Serum selenium,glutathione peroxidase,lipids, and human liver microsomal enzyme activity

This study evaluated selenium status in relation to lipid peroxidation, liver microsomal function, and serum lipids in humans. Serum selenium concentration, glutathione peroxidase (GSH-Px) activity, liver microsomal enzyme activity, assessed by plasma antipyrine clearance (AP-CL) rate, and serum lipids were determined in 23 healthy subjects in a double-blind placebo-controlled trial of selenium supplementation. The low selenium concentration (74.0±14.2 μg/L, mean±SD) is attributable to the low selenium content of the diet. Subjects with the lowest selenium levels (n=11) had reduced serum GSH-Px activity, AP-CL rate, high-density lipoprotein cholesterol (HDL-C), and total cholesterol (T-C) as compared with subjects with higher selenium concentrations (n=12). Low AP-CL rates were associated with low HDL-C: T-C ratios. Selenium supplementation, 96 μg/d for 2 wk, increased serum selenium, GSH-Px activity, and the HDL-C: T-C ratio. The results suggest that a low serum selenium level is associated with a decrease in liver microsomal enzyme activity and serum HDL-C and T-C concentrations. Selenium supplementation in subjects with low serum selenium may favorably influence relations between serum lipoproteins connected with the development of atherosclerotic vascular disease.     

Effect of different selenium source (sodium selenite and selenium yeast) on broiler chickens

A feeding experiment was carried out to compare the effects of supplementing a poultry meal-based diet with selenium as sodium selenite or selenium yeast on broiler chickens. Three groups with three replicates of broiler chickens (mean weight 710 ± 5.3 g) were given a basal diet either unsupplemented (control) or supplemented with 0.2 mg Se kg⁻¹ as sodium selenite (trial 1) or selenium yeast (trial 2) respectively, for 21 days. There was significant difference (P<0.05) in Feed Conversion Ratio (FCR) of trials 1 and 2 compared with the control. However, there were no significant differences (P>0.05) in FCR between trials 1 and 2. Final weight, survival rate and Daily Gain (DG) were not affected by the dietary Se source. Chickens fed the basal diet showed lower (P<0.05) selenium content in muscle, kidney, liver and pancreas compared to that fed selenium supplements (trials 1 and 2). Furthermore, trial 2 showed the highest value (P<0.05) among these treatments. However, there was no significant difference (P>0.05) in muscle selenium content of chickens between trials 1 and 2. Glutathione peroxidase (GSH-Px) activities in broiler chickens plasma and liver of all selenium treatment groups (trials 1 and 2) were significantly different (P<0.05) from that of the control. The GSH-Px activity in plasma was higher (P<0.05) in trial 2 compared with trial 1 and the control. However, there was no difference (P>0.05) in hepatic glutathione peroxidase between trials 1 and 2 although the average value of GSH-Px activity in trial 2 presented the trend of increase.     

Influence of selenium deficiency on vital functions in rats

To clarify the relationship between selenium (Se) deficiency and functional disorders, the authors determined the Se concentration, anti-oxidant enzyme activity, and other parameters in rats fed a Se-deficient diet. Rats fed the Se-deficient diet showed a decrease in Se concentration and glutathione peroxidase (GSH-Px) activity in plasma, erythrocytes, heart, liver, and skeletal muscle from the first week after the initiation of the diet, an increase in heart lipid peroxide concentration from the second week, and an increase in liver glutathione S-transferase activity from the fourth week. From the twelfth week, a decrease in the growth rate in the rats fed the Se-deficient diet was observed. In spite of this growth impairment, no changes in electrocardiogram, muscle tone, degree of hemolysis, plasma biochemistry, or hematological values were detected. In summary, the authors found that a reduction of body Se is easily induced, but that the appearance of functional disorders following Se deficiency is difficult to detect in rats.     

