemical Parameters in Diabetic Rats on a Zinc-Deficient Diet

Previous studies suggest a protective effect of vitamin D3 on zinc deficiency-induced insulin secretion and on pancreas β-cell function. The aim of this study was to investigate the effect of vitamin D on blood biochemical parameters, tissue zinc and liver glutathione in diabetic rats fed a zinc-deficient diet. For that purpose, Alloxan-induced diabetic rats were divided into four groups. The first group was fed a zinc-sufficient diet while the second group was fed a zinc-deficient diet. The third and fourth groups received zinc-sufficient or zinc-deficient diets plus oral vitamin D3 for 27 days. At the end of the experiment, blood, femur, pancreas, kidney and liver samples were taken from all rats. The serum, femur, pancreas, kidney and liver zinc concentrations, liver glutathione, serum alkaline phosphatase activity, daily body weight gain and food intake were lower in the zinc-deficient rats in comparison with those receiving adequate amounts of zinc. These values were increased in the zinc-deficient group that was supplemented with vitamin D3. The serum total cholesterol, triglycerides, total protein, urea, glutamate oxaloacetate transaminase, glutamate pyruvate transaminase and blood glucose values were higher in rats fed a zinc adequate diet, but their concentrations were decreased by vitamin D3 supplementation. The serum total protein levels were not changed by zinc deficiency and vitamin D3 supplementation. These results suggest that vitamin D3 modulates tissue zinc, liver glutathione and blood biochemical values in diabetic rats fed a zinc-deficient diet.     

Supplemental zinc and vitamin A can alleviate negative effects of heat stress in broiler chickens

This experiment was conducted to evaluate the effects of zinc (ZnSO₄H₂O) and vitamin A (retinol) supplementation on performance, carcass characteristics, and serum concentrations of glucose, cholesterol, total protein, and malondialdehyde (MDA) as an indicator of lipid peroxidation in broiler chickens (Ross) reared at a high temperature (34°C). One hundred twenty 10-d-old male broilers were randomly assigned to 4 treatment groups, 3 replicates of 10 birds each. The birds were fed either a basal diet or the basal diet supplemented with either 30 mg Zn/kg diet, 4.5 mg (15,000 IU) retinol/kg diet, or 30 mg Zn+4.5 mg retinol/kg diet. Supplemental zinc and vitamin A significantly increased live weight gain and improved feed efficiency (p<0.05). However, a combination of zinc and vitamin A, rather than each separately, provided a greater performance. Hot and chilled carcass weights and yields and the weights of internal organs with the exception of abdominal fat were greater for each supplement (p<0.05) compared to the control group. Abdominal fat decreased (p<0.05) upon dietary zinc and vitamin A supplementation. Supplemental treatments resulted in an increased total serum protein but decreased glucose, cholesterol, and MDA concentrations. The results of the study show that, separtely or as a combination, zinc and vitamin A supplementation resulted in an improved live weight gain, feed efficiency, and carcass traits, as well as a decrease in serum MDA concentrations. The results of the present study also suggest that zinc and vitamin A have similar effects and that a combination of zinc and vitamin A may offer a potential protective management practice in preventing heat-stress-related depression in performance of broiler chickens.     

Potential therapeutic effect of antioxidants in experimental diabetic retina: a comparison between chronic taurine and vitamin E plus selenium supplementations

