Effects of various dietary levels of selenium as selenite or selenomethionine on tissue selenium levels and glutathione peroxidase activity in rats

Weanling rats were fed a basal diet or this diet plus 0.2, 1.0, 2.0 or 4.0 mg/kg selenium (Se) as either selenite or selenomethionine (SeM). Except at the 0.2 mg/kg Se level, Se accumulated in all tissues at higher levels when SeM was fed than when selenite was given, and the magnitude of difference became more pronounced with increasing levels of dietary Se. This was particularly true for muscle and brain. Se levels in whole blood, testes, kidney and lungs were not significantly different between rats fed 0.2 mg/kg Se as selenite or as SeM, but the Se levels in liver, muscle and brain were higher in rats fed SeM. Although the tissue Se concentrations differed markedly, there were no differences in the glutathione peroxidase (GPX) activity in tissues of rats fed SeM rather than selenite. The percentage of Se associated with GPX was lower in all tissues from rats fed SeM than in those from rats fed selenite. These results indicate that the chemical forms of dietary Se can have a marked influence on biological responses, including bioavailability of dietary Se.     

Effect of dietary methionine on utilization of tissue selenium from dietary selenomethionine for glutathione peroxidase in the rat

To study the effect of dietary methionine on the bioavailability of Se from selenomethionine ([Se]Met), weanling rats were first loaded with Se by feeding 0.5 mg Se as [Se]Met per kg diet of a low methionine (0.17% by analysis) torula yeast-based diet for 21 d, and then were fed an Se-deficient diet (less than 0.02 mg Se/kg) supplemented with 0, 0.4 or 0.9% methionine for 28 d. Plasma, liver and muscle Se increased 2.6-, 2.5- and 2.2-fold, respectively, during [Se]Met supplementation, and then the tissue Se declined exponentially during the Se-deficient diet period. Plasma, liver and muscle glutathione peroxidase (GSH-Px) activities decreased 43-50% during the [Se]Met supplementation period in spite of the increase in tissue Se. When these [Se]Met-loaded rats were fed the Se-deficient diet and supplemented with methionine, tissue GSH-Px activities increased significantly within 3 to 7 d, but then decreased for the remainder of the experiment. Calculation of the percentage of tissue Se present as Se in GSH-Px indicated that substantial Se from dietary [Se]Met was stored in tissues in a form different from GSH-Px when a low methionine diet was fed. These results indicate that the dietary methionine level can modulate the availability of Se from dietary [Se]Met and from stored tissue [Se]Met; the inability of stored [Se]Met to provide Se for GSH-Px synthesis over a prolonged period of time suggests that [Se]Met may not be an optimum form for Se supplementation.     

Chemical forms of selenium in rat tissues after administration of selenite or selenomethionine

The chemical forms of selenium (Se) were determined in erythrocyte and liver proteins after injection of 75Se as either sodium selenite or selenomethionine (Se-Met) in male weanling rats. Gel-filtration chromatography (Sephadex G-150) of erythrocyte lysate revealed labeling of four fractions corresponding to void volume proteins, glutathione peroxidase (GPx), hemoglobin (Hb) and low-molecular-weight materials. Acid hydrolysates of erythrocyte protein fractions and whole liver were analyzed by ion-exchange chromatography (Dionex DC6A). Void volume proteins contained principally selenocysteine (75Se-Cys) in [75Se]selenite-injected animals. This material contained both 75Se-Met and 75Se-Cys 1 d postinjection in 75Se-Met-injected animals, but primarily 75Se-Cys at 20 d afterwards. GPx contained 75Se as 75Se-Cys regardless of the selenium compound injected. Hb of 75Se-Met-injected animals contained principally 75Se-Met at both 1 and 20 d postinjection. In [75Se]selenite-injected animals, 75Se was present in hemoglobin as two unidentified forms. In acid hydrolysates of whole liver 75Se was recovered principally as 75Se-Cys from animals injected with [75Se]selenite. For animals injected with 75Se-Met, liver 75Se was present initially as 75Se-Met, but after 5 d the majority of liver 75Se was as Se-Cys. No differences were found in deposition of 75Se in liver, kidney, testes, erythrocytes or plasma in rats injected with labeled selenite or Se-Met, but a significantly greater retention was found in muscle of Se-Met-injected rats as compared to those given selenite.     

