Selenium and Glutathione Peroxidase Levels in Lambs Receiving Feed Supplemented with Sodium Selenite or Selenomethionine

Twenty-one 6 months old female lambs were divided into 7 groups and fed a basal diet containing 0.13 mg Se/kg. The basal diet was further supplemented with 0, 0.1, 0.5 or 1.0 mg Se/kg either as sodium selenite or as selenomethionine, and was fed for 10 weeks. Both feed additives produced an increase in the selenium concentration in the tissues analysed. Significant correlations were found between the concentrations of selenomethionine or sodium selenite added to the feed and the subsequent tissue levels. However, the selenium levels seemed to plateau at approximately 0.5 mg Se/kg of supplemented sodium selenite. The total glutathione peroxidase (GSH-Px) activity of the tissues increased when the selenium supplementation increased from 0 to 0.1 mg/kg for both selenium compounds. With further increase in selenium supplementation the GSH-Px activity in the tissues plateaued except in the blood where the activity continued to rise with increasing selenomethionine supplementation. The selenium dependent GSH-Px activity in the liver rose with increasing selenomethionine supplementation, but approached a plateau when 0.1 mg Se/kg as sodium selenite was added to the feed. The selenium concentration in whole blood responded more rapidly to the selenium supplementation than did GSH-Px activity. The experiment indicates that the optimal selenium concentration in the feed is considerably higher than 0.1 mg Se/kg, and that selenium levels of 1.0 mg/kg in the feed do not result in any risk for the animals or the consumers of the products.     

Effects of long-term selenium deficiency on glutathione peroxidase and thioredoxin reductase activities and expressions in rat aorta

The objective of this work was to determine whether long-term selenium (Se) deficiency might affect the antioxidant capacity of rat aorta, and the activities and expressions of glutathione peroxidase (GPx) and thioredoxin reductase (TR) in rat arterial walls. Weanling male Wister rats were fed Se-deficient or Se-adequate diets for 12 months. For the Se supplementation, sodium selenite was supplemented in drinking water (1 microg Se/ml) for 1 month. The aorta isolated from these groups were used to determine activities and mRNA levels. In comparison with the control, the activity and expression of GPx, superoxide dismutase activity and the total antioxidant capacity were significantly decreased in Se-deficient rats arterial walls. Following Se supplementation, they were restored to different extents. The content of malondialdehyde was increased markedly in Se-deficient rats. There seems an inverse relationship between the dietary Se and the activity and expression of TR. A positive relationship exists between dietary Se and the antioxidant capacity of rat arterial walls. The activities and expressions of GPx and TR in arterial walls were regulated by selenium by different mechanisms. Regulation of the expression of TR was mediated by reactive oxygen species, but of GPx by selenium status. The thioredoxin system may be the major cellular redox signaling system in rat arteries, rather than the glutathione system.     

Biological effects of a nano red elemental selenium.

A novel selenium form, nano red elemental selenium (Nano-Se) was prepared by adding bovine serum albumin to the redox system of selenite and glutathione. Nano-Se has a 7-fold lower acute toxicity than sodium selenite in mice (LD(50) 113 and 15 mg Se/kg body weight respectively). In Se-deficient rat, both Nano-Se and selenite can increase tissue selenium and GPx activity. The biological activities of Nano-Se and selenite were compared in terms of cell proliferation, enzyme induction and protection against free racial-mediated damage in human hepatoma HepG2 cells. Nano-Se and selenite are similarly cell growth inhibited and stimulated synthesis of glutathione peroxidase (GPx), phospholipid hydroperoxide glutathione peroxidase (PHGPx) and thioredoxin reductase (TR). When HepG2 cells were co-treated with selenium and glutathione, Nano-Se showed less pro-oxidative effects than selenite, as measured by cell growth. These results demonstrate that Nano-Se has a similar bioavailability in the rat and antioxidant effects on cells.     