Although good glycaemic control can delay the development and progression of diabetic retinopathy, new therapies are needed to obtain a better control of this diabetic complication. Oxidative stress seems to be a contributing factor in diabetic retinal alterations, therefore, it has been suggested that antioxidants may be beneficial in reducing diabetic retinal changes. However, many questions are still open. In fact, it remains to be ascertained which antioxidants are the most active when they are chronically administered in vivo and their effective dosages. Therefore, we compared the effect of chronic taurine supplementations versus a mixture of vitamin E + selenium on biochemical retinal changes induced by diabetes at different stages of the disease. Briefly, streptozotocin (STZ) diabetic rats were administered for 4 months following the dietary supplements: (a) 2% (w/w) taurine; (b) 5% (w/w) taurine; (c) 200 IU vitamin E + 8 mg selenium/kg diet (d) 500 IU vitamin E + 8 mg selenium/kg diet. In STZ diabetic rat in poor metabolic control (i.e. serum glucose >16.5 mmol/l), at 2, 4, 8, 16 weeks following the onset of diabetes, retinal conjugated dienes (CD) and lipid hydroperoxides (LP) were significantly and progressively increased, while sodium pump activity was gradually and significantly reduced. In taurine and vitamin E + selenium supplemented diabetic rats, glycaemia and body weight were not significantly different from those of non-supplemented diabetic animals. In diabetic rats, 2 and 5% taurine significantly decreased CD. This reduction is long lasting. Regarding CD, both vitamin E + selenium supplementations reduced CD only during the first 4 weeks of diabetes. Two percent taurine supplementation significantly lowered LP for the first 8 weeks of the disease while 5% taurine-induced-reduction lasted for the whole experimental time. A 200 IU vitamin E + 8 mg selenium supplementation did not significantly modify LP, while 500 IU vitamin E + 8 mg selenium significantly lowered them for the whole studied period. Finally, taurine preserved ATPase activity being more effective at 5% than 2%. Two hundred IU vitamin E + 8 mg selenium did not generally modify pump activity, while 500 IU vitamin E + 8 mg selenium partially prevented the decrease in pump activity. We conclude that taurine and vitamin E + selenium supplementations ameliorate biochemical retinal abnormalities caused by diabetes. These effects are dose- and time-dependent Moreover, the effect of taurine on CD is longer lasting than that of vitamin E + selenium. In addition, taurine seems to better preserve ATPase activity in comparison with vitamin E + selenium. Finally, in diabetic animals a negative correlation is found between CD and LP on one side and Na+K+ATPase activity on the other; thus, lipid peroxidation and pump activity seem to be associated. The same inverse correlations are present in vitamin E + selenium supplemented diabetic rats, but are lost in taurine supplemented animals. Therefore, taurine effects may not be simply mediated by its antioxidant activity. Thus, chronical (4 months) taurine and vitamin E + selenium supplementations reduce biochemical retinal alterations in diabetic rat in poor metabolic control.     

Pentose phosphate pathway,glutathione-dependent enzymes and antioxidant defense during oxidative stress in diabetic rodent brain and peripheral organs: effects of stobadine and vitamin E