Effect of selenium supplementation on platelet selenium,glutathione peroxidase,and aggregation

The selenium content of platelets is extremely high. About half of this selenium originates from irreversible incorporation by bone marrow precursor cells, which satisfy their need for selenium even under conditions of marked selenium deficiency. In order to study the effect of increased dietary selenium supply on the concentration of selenium, glutathione peroxidase (GSH-Px-) activity, and aggregability of platelets, normal healthy subjects were supplemented with 300 μg of selenium as Se-rich yeast/d for 3 mo. No significant effect of Se supplementation on platelet Se and GSH-Px were observed, whereas erythrocytes accumulated Se without reaching saturation. Although platelet aggregability was variable during the period of observation, this was traced back to factors other than selenium, including environmental temperature. This study demonstrates that the selenium concentration of platelets is subject to tight physiological control also at high dietary selenium intakes.     

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.     

Lead effects in the chick during selenium deficiency

1. Growing chicks (Gallus domesticus) were fed a selenium-deficient diet supplemented with 0 or 2000 ppm lead (Pb) and 0 or 0.1 ppm selenium (Se). 2. Selenium addition stimulated growth at 0 but not at 2000 ppm Pb, while Pb depressed growth at both levels of Se. 3. Selenium addition stimulated Se-dependent glutathione peroxidase (GSH-Px) activity in liver, but Pb was without effect on GSH-Px activity. 4. Lead addition increased non-protein sulfhydryl (NPSH) concentrations in liver, kidney and thigh muscle. NPSH levels were not altered by Se. 5. The reported antagonism between Pb and Se does not appear to be mediated through effects on GSH-Px or NPSH metabolism.     

The selenium status of Belgian population groups

The selenium state of 40 elderly Belgian people, residing in geriatric homes, has been evaluated. Data are presented on the selenium (Se) contents of their blood, plasma, and erythrocytes. The activity of glutathione peroxidase (GSH-Px) has been assayed. All data were compared with those obtained for 164 young, working adults as presented in Part I of this study. Plasma selenium levels were significantly lower in the old (73 ng/mL) as compared to the young people (97 ng/mL), but erythrocyte Se levels (200 ng/mL) and GSH-Px activity were significantly higher. The selenium concentration in plasma during infancy has also been estimated. The results reveal a very low Se level during the first months of life, with a gradual increase with age. The results are discussed in the light of literature data.     

Levels and 75Se-labeling of specific proteins as a consequence of dietary selenium concentration in mice and rats

Selenium-labeled proteins (SLP) distinct from glutathione peroxidase (GSH-PX) recently have been purified and partially characterized. Antisera to two SLP, a 56-kDa and a 14-kDa protein, were generated in rabbits and used to examine expression of these proteins as a consequence of dietary selenium concentration (0.02, 0.2, 2.0 ppm) in mice and rats. Additionally, the kinetics of 75Se labeling in plasma, liver, kidney, and mammary gland were examined over a 40-hr time period as a function of dietary selenium concentration. A plasma 57-kDa protein was labeled by 30 min after 75Se injection and reached maximum labeling by 4 hr. The cellular 56-kDa and 14-kDa proteins, as well as GSH-Px, labeled progressively over 40 hr starting between 1 and 4 hr after injection. In general, the 56-kDa and GSH-Px followed similar labeling patterns, whereas the 14-kDa protein was labeled less and was not labeled in discernible quantities until 40 hr. The extent of labeling of all proteins was inversely proportional to the dietary selenium concentration and was probably a reflection of different endogenous selenium body pools. The most important observation was generated by the immunoblot data. The amount of 56-kDa and 14-kDa proteins as detected and measured on immunoblots was not a function of dietary selenium concentration. This result suggests that the synthesis and maintenance of the 56-kDa and 14-kDa proteins are not selenium dependent, a characteristic which distinguishes the two proteins from GSH-Px. The single exception to the above results was the 40% decrease of liver 14-kDa protein concentration in carcinogen-treated rats fed 2.0 ppm of selenium. An organic selenium compound, selenobetaine, did not lead to a decrease under similar conditions. In 15 rat mammary tumors induced by 7,12-dimethylbenzanthracene and analyzed on immunoblots, the SLP-56 was undetected in 5 cases and appeared as two bands (56,000 Da, 50,000 Da) in 10 cases. This latter result raises the possibility that the expression of SLP-56 may be altered in mammary tumors as compared with normal mammary gland.     

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.     

