Subcellular distribution of selenium in the liver from rats fed selenium from fish: selenocystine and inorganic selenite

Four groups of rats of a normal selenium status were given different selenium compounds during a long-term feeding experiment (28 days). The selenium supplementations (per kg diet) were sodium selenite (1 mg), selenocystine (2 mg), and two different concentration levels of selenium from fish (0.1 and 1 mg). Differential pelleting of liver homogenates demonstrated that selenium was present in all the subcellular fractions, with a recovery of 55-60% in the cytosols. Gel permeation high-performance liquid chromatography of the cytosol fractions demonstrated the presence of protein-bound selenium at a molecular weight of 70,000 daltons. The subcellular distributions as well as the protein binding of selenium in the cytosols were identical in all dietary groups. This indicates a similar long-term liver metabolism of the four selenium compounds tested in the rat.     

Bioavailability of iron from a traditional Tunisian meal with chickpeas fed to healthy rats.

The influence of a diet of couscous with chickpeas, a traditional Tunisian meal, or one providing iron as ferrous sulfate, on the utilization of 59Fe was evaluated in studies with rats. The iron content of the couscous and chickpea preparation was 30 mg/kg dry weight. There was no difference in the relative absorption of iron from ferrous sulfate or couscous with chickpeas, suggesting that iron from this preparation may be a good dietary source of nonheme iron for rats. Couscous and chickpeas consumption in Tunisia are estimated at 13.3 and 3.2 kg per capita/year, respectively. Our results in rats indicate that these foods could contribute a large proportion of an individual's iron requirement. We conclude that the plant foods, especially the chickpeas, can be excellent sources of dietary-available iron.     

Effects of various dietary selenium intakes on the levels of blood glutathione-peroxidase and selenium in long-term fed rats

Female Sprague-Dawley rats were fed a torula diet or wheat diets containing 4 levels of Se partially supplemented (24-402 ppb) for 120 days. Selenium content and glutathione-peroxidase (GSH-Px) activity in plasma and erythrocytes were measured every 20 days. In rats fed torula diet or basal wheat diet, plasma Se (P-Se) increased for up to 60 days, then remained constant, while erythrocytes Se (E-Se) and E-GSH-Px decreased in basal-diet rats during the first 40-60 days, then increased. In rats fed supplemented diets, P-Se and P-GSH-Px increased more rapidly than E-Se and E-GSH-Px, plateauing at 60-80 days. The best correlation was found between P-GSH-Px and dietary Se indicating that this index is the most sensitive for evaluating changes resulting from different Se intakes. In addition, correlations became more significant with time. The results from rats fed a low Se diet suggest the existence of regulatory mechanisms working in different ways and at different times in plasma and erythrocytes.     

Comparative effect of selenate and selenite on serum selenium concentration and glutathione peroxidase activity in selenium-depleted rats

The biological effect of selenate and selenite was compared in selenium-depleted rats by using both serum selenium concentration and glutathione peroxidase activity as an indicator of body selenium status. A single oral dose of selenium (125 micrograms/kg body weight) as sodium selenate or sodium selenite increased serum selenium concentration and glutathione peroxidase activity significantly (p less than 0.001). The effect of selenate and selenite on serum selenium and glutathione peroxidase activity was similar. Serum selenium concentration correlated positively with serum glutathione peroxidase activity both before (r = 0.815; p less than 0.001) and after (r = 0.800; p less than 0.001) treatment. These results indicate that the biological availability of selenate and selenite is similar.     