The aim of the present study was to investigate the effects of treatment with antioxidant stobadine (ST) on the activities of enzymes related with pentose phosphate pathway and glutathione-dependent metabolism and the other markers of oxidative stress in brain and peripheral organs of diabetic rats, and to compare the effects of ST treatment alone with the effects of treatments with another antioxidant vitamin E and ST plus vitamin E. Rats were made diabetic by the injection of streptozotocin (STZ; 55 mg/kg IP), and, 2 days later, some control and diabetic rats were left untreated or treated with ST (24.7 mg/kg/day, orally), vitamin E (400–500 U/kg/day, orally), or both substances together. In the brain, although 6-phosphogluconate dehydrogenase activity (6-PGD) did not change, glucose-6-phosphate dehydrogenase activity (G-6PD) was markedly increased in diabetic rats compared with controls; only combined treatment with ST and vitamin E produced a partial prevention on this alteration. The aorta G-6PD and 6-PGD of diabetic rats were 52% and 36% of control values, respectively. Neither single treatments with each antioxidant nor their combination altered the G-6PD and 6-PGD in aorta of diabetic rats. Glutathione peroxidase (GSHPx) activity was increased by STZ-diabetes in brain, heart, and kidney. In diabetic brain, vitamin E alone or combination with ST kept GSHPx at normal levels. Diabetes-induced stimulation in GSHPx did not decrease in response to the treatment with vitamin E in heart and kidney, but was greatly prevented by ST alone. The activity of glutathione reductase (GR) was decreased in brain and heart of diabetic rats. The treatment with each antioxidant or with a combination of both agents completely prevented this deficiency and resulted in further activation of GR in diabetic tissues. Glutathione S-transferase (GST) activity did not significantly change in diabetic brain and aorta. GST was stimulated by all treatment protocols in the brain of diabetic rats and was depressed in aorta of control rats. Catalase (CAT) was activated in diabetic heart but depressed in diabetic kidney. Diabetes-induced abnormalities in CAT activity did not respond to vitamin E alone in heart, was moderately ameliorated by the treatment with this vitamin in kidney, and was completely prevented by ST alone in both tissues. Superoxide dismutase (SOD) activity of brain and heart was unchanged by the diabetes but inhibited in diabetic kidney after the treatment ST alone or ST plus vitamin E. The lipid peroxidation (MDA) was increased in diabetic brain and heart. ST or vitamin E alone partly prevented diabetes-induced increase in MDA in brain and heart; however, antioxidant combination achieved a completely amelioration in MDA of these tissues of diabetic rats. Kidney MDA levels were similar in control and untreated diabetic animals. ST and vitamin E treatments, when applied separately or together, significantly reduced kidney MDA in both control and diabetic rats; and the combined effect of antioxidants was greater than that of each alone. These results are consistent with the degenerative role of hyperglycemia on cellular reducing equivalent homeostasis and antioxidant defense, and provide further evidence that pharmacological intervention of different antioxidants may have significant implications in the prevention of the prooxidant feature of diabetes and protects redox status of the cells.     

Low zinc intake decreases the lymphatic output of retinol in rats infused intraduodenally with beta-carotene

Previously, we have shown that the lymphatic absorption of retinol is significantly decreased in rats fed a low zinc diet. This study was conducted to determine whether the absorption of beta-carotene also is altered in zinc-deficient male rats. The absorption of beta-carotene was estimated by determining the amount of retinol appearing in the mesenteric lymph during intraduodenal infusion of beta-carotene. One group of rats was fed the AIN-93G diet but low in zinc (LZ; 3 mg/kg) and the other was fed the same diet adequate in zinc (AZ; 30 mg/kg). The LZ and AZ rats were trained to meal feed equal amounts of the diets twice daily. At 6 weeks, each rat with lymph cannula was infused via an intraduodenal catheter at 3 ml/h for 8 h with a lipid emulsion containing 65.0 nM beta-carotene, 565.1 microM triolein, 27.8 kBq 14C-triolein (14C-OA), 72 mg albumin, and 396 microM Na-taurocholate in 24 ml PBS (pH 6.7). The lymphatic output of retinol over the 8-h period was significantly lower in LZ rats than in AZ rats. The absorption of 14C-OA also was significantly lower in LZ rats. No significant differences were observed between groups in intestinal beta-carotene 15,15'-dioxygenase, retinal reductase, and retinal oxidase activities. The findings demonstrate that low zinc intake or marginal zinc deficiency significantly lowers the absorption of beta-carotene as estimated by lymphatic retinol output. The results also indicate that the decrease in retinol output in LZ rats is not linked to defects in beta-carotene cleavage and subsequent conversion of retinal to retinol in the intestinal mucosa. This study suggests that zinc status is an important factor determining the intestinal absorption of beta-carotene and hence the nutritional status of vitamin A.     

Testicular atrophy, zinc concentration, and angiotensin-converting enzyme activity in the testes of vitamin a-deficient rats