Estrogen status alters tissue distribution and metabolism of selenium in female rats

A reported association between estrogen and selenium status may be important in the regulation of selenium metabolism. In this study, the effect of estrogen status on the metabolism of orally administered (75)Se-selenite and tissue selenium status was investigated. Female Sprague-Dawley rats were bilaterally ovariectomized at 7 weeks of age and implanted with either a placebo pellet (OVX) or pellet containing estradiol (OVX+E2), or were sham operated (Sham). At 12 weeks of age, 60 μCi of (75)Se as selenite was orally administered to OVX and OVX+E2 rats. Blood and organs were collected 1, 3, 6 and 24 h after dosing. Estrogen status was associated with time-dependent differences in distribution of (75)Se in plasma, red blood cell (RBC), liver, heart, kidney, spleen, brain and thymus and incorporation of (75)Se into plasma selenoprotein P (Sepp1) and glutathione peroxidase (GPx). Estrogen treatment also significantly increased selenium concentration and GPx activity in plasma, liver and brain, selenium concentration in RBC and hepatic Sepp1 and GPx1 messenger RNA. These results suggest that estrogen status affects tissue distribution of selenium by modulating Sepp1, as this protein plays a central role in selenium transport.     

Selenium and glutathione levels, and glutathione peroxidase activities in blood components of uremic patients on hemodialysis supplemented with selenium and treated with erythropoietin

Patients with chronic renal failure (CRF) often have reduced concentrations of selenium (Se) and lowered activities of glutathione peroxidase (GSH-Px) in blood components. The kidney is a major source of plasma GSH-Px. We measured Se and glutathione levels in blood components and red cell and plasma GSH-Px activities in 58 uremic patients on regular (3 times a week) hemodialysis (HD). The dialyzed patients were divided in 4 subgroups and were supplemented for 3 months with: 1) placebo (bakers yeast), 2) erythropoietin (EPO; 3 times a week with 2,000 U after each HD session), 3) Se-rich yeast (300 μg 3 times a week after each HD), and 4) Se-rich yeast plus EPO in doses as above. The results were compared with those for 25 healthy subjects. The Se concentrations and GSH-Px activities in the blood components of dialyzed uremic patients were significantly lower compared with the control group. Treatment of the HD patients with placebo and EPO only did not change the parameters studied. The treatment with Se as well as with Se and EPO caused an increase in Se levels and red cell GSH-Px activity. Plasma GSH-Px activity, however, increased only slowly or did not change after treatment with Se and with Se plus EPO. In the group treated with Se plus EPO the element concentration in blood components was higher compared with the group supplemented with Se alone. The weak or absence of response in plasma GSH-Px activity to Se supply indicates that the impaired kidney of uremic HD patients has reduced possibilities to synthesize this enzyme.     

Optimization of selenium status by a single intraperitoneal injection of Se in Se-deficient rat: possible application to burned patient treatment

In order to investigate the efficiency of a single selenium (Se) administration in restoring selenium status, Se and antioxidant enzymes were studied in an animal model of Se depletion. In Se-depleted animals receiving or not a single parenteral administration of Se, plasma, red blood cell (RBC), and tissue Se levels were measured concurrently with glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities. The oxidative stress was assessed by thiobarbituric acid-reactive species (TBARs), total thiol groups, glutathione, and tocopherol measurements. Our study showed that Se depletion with alterations in the antioxidant defense system (Se and GPx activity decreases) led to an increase of lipid peroxidation, a decrease of the plasma vitamin E level, and SOD activation. Sodium selenite injection resulted after 24 h in an optimal plasma Se level and a reactivation of GPx activity. In liver, brain, and kidney, Se levels in injected animals were higher than those in reference animals. However, this single administration of Se failed to decrease free radical damage induced by Se depletion. Therefore, in burned patients who exhibit an altered Se status despite a daily usually restricted Se supplementation, the early administration of a consistent Se amount to improve the GPx activity should be of great interest in preventing the impairment of the antioxidant status.     