Effects of various doses of sodium dichloroacetate on hyperlactatemia in fed ischemic rats

In shock, the presence of hyperlactatemia is prognostic of a failure to survive. An experimental model of stroke that combines bilateral carotid ligation and bleeding to a mean arterial pressure of 50 mm Hg induces hyperlactatemia like that associated with tissue hypoperfusion of hemorrhagic shock. In previous nonsurvival studies with this model, post-ischemic treatment of fed rats with 25 mg/kg of sodium dichloroacetate (DCA) was effective in lowering brain tissue lactate but did not significantly affect the ischemia-induced increase in serum lactate measured after 30 minutes of ischemia followed by 30 minutes of reperfusion. Investigators using other animal models treated hyperlactatemia associated with tissue hypoperfusion successfully with a DCA dose of more than 25 mg/kg. Our goal was to determine the effect of a higher dose of DCA on serum lactate in the model of cerebral ischemia with systemic hypotension that we had used in previous studies. The previously unstudied dose-response also was evaluated in our study. Rats that had been fed ad libitum were assigned randomly to either a real or sham (control) ischemic group. Immediately after 30 minutes of ischemia and subsequent reinfusion of blood or after 30 minutes of sham ischemia, rats received DCA (0, 25, 50, 100, 200, or 300 mg/kg). Comparisons were made of blood values measured at the end of equilibration before ischemia, after 30 minutes of ischemia, and after 30 minutes of reperfusion. All ischemic rats were hyperlactatemic. Serum lactate levels were not correlated to blood glucose elevation during ischemia. After treatment in both control and ischemic rats, the percentage decrease in serum lactate varied as a logarithmic function of the DCA dose administered. Glucose levels and pH were not affected by DCA treatment at any dose. Because acidemia decreases lactate uptake by the liver, values for acidotic rats were compared with those for nonacidotic rats. Whereas lactate in acidotic rats decreased significantly only when treated with DCA, nonacidotic rats evidenced this decrease regardless of whether they received DCA. We discuss the relationship of these findings to the peak levels of lactate achieved, the resolution of hyperlactatemia, and factors that affect the interpretation of data in therapeutic studies using DCA.     

氟斑牙患者服硒后体内氟和抗氧化酶类的变化

测试了氟斑牙患者服亚硒酸钠前后血、尿、发Ｓｅ和血、尿Ｆ－，血液谷胱甘肽过氧化物酶（ＧＳＨ—Ｐｘ），超氧化物歧化酶（ＳＯＤ）和血清脂质过氧化物（ＬＰＯ）。结果血、尿、发Ｓｅ含量升高，血Ｆ－降低，尿Ｆ－排泄增加，血液ＧＳＨ—Ｐｘ、ＳＯＤ活性增强，ＬＰＯ含量下降，血ＧＳＨ—Ｐｘ／ＬＰＯ和ＳＯＤ／ＬＰＯ比值升高．表明硒可拮抗体内高氟，血液抗氧化酶类活性增强。本文就其相互关系以及在氟中毒发病中的作用进行了讨论。     

硒对大鼠急性缺血心肌溶酶体膜的影响

结扎大鼠冠状动脉，造成急性心肌梗塞模型，观察硒对缺血心肌溶酶体酶的影响．结果表明，心肌缺血１小时后，缺血区心肌溶酶体酸性磷酸酶（ＡＣＰ）、组织蛋白酶Ｄ（ＣＤ）的游离酶活性（Ｆ）及游离酶活性／总酶活性比值（Ｆ／Ｔ）均明显升高，ＧＳｌｌ－Ｐｘ活性显著降低，脂质过氧化物含量（ＭＤＡ）明显增加。硒预处理大鼠，心肌急性缺血后．Ｆ及Ｆ／Ｔ显著下降，ＧＳＨ－Ｐｘ明显升高，ＭＤＡ含量显著降低。硒可能通过提高缺血心肌ＧＳＨ－Ｐｘ活性，阻止自由基介导的脂质过氧化，增加溶酶体膜的稳定性，从而减轻心肌缺血性损伤。     

Direct detection of potential selenium delivery proteins by using an Escherichia coli strain unable to incorporate selenium from selenite into proteins