Angiotensin-converting enzyme (ACE) as a part of the renin angiotensin system (RES) regulates blood pressure and fluid and electrolyte homeostasis, and the enzyme is considered to have a function in reproduction. Reduced enzyme activities have been observed in atrophied testes as a results of zinc and pituitary deficiencies. Vitamin A deficiency causes atrophy of testes. The present study was conducted on three groups of male, 3-wk-old, Wistar rats. After 54 d of the experimental period, testicular weights of the vitamin A-deficient rats (Agroup, allowed free access to vitamin Adeficient diet) was significantly lower than its pair-fed, PF (given restricted amount control diet) and A+ (allowed free access to control diet) groups. Zinc concentrations and both soluble and particulate ACE activities in the testes of vitamin A-deficient rats (Agroup) were significantly lower than the other two groups. No significant differences were observed regarding zinc concentration, particulate ACE, and total ACE activities in the testes of PF and A+ groups. Vitamin A deficiency did not significantly affect the enzyme activity in the lung. From the observations of the present study, we speculate that testicular atrophy in vitamin A deficiency may have resulted from lower zinc concentration and decreased ACE activity in that organ.     

Changes in some innate defence parameters of seabream (Sparus aurata L.) induced by retinol acetate

The effects of high doses of dietary or intraperitoneally (i.p.) injected retinol acetate on the gilthead seabream (Sparus aurata L.) innate immune system were studied. Gilthead seabream specimens were fed a commercial non-supplemented diet containing 1.75 mg of vitamin A kg(-1) (as control) or the same diet supplemented with 50, 150 or 300 mg of retinol acetate kg(-1) (as vitamin A source). After 1, 2, 4 or 6 weeks, serum samples and head-kidney leucocytes were obtained from each fish. Serum lysozyme activity and myeloperoxidase (MPO) content were unaffected by the vitamin A diet content. The phagocytic and respiratory burst activities of head-kidney leucocytes were established, as well as their myeloperoxidase content. While phagocytosis was not enhanced by dietary vitamin A intake and was even slightly decreased after 2 weeks, respiratory burst activity was enhanced in specimens fed supplements of 150 and 300 mg retinol acetate kg(-1) diet for 1 or 2 weeks. Leucocyte MPO content was also enhanced when seabream were fed the highest vitamin A dose for 2 or 4 weeks and after being fed the 150 or 50 mg supplemented diets for 4 or 6 weeks, respectively. Three different groups of seabream were i.p. injected with 1 ml of phosphate buffer containing an amount of retinol acetate equivalent to the daily dietary supplements from the first experiment (0-control-, 0.05 or 0.30 mg 100 g(-1) biomass). Both injection doses of retinol acetate were toxic for the gilthead seabream which showed hypervitaminic effects. These data show that retinol acetate plays an important role in the gilthead seabream nonspecific cellular immune system due to its antioxidant properties. They also point to the importance of the way in which it is administered, by dietary uptake or intraperitoneal injection.     

Feeding of a low-zinc diet lowers the tissue concentrations of alpha-tocopherol in adult rats

Previous work has shown that a low dietary intake of zinc for a short duration significantly lowers the lymphatic absorption of α-tocopherol (αTP) in adult male rats. The present study investigated whether the nutritional status of zinc is critical in maintaining the tissue levels of the vitamin. One group of rats was fed an AIN-93G diet containing 3 mg zinc/kg (low zinc, LZ) and the other was fed the same diet but containing 30 mg zinc/kg (adequate zinc, AZ). Food intakes between groups were matched by feeding two meals per day. At 6 wk, the body weights (356±8 g) of LZ rats reached 98% those (362±10 g) of AZ rats. Feeding of the LZ diet for 6 wk significantly lowered the concentrations of both αTP and zinc in the liver, kidney, heart, testis, and brain. No consistent relationships between αTP and zinc concentrations were observed in other tissues such as spleen, lung, gastrocnemius muscle, and retroperitoneal fat tissues. The concentrations of αTP in the liver, testis, brain, spleen, heart, and kidney were significantly correlated with the tissue concentrations of zinc. The LZ diet slightly but significantly increased the total lipid contents (mg/g) of liver, kidney, heart, and spleen. However, the tissue levels of phospholipid (μmol/100 mg lipid) in the heart, lung, testis, and spleen were decreased significantly in LZ rats. These findings indicate that low zinc intake results in a pronounced decrease in the animal’s αTP status under the conditions of matched food intakes, body weights, and feeding patterns. The lower tissue levels of αTP may explain in part the compromised antioxidant defense system and increased susceptibility to oxidative damage observed in zinc deficiency.     