Effects of different selenium sources on tissue selenium concentrations,blood GSH-Px activities and plasma interleukin levels in finishing lambs

Thirty-two wether lambs of Tan sheep were randomly assigned into four dietary treatment groups (eight per group) for an 8-wk study and then fed a basal diet deficient in Se (0.06 mg/kg) or diets supplemented to provide 0.10 mg/kg Se from sodium selenite, selenized yeast, and selenium-enriched probiotics, respectively. Blood samples were collected at d 0, 28, and 56 of the experiment and tissue samples were collected at experiment termination. Tissue and blood Se concentrations, blood glutathione peroxidase (GSH-Px) activities, and plasma interleukin levels were analyzed. The results showed that the concentrations of Se in the kidney, liver, and muscle increased in all of the supplemented groups (p<0.01) compared with the control group. However, the Se concentrations in the kidney, liver, and muscle in the groups supplemented with Se yeast and Se-enriched probiotics were higher than those in the group supplemented with sodium selenite (p<0.01). The activities of GSH-Px and the concentrations of Se in blood also increased in all of the supplemented groups during the period of supplementation (p<0.01) compared with the control group. The activities of GSH-Px and the concentrations of Se in the whole blood of the lambs fed with selenized yeast and Se-enriched probiotics were higher than those of lambs fed with sodium selenite (p<0.01 or p<0.05). The concentrations of interleukin-1 and interleukin-2 in plasma significantly increased in all of the supplemented groups during the entire period of experiment (p<0.01) compared with the control group, but had no significant differences among all of the supplemented groups. In conclusion, a diet supplemented with Se for finishing lambs was able to increase the concentrations of Se in tissue and blood, activities of GSH-Px in blood, and levels of interleukins in plasma. Organic Se sources (selenized yeast and Se-enriched probiotics) were more effective than the inorganic Se source (sodium selenite) in increasing tissue and blood Se concentrations and blood GSH-Px activities of lambs. However, there were no significant differences in plasma interleukin levels of lambs between organic and inorganic Se sources.     

The Influence of Selenium on Root Growth and Oxidative Stress Induced by Lead in Vicia faba L. minor Plants

The effect of selenium (Se) on Vicia faba L. minor roots subjected to lead (Pb) stress was studied by investigating root growth, root viability, and antioxidant enzyme activity. The experiments were carried out on plants grown for 2 weeks on Hoagland medium supplied with 50 μM Pb in the form of lead nitrate Pb(NO(3))(2) and/or Se concentrations of 1.5 and 6 μM in the form of sodium selenite Na(2)SeO(3). It was shown that Pb reduced the root growth and caused serious damage in the roots, which was accompanied by metal accumulation in these tissues. The exposition of roots to Pb led to significant changes in the biochemical parameters: the MDA and T-SH content and glutathione peroxidase (GSH-Px) activity increased but the guaiacol peroxidase (GPOX) activity decreased. Moreover, Pb intensified O(2)(·-) production in the roots. Selenium at a lower concentration alleviated Pb toxicity which was accompanied by a decreased O(2)(·-) production in the apical parts of roots and increased the T-SH content and GPOX activity. However, higher Se concentration intensified MDA and T-SH accumulation and GPOX and GSH-Px activity in Pb-treated plant roots. At low concentration, Se improved cell viability whereas at high concentration it was pro-oxidant and enhanced the lipid peroxidation and cell membrane injury.     

Selenium modifies glutathione peroxidase activity and glutathione concentration in mice exposed to ozone-provoked oxidative stress

The aim of this study was to show the direct effect of selenium on glutathione peroxidase (GSH-Px) activity and GSH/GSSG concentrations in 3- and 6-month-old mice. An ozone-oxygen mixture was used to provoke an oxygen stress. To measure the Se-effect mice were gavaged with sodium selenite. GSH-Px activity and total glutathione concentrations were determined in serum and in the postnuclear fraction of liver and lungs. Additionally glutathione concentrations were determined in whole blood. Both ozone and selenium, administered separately, reduced GSH-Px activity in lungs of 6-month-old animals, while in young mice an opposite effect of Se was observed. Ozone administered jointly with Se did not influence GSH-Px activity in 6-month-old mice, while in young, 3-month-old mice, a stimulatory effect in lungs was observed. There were no significant changes in GSH-Px activity in the liver of 6-month-old mice, but the stimulatory effect occurred in young mice treated with Se and Se & ozone jointly. In young mice, ozone (also ozone with Se) augmented glutathione concentrations. The response to ozone and selenium strictly depended on age and the antagonism between selenium and ozone was observed only in a few cases.     