Protective role of intraperitoneally administered vitamin E and selenium on the antioxidative defense mechanisms in rats with diabetes induced by streptozotocin

The aim of this work was to determine the protective effects of intraperitoneally administered vitamin E and selenium (as Na₂SeO₃, Se) on the lipid peroxidation as thiobarbituric acid reactive substances (TBARS) and vitamin E levels, glutathione peroxidase (GSH-Px), reduced glutathione (GSH) activities in the plasma, red blood cell (RBC), liver, and muscle of rats with streptozotocin-induced diabetes. Fifty adult male Wistar rats were used and all rats were randomly divided into five groups. The first group was used as a control and the second group as a diabetic control. A placebo was given to first and second groups by injection. The third group was intraperitoneally administered with vitamin E (20 mg over 24 h), the fourth group with Se (0.3 mg over 24 h), and the fifth group with vitamin E and Se combination (COM) (20 mg vitamin E + 0.3 mg Se over 24 h). This administration was done for 25 days and the TBARS, vitamin E, GSH-Px, GSH levels in the plasma, RBC, liver, and muscle samples were determined. The vitamin E level in the plasma and liver was significantly (p < 0.05) higher in the control than in the diabetic control group. Also, the TBARS levels in the RBC, liver, and muscle were significantly (p < 0.05) lower in the control than in the diabetic control group. However, GSH-Px and GSH activities in RBC, liver, and muscle were not statistically different between the control and the diabetic control groups. The vitamin E levels in plasma and liver (p < 0.01 and p < 0.001) and GSH-Px activities (p < 0.01, p < 0.001) in RBC were significantly higher in vitamin E, Se, and COM groups than in both control and diabetic control groups. However, the TBARS levels of RBC, muscle, and liver in vitamin E and Se administered groups were significantly (p < 0.05-p < 0.001, respectively) decreased. These results indicate that intraperitoneally administered vitamin E and Se have significant protective effects on the blood, liver, and muscle against oxidative damage of diabetes. The abstract of this study was presented in Physiological Research 48(Suppl. 1), S99 (1999).     

Serum Glutathione Peroxidase Activity and Blood Selenium in Pigs

Blood serum glutathione peroxidase activity and blood selenium concentration were measured in blood samples from pigs subjected to experimentally induced selenium deficiency and dietary selenium supplementation on graded levels. A highly significant correlation between blood selenium and serum GSH-Px activity in pigs, especially in selenium deficient pigs, was demonstrated. There was also a strong relationship between blood selenium concentration and serum GSH-Px activity in pigs receiving dietary selenium at graded levels. Serum GSH-Px activity exhibited an excellent close-response relationship to dietary selenium. Linear regression analysis showed that the increased serum GSH-Px activity was a function of the dietary selenium concentration. The fitness of serum in monitoring slight changes of the selenium status of pigs with help of the estimation of GSH-Px activity was discussed. The measurement of serum GSH-Px activity seems to provide a useful and rapid means for defining selenium requirements and for identifying selenium deficiency in growing pigs.     

Selenium Concentration and Glutathione Peroxidase (GSH-Px) Activity in Serum of Cows at Different Stages of Lactation

The aim of the study was to evaluate the activity of glutathione peroxidase (GSH-Px) and the concentration of selenium in Holstein-Friesian cows at different stages of lactation. Selenium was determined spectrofluorimetrically and GSH-Px activity using a Sigma CGP1 Glutathione Peroxidase Cellular Activity Assay kit. Mean serum selenium concentration was highest in early-lactation multiparous cows (0.18 μg/ml) and the lowest in dry cows (0.111 μg/ml). In early lactation, serum selenium concentration was significantly (P ≤ 0.01) higher in multiparous cows than in cows from the other groups. Mean GSH-Px activity in the serum of dry cows was over twice lower than in late-lactation cows (P ≤ 0.01) and over four times lower than in first-calving heifers and multiparous cows in early lactation (P ≤ 0.01). The coefficients of Spearman's rank correlation between GSH-Px activity and selenium concentration in the cows at different stages of lactation were not significant. A significant (P ≤ 0.01) mean positive correlation (0.46) was found between GSH-Px activity and serum selenium concentration for all the cows analysed together. The highest Se concentration and GSH-Px activity found in the serum of cows during the first stage of lactation may suggest that the generation of reactive oxygen species and their derivatives was higher during this period compared to the other stages, thus placing the cows at a greater risk of oxidative stress. It is therefore essential to give particular attention during this period to meeting the cows' requirement for selenium and other feed components that increase, directly or indirectly, the capacity of the body's antioxidant system.     