Dietary vitamin B12, sulfur amino acids,and odd-chain fatty acids affect the response of rats to nickel deprivation

An experiment was performed to ascertain whether changing the dietary intake of two substances, cystine and margaric acid (heptadecanoic acid), that affect the flux through pathways involving the two vitamin B₁₂-depednent enzymes, methionine synthase and methylmalonyl-CoA mutase, would affect the interaction between nickel and vitamin B₁₂. Rats were assigned to treatment groups of six in a fully crossed, four-factorial arrangement. The independent variables, or factors, were: per kg of fresh diet, nickel analyzed at 25 and 850 μg; vitamin B₁₂ supplements of 0 and 50 μg; margaric acid supplements of 0 and 5 g; andl-cystine supplements of 0 and 12 g. The diet without cystine was marginally deficient in sulfur amino acids. Nickel affected growth, liver wt/body wt ratio (LB/BW), and a number of variables associated with iron, calcium, zinc, copper, and magnesium metabolism. Most of the effects of nickel were modified by the vitamin B₁₂ status of the rat. In numerous cases, the interaction between nickel and vitamin B₁₂ was dependent on, or altered by, the cystine or margaric acid content of the diet. Thus, the findings showed that the extent and the direction of changes in numerous variables in response to nickel deprivation varied greatly with changes in diet composition. These variables include those previously reported to be affected by nickel deprivation, including growth and the distribution or functioning of iron, calcium, zinc, copper, and magnesium. The findings also support the hypothesis that nickel has a biological function in a metabolic pathway in which vitamin B₁₂ is important.     

Oxidative stress as a mechanism of diabetes in diabetic BB prone rats: Effect of secoisolariciresinol diglucoside (SDG)

Secoisolariciresinol diglucoside (SDG) isolated from flaxseed has antioxidant activity and has been shown to prevent hypercholesterolemic atherosclerosis. An investigation was made of the effects of SDG on the development of diabetes in diabetic prone BioBreeding rats (BBdp rats), a model of human type I diabetes [insulin dependent diabetes mellitus (IDDM)] to determine if this type of diabetes is due to oxidative stress and if SDG can prevent the incidence of diabetes. The rats were divided into three groups: Group I, BioBreeding normal rats (BBn rats) (n = 10); group II, BBdp untreated (n = 11); and group III, BBdp treated with SDG 22 mg/kg body wt, orally) (n = 14). Oxidative stress was determined by measuring lipid peroxidation product malondialdehyde (MDA) an index of level of reactive oxygen species in blood and pancreas; and pancreatic chemiluminescence (Pancreatic-CL), a measure of antioxidant reserve. Incidence of diabetes was 72.7% in untreated and 21.4% in SDG-treated group as determined by glycosuria and hyperglycemia. SDG prevented the development of diabetes by approximately 71%. Development of diabetes was associated with an increase in serum and pancreatic MDA and a decrease in antioxidant reserve. Prevention in development of diabetes by SDG was associated with a decrease in serum and pancreatic-MDA and an increase in antioxidant reserve. These results suggest that IDDM is mediated through oxidative stress and that SDG prevents the development of diabetes.     

The Effects of l-Arginine, Alone and Combined with Vitamin C, on Mineral Status in Relation to its Antidiabetic, Anti-Inflammatory, and Antioxidant Properties in Male Rats on a High-Fat Diet