不同硒水平饲料对大鼠肝脏谷胱甘肽过氧化物酶和脱碘酶活性的影响

为了解不同饲料硒水平对大鼠肝脏中谷胱甘肽过氧化物酶和脱碘酶活性的影响及确定它们发挥最佳活性时的最低饲料硒水平。５４只体重为５０～６０ｇ的雄性断孔Ｗｉｓｔａｒ大鼠分成９组，分别喂以９种含硒水平为０．０１，０．０２，０．０３，０．０４，０．０５，０．０６，０．１，０．２和５ｍｇ／ｋｇ的不同饲料。实验持续２０周。９组动物２０周的体重增长除５ｍｇ／ｋｇ饲料组与０．１、０．２ｍｇ／ｋｇ饲料组之间有差异外，其余均没有显著性差异。谷胱甘肽过氧化物酶的活性随着饲料硒水平的升高而升高，当饲料硒含量为０．１，０．２和５ｍｇ／ｋｇ饲料时，活性达到最高。因此它发挥正常活性范围的最低饲料硒需要量为０．１ｍｇ／ｋｇ。９个组脱碘酶的活性（ｎｍｏｌ／ｍｉｎ．ｇ）在０．０５至０．２ｍｇ／ｋｇ饲料时活性最高，在５ｍｇ／ｋｇ饲料时酶活性降低，发挥最佳活性最低饲料硒需要量为０．０５ｍｇ／ｋｇ。     

Vitamin B6 dependence of selenomethionine and selenite utilization for glutathione peroxidase in the rat.

The biological availability of selenium from sodium selenite and selenomethionine for glutathione peroxidase activity was studied. Rats were fed ad libitum for 2 weeks a basal diet deficient in both selenium and vitamin B6, and then for the subsequent 2 weeks the same diet supplemented with vitamin B6 (2.5 micrograms as pyridoxine-HCl/g diet) or selenium (2 microgram/g diet) or both. In the presence of vitamin B6, selenite and selenomethionine increased equally the glutathione peroxidase activity in both the liver and erythrocytes above that of selenium-unsupplemented controls. In the absence of vitamin B6, selenomethionine was less effective in the liver and ineffective in the erythrocytes while selenite was equally effective in both tissues and was as effective as in the presence of vitamin B6. These results indicate that selenite selenium is readily available for glutathione peroxidase induction as compared with selenomethionine, and establish that vitamin B6 is involved in the metabolism of selenomethionine to supply selenium for glutathione peroxidase.     

Effect of dietary methionine on tissue selenium and glutathione peroxidase (EC 1.11.1.9) activity in rats given selenomethionine

1. The effect of dietary methionine on the utilization of selenium from dietary selenomethionine [( Se]Met) for tissue Se deposition and for glutathione peroxidase (EC 1.11.1.9; GSH-Px) synthesis was studied in male weanling rats. 2. When rats were given 0.5 mg Se as [Se]Met/kg diet supplemented with 0, 4 or 9 g methionine/kg, Se in plasma, erythrocytes, liver and muscle increased significantly over the 20 d period for all methionine-treatment groups. The increases in erythrocyte and muscle Se, however, were significantly higher in rats fed on the methionine-deficient diet compared with the methionine-supplemented diets. 3. In contrast to the increases in tissue Se, GSH-Px activity in liver, plasma and muscle decreased in methionine-deficient rats given 0.5 mg Se as [Se]Met/kg whereas GSH-Px activity was maintained or increased in rats supplemented with methionine. 4. The percentage of tissue Se associated with GSH-Px was calculated from the measured Se concentration and GSH-Px activity. A significantly lower percentage of Se was associated with GSH-Px in methionine-deficient rats compared with methionine-supplemented rats. 5. These results show that Se from dietary [Se]Met is preferentially incorporated into body proteins rather than used for GSH-Px synthesis when methionine is limiting in the diet. 6. These results further suggest that [Se]Met might not be the optimum Se compound to use for Se supplementation because metabolism of dietary [Se]Met to a biochemically active form, such as GSH-Px, was impaired when [Se]Met was provided in diets low in methionine.     

Effects of dietary zinc and cadmium on tissue selenium concentration and glutathione peroxidase activity in rats fed DL-selenomethionine or sodium selenite.