Effect of selenium supplementation on some blood biochemical parameters in male rats

The long-term effect of selenium supplementation on blood glutathione peroxidase (GSH-Px) activity and plasma TBARS’ production (as an index of peroxidation) was evaluated in 15-mo-old male rats fed a diet supplemented with 0.25 or 0.50 ppm selenium, for 12 mo. A group of nonsupplemented age-matched rats was the control. In addition, triglycerides, phospholipids, total and free cholesterol, HDL-cholesterol, and HDL-phospholipid levels were measured in plasma. Plasma testosterone levels were also determined in order to control the aging process in these animals. The GSH-Px activity and the peroxidation level were unchanged in all the groups. However, concerning the lipid parameters, a decrease in triglycerides concentration was observed in both treated groups (p<0.05). Therefore, in these experimental conditions, despite no observed changes in parameters related to lipid peroxidation, selenium seems to be involved with triglycerides metabolism, eventually improving the triglycerides status of aged animals.     

The effect of age and selenium on some biochemical parameters in rat liver

Two age groups, 3 and 15 mo, were used to investigate whether age-associated changes in some parameters related to lipid peroxidation occur in the liver of male Wistar rats and to observe possible effects of dietary selenium supplementation (0.25 and 0.50 ppm) for 12 mo on the same parameters. At these experimental conditions, the most important observation was that peroxidation did not change by aging, at least until 15 mo of age. In addition, the activity of Sedependent glutathione peroxidase (GSH-Px, EC 1.11.1.9) was higher in the liver of the older animals. It is suggested that the enzyme could have a role in the unchanged hepatic peroxidation observed in aged male rats. On the other hand, an effect of dietary selenium supplementation on those parameters was not observed, probably because the selenium levels were still at an adequate plateau.     

Changes in ornithine decarboxylase activity and polyamine levels in response to eight different forms of selenium.

The biological activity of selenium is known to depend on its chemical form. In this study, eight forms of selenium that differed in oxidation state or degree of methylation were studied for their acute effects on the activities of ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMet DC) and on the concentrations of the polyamines putrescine, spermidine, and spermine in the liver. The polyamine pathway was studied because it is involved in the control of cell growth and in the cell's response to trophic, carcinogenic, and toxic stimuli, activities that selenium has been reported to affect. Female Sprague Dawley rats were administered 12 mumol Se/kg body weight via intraperitoneal injection and were sacrificed six hours later. Injection of sodium selenate, sodium selenite, selenomethionine, Se-methylselenocysteine, selenobetaine, and selenobetaine methyl ester resulted in significant increases in liver selenium, whereas injection of dimethylselenoxide and trimethylselenonium chloride did not. ODC activity and AdoMet DC activity were induced by those selenium compounds that also increased liver selenium content, but the magnitude of enzyme induction by those compounds was not correlated with the hepatic concentration of total selenium determined fluorometrically. Furthermore, the induction of ODC activity by the various forms of selenium did not result in concomitant increases in putrescine, spermidine, and spermine except in the case of selenite. Given that alterations in the metabolism of selenium are induced when the level of tissue selenium is elevated and that the relative abundance of various selenometabolites can be affected by the point of entry of selenium into intermediary metabolism, these data suggest that the changes that were observed in enzyme activities and polyamine levels are likely to be associated with the accumulation of a specific metabolite of selenium. The relevance of these findings to elucidation of the biological activities attributable to various forms of selenium is under investigation.     

Effect of selenium on the system of superoxide anion radical formation and detoxication in hepatocarcinogenesis

It is established that the introduction of selenium in combination with diethylnitrosamine into rat organisms has a preventive influence on the tumour formation. The intensity of superoxide radicals formation by the liver cell microsomes in this case decreases, while the activity of superoxide dismutase, glutathione peroxidase I, glutathione reductase and concentration of selenium in microsomes increases. The anticarcinogenic action of selenium is considered as a result of an increase in the activity of superoxide dismutase, glutathione peroxidase I and glutathione reductase. This increase induces detoxication of superoxide radicals forming in considerable amounts in rat liver cells under the effect of carcinogen.