Effect of Organic Selenium Supplementation on Selenium Status,Oxidative Stress,and Antioxidant Status in Selenium-Adequate Dairy Cows During the Periparturient Period

The periparturient period represents a stressful time for dairy cows as they transition from late gestation to early lactation. Oxidation stress occurs during this period owing to the increased metabolic activity. Antioxidants supplementation slightly above the suggested requirements may be beneficial in relieving this kind of stress. The objective of this study was to determine whether supplementing selenium (Se) yeast to diets with adequate Se concentrations affects Se status, oxidative stress, and antioxidant status in dairy cows during the periparturient period. Twenty multiparous Holstein cows were randomly divided into two groups with ten replicates in each group. During the last 4 weeks before calving, cows were fed Se-yeast at 0 (control) or 0.3 mg Se/kg dry matter (Se-yeast supplementation), in addition to Na selenite at 0.3 mg Se/kg dry matter in their rations. The concentrations of Se, reactive oxygen species (ROS), hydrogen peroxide (H₂O₂), hydroxyl radical, malonaldehyde (MDA), α-tocopherol and glutathione (GSH), the activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT), and the total antioxidant capacity (T-AOC) in plasma or erythrocyte of dairy cows were measured at 21 and 7 days prepartum, and at 7 and 21 days postpartum. Cows fed Se-yeast supplement during the last 4 weeks of gestation had higher plasma Se and lower MDA concentrations at 7 days prepartum, and at 7 and 21 days postpartum, and had higher whole blood Se and lower plasma ROS and H₂O₂ concentrations at 7 and 21 days postpartum compared with control cows. Se-yeast supplementation increased plasma and erythrocyte GSH-Px activities and erythrocyte GSH concentration at 7 days postpartum as compared to Se-adequate control cows. Compared with control cows, the enhanced SOD and CAT activities, increased α-tocopherol and GSH concentrations, and improved T-AOC in plasma at 7 and 21 days postpartum in Se-yeast-supplemented cows were also observed in this study. The results indicate that feeding Se-adequate cows a Se-yeast supplement during late gestation increases plasma Se status, improves antioxidant function, and relieves effectively oxidative stress occurred in early lactation.     

Effect of dietary fluoride on selenite toxicity in the rat

Three factorial experiments were conducted to determine if high dietary fluoride (F) would inhibit selenite toxicity in rats. Initially, three levels of selenite (0.05, 3, and 5 mg/kg diet) were matched against three levels of F (2, 75, and 150 mg/kg diet). Fluoride failed to prevent the depressive effect of selenite on 8-wk food intake and body wt gain. Selenium (Se) concentration of plasma and kidney and enzymatic activity of whole blood glutathione peroxidase (GSH-Px) were also unaffected by F. Liver Se concentration, however, was slightly (12%) but significantly (p<0.025) reduced when the highest F and Se levels were combined. Fluoride (150 mg/kg) appeared to reduce liver selenite toxicity (5 mg/kg). Therefore, further study focused on liver histology with treatments that eliminated the middle levels of selenite and F. Fluoride prevented the hepatic necrosis seen in selenite-toxic rats. Similar histological lesions were not observed for kidney or heart. Fluoride partially (26%) but significantly (p<0.025) reduced thiobarbituric-reactive substances in selenite-toxic rats, but there was no F effect on intracellular distribution of liver Se, glutathione levels in liver and kidney, or on liver xanthine oxidase activity. Overall, the protective effect of F on selenite toxicity appears to be confined to liver pathology. The exact mechanism for this effect, however, remains unclear. Oregon Agricultural Experiment Station Technical Paper No. 9728.     