The effects of dietary zinc (Zn) and cadmium (Cd) on tissue selenium (Se) concentration and glutathione peroxidase (GSH-Px) activity were studied in weanling male Wistar rats. One group of rats was fed a purified diet based on casein and sucrose, and the other rats used in a 2 x 2 x 2 factorial arrangement of treatment were fed this diet supplemented with 0.1 mg Se/kg, either as DL-selenomethionine or sodium selenite and plus 100 mg Zn/kg as zinc sulfate or 5 mg Cd/kg as cadmium chloride or both for 4 weeks. Se concentrations in plasma, erythrocytes, muscle, heart, and liver were significantly elevated by Zn. Cd significantly decreased Se concentration in muscle. Addition of Zn to the diets markedly increased (p less than 0.001) hepatic GSH-Px activity. However, Cd in the diets produced a significant increase (p less than 0.001) in erythrocyte GSH-Px activity. These results indicate that Zn level of marginal deficiency (8.6 mg/kg diet) can decrease Se availability and a small excess of Zn increases Se availability for hepatic GSH-Px activity.     

Effect of dietary selenium on plasma selenoprotein P, selenoprotein P1 and glutathione peroxidase in the rat

The purpose of this study was to determine the effect of dietary selenium on the abundance of selenium in plasma selenoprotein P, selenoprotein P1 and glutathione peroxidase. Weanling rats were provided water that contained 1.0, 0.1 or 0.01 ppm selenium and 75Se for 21 days. Gel filtration of denatured subunits was used to identify 75Se in the selenoproteins. Rats provided 1.0 ppm selenium accumulated 1.5 times more 75Se in liver cytosolic selenoprotein P1, but not in the two other selenoproteins, than did rats provided 0.1 ppm selenium. Most of the liver and blood selenium in rats provided 1.0 ppm selenium was insoluble and in an unknown chemical form. The tissue accumulation of unrecoverable selenium was apparently a response to the high dietary level of selenium. The proportion of selenium in plasma selenoprotein P, a putative selenium-transport protein, reflected the long-term selenium status of rats and varied from approximately 11-58% depending on the level of selenium supplementation. Turnover of selenium from this protein was affected by the dietary selenium of the rats. The results indicate that selenium incorporation into plasma selenoprotein P and selenoprotein P1 is affected by diet in ways that may reflect their importance to the rat.     

Distribution of selenium and glutathione peroxidase in the rat

The selenium content was determined in the adrenals, brain, erythrocytes, femur, hair, heart, kidneys, lungs, muscle, pancreas, plasma, spleen, testes, and thymus of rats, which had been fed a commercial rat diet containing 0.3 mg Se/kg diet. In the plasma, the erythrocytes, and the soluble fraction of the tissues (with the exception of femur and hair) the activity of the glutathione peroxidase (GSH-Px) was measured, using both hydrogen peroxide and t-butyl hydroperoxide as substrates. From the masses of the tissues and the values for the selenium content and the GSH-Px activity, the distribution of the element and the enzyme in the body was calculated. For selenium the main pools were the muscle and the liver, and for the GSH-Px, the liver and the erythrocytes. By comparing the selenium content and the GSH-Px activity the percentage of the tissue selenium, which was bound to the enzyme in the soluble tissue fraction, was estimated. This percentage differed considerably from tissue to tissue, the highest value being found in the erythrocytes and the smallest in the testes. According to this estimation the majority of the selenium in the rat is not contained in the GSH-Px but in other compounds.     

有机硒对谷胱甘肽过氧化物酶活性的影响——随机对照研究的Meta分析

目的探讨补充有机硒对谷胱甘肽过氧化物酶(GPx)活性的影响。方法检索1988年1月-2010年12月发表的观察成人补充有机硒和GPx活性的随机对照研究,Meta分析计算合并标准化均数差(SMD)及95%CI。结果 10篇文献纳入本次研究,观察补硒后血浆GPx的文献为8篇,观察补硒后红细胞、血小板GPx的文献各5篇。和对照组比较,补硒与血浆、红细胞、血小板GPx活性的SMD分别为0.46(95%CI 0.09-0.83)、0.36(95%CI 0.02-0.69)和0.56(95%CI-0.02-1.15)。结论补充有机硒可以提高正常成年人群GPx活性。     

Effect of selenium repletion on glutathione peroxidase protein level in rat liver