The aim of this study was to evaluate the influence of the intake of l-arginine alone and of l-arginine with vitamin C on mineral concentration in rats fed with a high-fat diet, and to assess the lipid glucose, insulin, and total antioxidant status (TAS) and tumor necrosis factor (TNF) alpha serum levels that result. Wistar rats were assigned to groups fed with either a standard control diet (C), a diet high in fat (FD), a diet high in fat with l-arginine, or a diet high in fat with l-arginine and vitamin C. After 6 weeks, the length and weight of the rats were measured, and the animals were euthanized. The liver, spleen, kidneys, pancreas, heart, and gonads were collected, as were blood samples. The total serum cholesterol, triglyceride, fasting glucose, insulin, TAS, and TNF alpha levels were measured. The tissue calcium, magnesium, iron, zinc, and copper concentrations were determined. It was found that l-arginine supplementation diminished the effect of the modified diet on the concentration of iron in the liver and spleen and of copper in heart. At the same time, it was observed that l-arginine supplementation reduced the effect of the high-fat diet on insulin, TNF alpha, and TAS. The combination of l-arginine and vitamin C produced a similar effect on the mineral levels in the tissues as did l-arginine used alone. Moreover, positive correlations between serum insulin and iron in the liver, between TNF alpha and iron in the liver, and between TNF alpha and copper in the heart were observed. The level of TAS in serum was inversely correlated with the copper level in the heart and the iron level in the liver. We concluded that the beneficial influence of l-arginine on insulin, TAS, and TNF alpha serum level is associated with changes in the iron and copper status in rats fed with a high-fat diet. No synergistic effect of l-arginine and vitamin C in the biochemical parameters or in the mineral status in rats fed with the modified diet was observed.     

The impact of iron content in a diet high in fat,fructose, and salt on metabolic state and mineral status of rats

The purpose of the study was to assess the influence of dietary iron content on lipid and carbohydrate metabolism and on zinc and copper status in rats fed with a diet high in fat, fructose, and salt. Wistar rats were fed with diets high in fat, fructose, and salt, containing differing amounts of iron, namely, deficit, normal, and high levels. After 6 weeks, the animals were weighed and killed. The liver, heart, and pancreas were collected, as were blood samples. The total cholesterol, triglycerides, fasting glucose, and insulin levels in the serum were measured. The iron, zinc, and copper concentrations in tissues and serum were determined. It was found that in rats fed with the iron-deficit diet, cholesterol and glucose profiles improved. Both deficit and excess iron in the diet decreased insulin concentration in rats and disturbed iron, zinc, and copper status. High-iron level in the diet decreased the relative mass of the pancreas. In conclusion, the decrease in serum insulin concentration observed in rats fed with the modified diet high in iron was associated with iron and copper status disorders, and also, with a relatively diminished pancreas mass. A deficit of iron in the diet improved lipid and carbohydrate metabolism in rats.     

Tissue antioxidant status in streptozotocin-induced diabetes in rats

Interactions between manganese (Mn) deficiency and streptozotocin (STZ)-diabetes with respect to tissue antioxidant status were investigated in male, Sprague-Dawley rats. All rats were fed either a Mn-deficient (1 ppm) or a Mn-sufficient (45 ppm) diet for 8 wk. Diabetes was then induced by tail-vein injection of STZ (60 mg/kg body weight), after which the rats were kept for an additional 4 or 8 wk. The control groups comprised rats not injected with STZ and fed either Mn-deficient or Mn-sufficient diets for a total of 12 wk. The Mn-deficient diet decreased the activities of manganese superoxide dismutase (MnSOD) in kidney and heart, and of copperzinc superoxide dismutase (CuZnSOD) in kidney, in the non-diabetic animals. In the diabetic rats, the Mn-deficient diet induced more pronounced decreases in activities of these same enzymes, and also increased liver MnSOD activity. Plasma and hepatic vitamin E levels increased progressively with the duration of diabetes, independent of dietary Mn intake. Lipid peroxidation, as measured by H₂O₂-induced production of thiobarbituric acid reactive substances in erythrocytes, also increased, concomitant with decreased liver and kidney glutathione (GSH) levels. These findings demonstrate for the first time an interactive effective between Mn deficiency and STZ-diabetes, resulting in amplification of tissue antioxidant changes seen with either Mn deficiency or STZ-diabetes alone. This effect of Mn deprivation in experimental diabetes suggests a physiological role for Mn as an antioxidant nutrient.