Selenium can be metabolized for protein synthesis by two major pathways in vivo. In a specific pathway it can be inserted into polypeptide chains as the amino acid selenocysteine, as directed by the UGA codon. Alternatively, selenium can be substituted for sulfur to generate the free amino acids selenocysteine and selenomethionine, and these are incorporated nonspecifically into proteins in place of cysteine and methionine, respectively. A mutant strain of Escherichia coli was constructed that is deficient in utilization of inorganic selenium for both specific and nonspecific pathways of selenoprotein synthesis. Disruption of the cysK gene prevented synthesis of free cysteine and selenocysteine from inorganic S and Se precursors. Inactivation of the selD gene prevented synthesis of selenophosphate, the reactive selenium donor, required for the specific incorporation pathway. As expected, the double mutant strain, RL165 Delta selD, when grown anaerobically in LB + glucose medium containing (75)SeO(3)(2-), failed to synthesize selenium-dependent formate dehydrogenase H and seleno-tRNAs. However, it incorporated 24% as much selenium as the wild-type strain. Selenium in the deficient strain was bound to five different proteins. A 39-kDa species was identified as glyceraldehyde-3-phosphate dehydrogenase. It is possible that selenium was bound as a perselenide derivative to the reactive cysteine residue of this enzyme. A 28-kDa protein identified as deoxyribose phosphate aldolase also contained bound selenium. These (75)Se-labeled proteins may have alternate roles as selenium delivery proteins.     

The effect of sodium selenite on chondrocytes in monolayer culture

The effect of sodium selenite on DNA and sulfated proteoglycan synthesis by cultured rabbit articular and growth plate chondrocytes was studied as an in vitro model for Kashin-Beck disease. The selenium content of a defined medium (DMEM, fibroblast growth factor, insulin, and dexamethasone) was below the limit of detection by isotope dilution mass spectrometry. The chondrocytes were viable in the Se-free basal medium. Selenite over a range of 5 X 10(-9) M to 5 X 10(-7) M had no stimulatory effect on DNA or sulfated proteoglycan synthesis by either type of chondrocyte or skin fibroblasts. Proliferation of bovine endothelial cells was enhanced by 5 X 10(-7) M Se. At Se concentrations of greater than or equal to 10(-6) M, there was progressive inhibition of cell growth and radiosulfate incorporation of the connective tissue cells; bovine endothelial cells were more resistant. Twice equimolar concentrations of vitamins C and E exerted no protective effect against the cytotoxicity of higher concentrations of Se. Se supplementation also failed to stimulate growth of human infant chondrocytes. The model enabled simulation of conditions of hyposelenosis below those encountered in nature. The data provide no evidence that chondrocytes have idiosyncratic requirements for Se, and do not support the hypothesis that Se deficiency is a major etiologic factor in Kashin-Beck disease.     

Blood constituents and hepatic lipids in rats fed sucrose or starch with or without cyclamate

To study the effect of type of dietary carbohydrate and cyclamate on selected tissue components, rats were fed basal diets that contained sucrose or cornstarch: dextrin (2:1) with 0, 2, or 10% calcium cyclamate. Substitution of starch:dextrin for sucrose in the basal diet did not significantly affect the concentrations of blood hemoglobin, serum protein, cholesterol or total lipids in liver, or weight gain of the animals. Substitution of 2% cyclamate for sucrose did not appear to affect significantly the parameters studied, except that liver weight and total amino acid concentration decreased. Animals fed starch:dextrin with 2% cyclamate had lower weight gains than those of their respective controls, whereas liver cholesterol and total lipid concentrations were increased. Dietary cyclamate decreased the liver weight of all experimental groups. Weight gains of animals fed sucrose or starch:dextrin with 10% cyclamate in replacement of carbohydrate were, respectively, 41 and 58% lower than those of their respective controls. Substitution of 10% cyclamate for sucrose or starch:dextrin decreased blood hemoglobin. The total concentration of essential amino acids in sera of rats fed 10% cyclamate with sucrose or starch:dextrin approached or exceeded that of the respective controls. The data indicate that the effect of cyclamates on the level of certain tissue components may be related to the type of carbohydrate fed with cyclamate.     