Evaluation of nutritional availability and anti-tumor activity of selenium contained in selenium-enriched Kaiware radish sprouts

We estimated the nutritional availability of selenium (Se) in Se-enriched Kaiware radish sprouts (SeRS) by the tissue Se deposition and glutathione peroxidase (GPX) activity of rats administered the sprouts, and examined the effect of SeRS on the formation of aberrant crypt foci (ACF) in the colon of mice administered 1,2-dimethylhydrazine (DMH) to evaluate anti-tumor activity. Male weanling Wistar rats were divided into seven groups and fed a Se-deficient basal diet or the basal diet supplemented with 0.05, 0.10, or 0.15 microg/g of Se as sodium selenite or SeRS for 28 d. Supplementation with Se dose-dependently increased serum and liver Se concentrations and GPX activities, and the selenite-supplemented groups showed a higher increase than the SeRS-supplemented groups. The nutritional availability of Se in SeRS was estimated to be 33 or 64% by slope ratio analysis. Male 4-week-old A/J mice were divided into seven groups and fed a low Se basal diet or the basal diet supplemented with selenite, SeRS, or selenite + non-Se-enriched radish sprouts (NonSeRS) at a level of 0.1 or 2.0 microg Se/g for 9 weeks. After 1 week of feeding, all mice were given six subcutaneous injections of DMH (20 mg/kg) at 1-week intervals. The average number of ACF formed in the colon of mice fed the basal diet was 4.3. At a supplementation level of 0.1 mug Se/g, only SeRS significantly inhibited ACF formation. At a supplementation level of 2.0 microg Se/g, both selenite and SeRS significantly inhibited ACF formation. The addition of NonSeRS to the selenite-supplemented diets tended to inhibit ACF formation, but this was not statistically significant. These results indicate that SeRS shows lower nutritional availability but higher anti-tumor activity than selenite.     

Effects of Selenium and Vitamin E,in Addıtıon to Melatonin,Against Oxidative Stress Caused by Cadmium in Rats

The present study was carried to evaluate the protective effects of melatonin alone and vitamin E with selenium combination against high dose cadmium-induced oxidative stress in rats. The control group received subcutanous physiological saline. The first study group administered cadmium chloride (CdCl₂) by subcutaneous injection of dose of 1 mg/kg. The second study group administered cadmium plus vitamin E with selenium (1 mg/kg sodium selenite with 60 mg/kg vitamin E); the third study group administered cadmium plus 10 mg/kg melatonin (MLT); the fourth study group administered CdCl₂ plus a combination of melatonin in addition to vitamin E and selenium for a month. Determination levels of plasma malondialdehyde (MDA), glutathione peroxidase (GSH-Px), blood superoxide dismutase (SOD), creatinine alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), blood urea nitrogen (BUN), and urea were measured in serum. In only CdCl₂ administered group, the MDA, creatinine, ALT, AST, ALP, and urea levels in the serum were significantly higher than the control group (p < 0.05). Whereas in all other groups, this values were significantly lower than the only CdCl₂ administered group (p < 0.05). Erythrocytes GSH-Px, serum SOD activities of only CdCl₂ received group were significantly lower than the control group (p < 0.05). In conclusion, vitamin E + Se, melatonin and vitamin E, and Se, in addition to MLT combinations, had protective effects against high dose cadmium-induced oxidative damage.     

Effect of selenium supplementation on mice infected with LP-BM5 MuLV, a murine AIDS model

LP-BM5 Murine leukemia virus (MuLV) infection of C57BL/6 mice develop a disease that has many features in common with human acquired immunodeficiency syndrome (AIDS), in particular abnormal lymphoproliferation and severe immunodeficiency. Thus, this MAIDS model may be useful for evaluation of potent antirival agents in vivo. Deficiency in antioxidant micronutients such as selenium, zinc, and glutathione have been observed in AIDs and AIDS-related complex (ARC) patients. In the present study, the MAIDS model was used to evaluate immunological and oxidative effect of Se as sodium selenite. Results indicated that Se treatment 0.1 mg/kg/d (p.o.) inhibited splenomegaly and sera IgG elevation effectively. In addition to abnormal immunity, oxidative imbalance possibly existed in MAIDS model, as lipid peroxide increased significantly in spleen and whole blood glutathione peroxidase (GSH-Px) activity decreased markedly. Se supplementation had good protective effect.     