We have previously reported that liver glutathione peroxidase (GSH-Px, EC 1.11.1.9) protein level and activity decrease exponentially during Se deficiency. To determine the effect of Se repletion on these parameters, Se-deficient rats were repleted with 0.1 or 0.5 mg Se/kg diet as Na2SeO3 in a 30% torula yeast-based diet and were killed 0, 1, 2, 3, 5, 7 or 14 d later. GSH-Px protein was quantitated using anti-GSH-Px antibodies. Dietary repletion with 0.5 mg Se/kg diet increased GSH-Px protein and activity significantly (P less than 0.05) after 1 d. After 5 d for GSH-Px protein and 7 d for activity the rate of increase slowed, and at d 14 neither GSH-Px protein nor activity was significantly different from that of Se-adequate rats. Repletion with 0.1 mg Se/kg diet did not significantly increase GSH-Px protein or activity until 14 d. To examine the short-term effect of Se repletion, Se-deficient rats were injected intravenously with 15 or 60 micrograms Se as Na2SeO3 and killed 1, 3, 6, 12 or 24 h later. Only rats injected with 60 micrograms Se and killed 24 h later had a significant increase in GSH-Px activity along with a marginally significant increase in GSH-Px protein. These response curves indicate that homeostatic processes control the level of GSH-Px. The lack of an increase in GSH-Px until 24 h after Se administration implies that additional metabolic events after a rise in cellular Se may be necessary prior to an increase in GSH-Px synthesis in Se-deficient rats.     

A human model of selenium that integrates metabolism from selenite and selenomethionine

Selenium (Se) metabolism is affected by its chemical form in foods and by its incorporation (specific vs. nonspecific) into multiple proteins. Modeling Se kinetics may clarify the impact of form on metabolism. Although the kinetics of Se forms have been compared in different participants, or the same participants at different times, direct comparisons of their respective metabolism in the same participants have not been made. The aim of this study was to simultaneously compare kinetics of absorbed Se from inorganic selenite (Sel) and organic selenomethionine (SeMet) in healthy participants (n = 31). After oral administration of stable isotopic tracers of each form, urine and feces were collected for 12 d and blood was sampled over 4 mo. Tracer enrichment was determined by isotope-dilution-GC-MS. Using WinSAAM, a compartmental model was fitted to the data. Within 30 min of ingestion, Se from both forms entered a common pool, and metabolism was similar for several days before diverging. Slowly turning-over pools were required in tissues and plasma for Se derived from SeMet to account for its 3-times-higher incorporation into RBC compared with Se from Sel; these presumably represent nonspecific incorporation of SeMet into proteins. Pool sizes and transport rates were determined and compared by form and gender. The final model consisted of 11 plasma pools, 2 pools and a delay in RBC, and extravascular pools for recycling of Se back into plasma. This model will be used to evaluate changes in Se metabolism following long-term (2 y) Se supplementation.     

Selenium metabolism and platelet glutathione peroxidase activity in healthy Finnish men: effects of selenium yeast, selenite, and selenate

The mean dietary selenium intake in Finland increased from 40 to 100 micrograms/d in 1987 because of the addition in 1985 of selenium to fertilizers. A selenium-supplementation study was performed in 1987 on the same men as were followed in a 1981 study that had a similar design (200 micrograms Se/d). Selenite and selenate, but not selenium yeast increased platelet glutathione peroxidase (GSHPx) activity by 30% compared with placebo, much less than the 70% found in the previous study. Selenium yeast and selenite increased plasma selenium after 11 wk from 1.39 mumol/L to peak values of 2.15 and 1.58 mumol/L, respectively. Only yeast selenium was incorporated into red cells. From a regression plot based on present and literature data, it was estimated that the plasma selenium concentration needed to achieve maximal platelet GSHPx activity was 1.25-1.45 mumol/L. At the present selenium intake in Finland, 100 micrograms/d, GSHPx activity is saturated in plasma and red cells and almost saturated in platelets.     

Influence of dietary peroxides, selenium and vitamin E on glutathione peroxidase of the gastrointestinal tract.

The influence of dietary peroxides, vitamin E and selenium on glutathione peroxidase (GSH-Px) activity in the gastrointestinal tract of the rat was investigated. Feeding 7% oxidized stripped corn oid (peroxide value 1,000) in a diet adequate in selenium and vitamin E increased the specific activity of GSH-Px in the stomach mucosa. Feeding oxidized oil produced an increase in the wet weight of the intestinal mucosa which was associated with a decrease in the specific activity of the enzyme. Total GSH-Px activity in the intestinal mucosa was unchanged or moderately increased. These changes were unaffected by the presence of vitamin E in the diet. Dietary peroxides had no effect on GSH-Px activity in the plasma or in the perirenal and paraepididymal adipose tissues. Subacute vitamin E deficiency had no consistent effect on the activity of the enzyme in several tissues examined. In rats fed a Se deficient diet glutathione peroxidase activity decreased markedly in most tissues but only slightly in the intestinal mucosa. The moderate decrease in the intestine may be explained by the accessibility of residual dietary Se to the mucosal cells. The role of Se in the detoxification of peroxides in foods and the response of gastrointestinal GSH-Px to dietary peroxides are discussed.