Noninsulin-like action of sodium orthovanadate in the isolated perfused liver of fed,non-diabetic rats

Summary Vanadium compounds exert insulin-like effects on isolated rat adipocytes and skeletal muscle and improve glucose homeostasis in diabetic rats and mice. However, reports on metabolic actions of vanadium in the liver are still contradictory. Thus, the acute effect of sodium orthovanadate infusion on net glucose production was measured in isolated perfused livers of non-fasting, non-diabetic rats. Continuous infusion (0.2 ml/min; 90 min) of vanadate (10–500 mol/l) rapidly increased hepatic glucose (p<0.001), but not cyclic AMP output, reaching peak values after 20 min. The cumulative glucose release displayed concentration dependence with a maximal net effect of 394.3 mol/100 g body weight and an apparent half-maximal effective vanadate concentration of 19.6 mol/l. The glycogenolytic response to vanadate was almost completely blocked by 100 mU/l insulin (p<0.005), by 0.1 mmol/l indomethacin (p<0.05) and in the absence of Ca²⁺ (p<0.001). These results indicate that sodium orthovanadate stimulates glycogenolysis in livers of fed, non-diabetic rats by a Ca²⁺-dependent mechanism, which may involve the release of prostaglandins.     

亚硒酸钠对糖尿病肾病大鼠肾脏脂联素和nephrin表达的影响

目的 探讨亚硒酸钠对糖尿病肾病大鼠肾脏脂联素和nephrin表达的影响及其相互间的关系,从而研究亚硒酸钠与脂联素、nephrin在糖尿病肾病中的作用机制.方法 通过链脲佐菌素法加高脂饮食诱导模拟大鼠糖尿病肾病模型,实验设完全空白对照组、糖尿病组、糖尿病药物干预组,药物干预组每日给予亚硒酸钠溶液灌胃,其它组给予等量盐水溶液灌胃.10周后处死大鼠,取血、尿标本测相关生化指标,取肾脏组织分别提取DNA和蛋白质标本,石蜡切片光镜观察病理改变及免疫组化分析蛋白表达定位,实时定量PCR法检测脂联素mRNA表达、RT-PCR法检测nephrin mRNA表达,Western印迹法检测脂联素和nephrin蛋白表达.结果 亚硒酸钠干预组大鼠生化指标较糖尿病组明显改善,光镜下观察亚硒酸钠干预组病理改变较糖尿病组明显减轻.免疫组化分析,亚硒酸钠干预组脂联素蛋白着色较糖尿病组明显增强,且肾小管、肾小球内均有着色;糖尿病组nephrin蛋白表达着色较空白对照组减少,亚硒酸钠干预组较糖尿病组着色明显增多.亚硒酸钠干预组脂联素mRNA和蛋白表达明显高于糖尿病组和正常对照组,差异有统计学意义(均P＜0.05).亚硒酸钠干预组nephrin mRNA和蛋白表达均较糖尿病组明显增加,但仍较空白对照组降低,差异均有统计学意义(P＜0.05).结论 亚硒酸钠能促进大鼠肾脏脂联素和nephrin表达,表明亚硒酸钠、脂联素和nephrin在延缓和防治糖尿病肾病的发生发展中可能起重要作用.     

Postheparin lipolytic activities in Zucker rats fed with sucrose- or cornstarch-rich diets

In order to study the metabolic effect of dietary sucrose or cornstarch on plasma total triglyceride lipase (T-TGL), hepatic triglyceride lipase (H-TGL) and monoglyceride hydrolase (MGH) activities, young male Zucker fatty and lean rats were pair-fed or fed ad libitum for 4 weeks with diets containing 68% carbohydrate as either sucrose or cornstarch. Our results show that ad libitum feeding of fatty rats with both diets produced an intensification of plasma hypertriglyceridemia which was accompanied by high levels of all plasma postheparin lipolytic activities. These diets did not affect the enzyme activities of lean littermates. Pair-feeding the fatties with sucrose-rich diet produced an increase in T-TGL, H-TGL and MGH. If cornstarch was the carbohydrate included in the diet no difference in postheparin lipolytic activities was found between phenotypes.     