Comparative Effect of Selenium in Wheat,Barley, Fish Meal and Sodium Selenite for Prevention of Exudative Diathesis in Chicks

Groups af White Leghorn chicks obtained from dams deprived on selenium (Se), were fed from hatching a low-Se-vitamin E basal diet alone, or supplemented with 0.02, 0.04, 0.06 or 0.08 mg Se/kg diet, as sodium selenite (Na2SeO3 · 5H2O), wheat, barley or fish meal. Prevention of the Se-vitamin E deficiency responsive disease exudative diathesis (ED) as it was clinical observed, induction of the plasma Se dependent enzyme glutathione peroxidase (GSH-Px) activity, and Se concentration in the cardiac muscle were observed to be dietary Se level and source dependent. Slope ratio assay was applied to estimate the biological availability of Se in the natural sources relative to Se in sodium selenite. For the prevention of ED, the bioavailability of Se in wheat, barley and fish meal was 99, 85 and 80 %, respectively. The increase in the plasma GSH-Px activity revealed a bioavailability for Se in wheat, barley and fish meal of 79, 71 and 66 %, respectively. Using retention of Se in the cardiac muscle as the bioassay, a bioavailability of 108, 87 and 100 % was calculated for wheat, barley and fish meal Se, respectively.     

Oxidative Stress and Paraoxonase Activity in Experimental Selenosis: Effects of Betaine Administration

The present study was undertaken on male rats to elucidate the selenosis induced by sodium selenite and the role played by betaine in alleviating selenium toxicity. Rats were treated with sodium selenite (6 mg/kg body weight/day) with or without betaine (240 mg/kg body weight/day). Selenotoxicosis was evident from the elevated plasma levels of total bilirubin, transaminases, and alkaline phosphatase activities. Moreover, the total protein levels decreased, and this decrease associated with a decreased albumin level, whereas the globulin level increased in selenium-intoxicated rats. The development of selenosis corresponded well with the induction of oxidative stress evident from decrease of total thiol level and glutathione content. Furthermore, activities of glutathione reductase, glucose-6-phosphate dehydrogenase, catalase, and paraoxonase-1 were decreased in selenium-treated rats. In contrast, superoxide dismutase and glutathione peroxidase activities were increased by excess selenium administration compared with control animals. As well, malondialdehyde and protein carbonyl were elevated in rats treated with selenium. Supplementation of betaine simultaneously with selenium caused less marked alteration in the investigated parameters. Betaine attenuated the selenotoxicosis by restoring thiol levels that preserve enzymatic antioxidants activity and attenuate the oxidation of lipids and proteins.     

Selenium supplementation of children in a selenium-deficient area in China

Keshan disease is a cardiomyopathy restricted to the endemic areas of China and seen in residents having an extremely low selenium (Se) status. Prophylactic administration of sodium selenite has been shown to decrease significantly the incidence of acute and subacute cases. The aim of the study was to assess the relative bioavailability of selenite versus organic Se-yeast in a Se-deficient area in China with a randomized double-blind double-dummy design. Healthy children (n=30) between 14 and 16 yr of age were randomized into three equal groups receiving either 200 μg/d selenite Se or 200 μg/d Se-yeast or placebo for 12 wk. Blood was drawn at baseline, 4, 8, and 12 wk and 4 wk postsupplementation. The plasma Se concentration (mean ± SD) was 0.16±0.03 μmol/L at baseline. Selenite and Se-yeast supplementation increased plasma Se to plateau values, 1.0±0.2 and 1.3±0.2 μmol/L, respectively. In red cells, Se-yeast increased the selenium level sixfold and selenite threefold compared to placebo. The relative bioavailability of Se-yeast versus selenite measured as glutathione peroxidase (GSHPx) activity was similar in plasma, red blood cells, and platelets. GSHPx activity reached maximal levels in plasma and platelets of 300% and 200%, respectively, after 8 wk compared to the placebo group, but continued to increase in red cells for 16 wk. Our study showed that although both forms of Se were equally effective in raising GSHPx activity, Se-yeast provided a longer lasting body pool of Se. Se-yeast may be a better alternative to selenite in the prophylaxis of Keshan disease with respect to building up of body stores.     