亚硒酸钠对人血淋巴细胞合成DNA的影响

微量法培养人外周新鲜全血和 PHA 刺激淋巴细胞转化,用~3H-TdR 参入 DNA 合成观测不同浓度亚硒酸钠对转化淋巴细胞增殖的影响。结果表明,低浓度亚硒酸钠(1.18×10-~7mol)促进细胞的增殖,细胞 DNA 合成比对照组平均增高43.5%,而高浓度亚硒酸钠(1.18×10-~5mol)抑制细胞的增殖,细胞 DNA 合成比对照组平均降低93.3%。本实验除表明不同浓度亚硒酸钠对细胞增殖的上述双相作用外,还用回归作图法求得此双相作用的临界亚硒酸钠浓度为1.0×10-~6mol。     

Effect of sodium selenite and vitamin E treatment in myotonic dystrophy

Fifteen patients with myotonic dystrophy, seven men and eight women, of age range 15-55 years, were treated with sodium selenite and vitamin E for 2 years. The patients were examined using a number of tests to assess muscle force and function at the start of the treatment period and 6, 12 and 24 months thereafter. Myotonia gives an increased relaxation time. The latter was measured in the adductor pollicis. There was a significant decrease in half relaxation time before treatment compared with the values during treatment. In summary, the results indicate that selenium and vitamin E therapy may have an effect on myotonia. The effects of treatment on motor functions were minimal, and overall motor performance was not improved.     

Experience in pair-feeding of rats treated with nitrate or sodium nitrite

A nutritional and toxicological study has been made of rats, using the pair-feeding technique. The animals were fed a diet containing 5% of NO-3 ion or 0.5% of NO-2 ion (in the form of sodium salts). Under these conditions, a decrease was noted in the consumption of solid food which caused a net loss of weight. Besides, nitrates notably increase liquid intake and diuresis while nitrites induce a significant decrease in the protein retention coefficient.     

Effect of sodium selenite on antioxidative enzymes of banana fruitfly

The median and maximum life spans of Zaprionus paravittiger are 43 and 79 days, respectively, for males and 52 and 91 days for females at 24 +/- 2 degrees C. Sodium selenite (SS), an antioxidant, feeding prolongs the median as well as maximum life span of both the sexes. Antioxidative enzymes, catalase and peroxidase showed greater activity during the developmental stages. Females, at most of the age intervals, exhibited greater enzymatic activities as compared to their age-matched males. Both the sexes showed a statistically significant increase in the baseline activity of these enzymes as consequent upon SS feeding. It is suggested that SS acts by strengthening the antioxidative enzymes, namely catalase and peroxidase.     

亚硒酸钠作用的树突状细胞体外抗乙型肝炎病毒效应

目的:探讨亚硒酸钠作用的树突状细胞(DCs)体外诱导自体淋巴细胞特异性抗乙型肝炎病毒的效应.方法:从乙型肝炎患者外周单个核细胞(PBMC)中诱导DCs,在DCs成熟前加入营养浓度的亚硒酸钠作用,将成熟后的DCs与自身淋巴细胞体外共培养,3d后收集淋巴细胞,分组(乙肝组,加硒组)加入2.2.15细胞培养液中,分别收集24,48和72h的培养上清,检测其表面抗原(HBsAg)和e抗原的分泌以及其与淋巴细胞共培养产生IFN-γ的含量.结果:经亚硒酸钠作用后的DCs组和正常对照组的DCs与自身淋巴细胞共培养产生IFN-γ的浓度,以及在24,48和72h对2.2.15细胞培养上清中HBeAg分泌的抑制效应明显高于乙肝组(34.22±3.17ng/L,3839±2.43ng/L vs 21.47±2.24ng/L;25.90%±1.85%,23.03%±1.51% vs 18.05%±3.64%;37.26%±5.11%,36.88%±5.92% vs 29.52%±2.63%;38.76%±4.00%,40.76%±5.04% vs 35.59%±3.09%,P<0.05).结论:体外经亚硒酸钠作用后的乙肝患者的DC功能可在一定程度上恢复,增强自身淋巴细胞毒性作用并可提高产生IFN-γ的含量,可有效的起到抗乙肝病毒的效应,为以后基于DC的慢性乙型肝炎的免疫治疗提供新思路.