Comparative effects of selenite and selenite on the glutathione-related enzymes activity in pig blood platelets

The effects of inorganic selenium (Se) compounds (sodium selenite and selenate) on the activities of glutathione-related enzymes (glutathione peroxidase, glutathione-S-transferase [GST] and glutathione reductase [GR]) in pig blood platelets were investigated in vitro. GST activity in blood platelets treated with 10⁻⁴ M of selenite was reduced to 50%, whereas no decrease GST activity was observed after the treatment of platelets with the same dose of selenate. In platelets incubated with physiological doses (10⁻⁷, and 10⁻⁶ M) of Se compounds, the activity of glutathione peroxidase (GSH-Px) was enhanced (about 20%). GR activity after the exposure of platelets to tested Se compounds was unaffected.     

In vivo and in vitro influence of selenium on DNA/RNA synthesis in spleen and lymphocytes in culture--possible mediation of changes in GSH/GSSG ratio

Effect of superanutritional levels of selenium (Se) as sodium selenite (0.5 and 1.5 ppm) given orally to Balb/c mice for one and two weeks was observed on the rate of DNA/RNA synthesis, levels of reduced as well as oxidized glutathione (GSH and GSSG) and glutathione peroxidase (GSH-Px)/glutathione-S-transferase (GSH-S-transferase) activities in spleen. Similar effect of three different concentrations of Se (10(-7), 10(-5) and 10(-3) M) in culture media was also observed on the rate of DNA/RNA synthesis in proliferating lymphocytes taken from mice spleen. The results of the present study indicated that with increasing concentration and duration of Se treatment in vivo and in vitro, a marked inhibition of the rate of DNA/RNA synthesis was observed. Levels of total glutathione and GSSG in spleen were elevated significantly only after two weeks in 1.5 ppm treatments. Glutathione peroxidase activities in spleen decreased (p < 0.05) in 1.5 ppm group at one week and in 0.5 ppm group at two week treatment. At higher Se treatment, the activity recovered towards control. However, GSH-S-transferase in spleen remained unchanged at all treatment intervals. The results indicated that changes in glutathione system by increasing Se concentration might account for inhibition of rate of DNA/RNA synthesis.     

Effect of 3-(1<Emphasis Type="Italic">H</Emphasis>-Pyrrol-2-yl)-1<Emphasis Type="Italic">H</Emphasis>-Indazole on the Antioxidant Status of Rats

The influence of injection periods of 3-(1H-pyrrol-2-yl)-1H-indazole regarding vitamins A, E, C, selenium (Se), malondialdehyde (MDA) levels, and glutathione peroxidase (GSH-Px) activity in rats has been investigated. The substance was given by subcutaneous injection at 20 mg/kg every other day for a total of 15 injections. At the end of the treatment, Se levels in serum were determined by fluorimetry, and those of vitamins A, E, C, and malondialdehyde in serum, liver, and kidney were determined by high-performance liquid chromatography. GSH-Px activities in erythrocytes were determined spectrophotometrically. Vitamins A, E, C, and Se levels were generally lower than in the controls, while GSH-Px activity at the third injection period was maximally increased, with the activities after the other injection periods being higher than in the control group. In addition, vitamins A, E, and C levels were generally lower than the control groups, while serum, liver, and kidney MDA levels gradually increased depending on injection periods. On the other hand, GSH-Px activity was higher than in the control group. Thus, the results show that while vitamins A, E, C, and Se levels decreased, MDA levels and GSH-Px activities increased after administration of 3-(1H-pyrrol-2-yl)-1H-indazole to the rats. These findings might be related to the increased amount of free radicals caused by 3-(1H-pyrrol-2-yl)-1H-indazole injection.