Glutathione peroxidase activity modulates fatty acid profiles of plasma and breast milk in Chinese women.

Since little is known about the effect of selenium on the fatty acid profiles (FAP) of human breast milk, the purpose of this study was to measure the effect of habitual dietary selenium (Se) intake on this profile in plasma and breast milk. Subjects were lactating women from three locations in China where habitual selenium intakes are extremely low (Xichang), adequate (Beijing), or extremely high (Enshi). Plasma and milk samples were obtained within seven days of parturition (early samples) or within eighteen months postpartum (mature samples) and analyzed for selenium concentration, glutathione peroxidase (Gpx) activity and FAP. Plasma and milk selenium concentrations were significantly lower in the samples from women from Xichang and significantly higher in those from Enshi when compared to those from Beijing. Plasma Gpx activity, however, was higher in samples from Beijing than Xichang or Enshi. In contrast, the early breast milk samples had similar Gpx activity regardless of location. The mature samples, however, followed the same trend as plasma with the samples obtained from the women in Beijing having the highest activity. Of the unsaturated fatty acids examined, the concentration of linoleic acid, 18:2(n-6), in both plasma and milk was greater in the samples from Beijing when compared to those from Xichang or Enshi. Thus dietary selenium appears to influence the fatty acid composition in human breast milk, but influences Gpx activity only in mature milk samples.     

Blood selenium and glutathione peroxidase activity of populations in New Zealand, Oregon, and South Dakota

The relationship of whole blood selenium (Se) to glutathione peroxidase (GPX) activity was examined for individuals in New Zealand, Oregon, and South Dakota who represented, respectively, populations with exposure to low, medium, and high amounts of Se. The mean (respective) blood Se levels were 60, 200, and 400 ng/ml. Intergroup differences in blood Se levels were highly significant (P less than 0.001). GPX assays were performed using two variations of an enzyme-coupled procedure to assess the equivalence of the two methods. Despite a fourfold difference in absolute activities measured by these methods, the GPX activities were highly correlated (r = .86) between procedures. Average blood GPX activity was significantly lower (P less than 0.001) for the New Zealand group compared with the other two groups, but there was no difference in GPX activities between the Oregon and South Dakota groups. Linear regression of GPX vs. Se values within each group indicated a significant correlation of these parameters only in the New Zealand group (r = .46, P less than 0.01). Comparison of these parameters for combined data from all three groups also showed a significant positive correlation (r = .60, P less than 0.001). A saturation model (In GPX = k1 + k2 (Se)-1)) fits the combined data better (r = .80, P less than 0.01) than does direct comparison of the two parameters. These results suggest that GPX activity is an appropriate indicator of human Se status only in populations with below normal exposure to Se, as activity of this enzyme is saturated at relatively low levels.     

Comparison of whole blood selenium values and erythrocyte glutathione peroxidase activities of normal individuals on supplementation with selenate,selenite,l-selenomethionine,and high selenium yeast

The selenium levels and the glutathione peroxidase activity GSH-PX of whole blood and of erythrocytes, respectively, were determined in 139 normal Danes and related to sex and smoking habits. No differences were found in relation to sex apart from a higher GSH-PX activity of females when assayed with tertiary butyl hydroperoxide. Smokers showed significantly lower selenium values than non-smokers (p<0.05), but the two groups had identical GSH-PX activities. Individuals from the above-mentioned group were divided into four groups, receiving daily oral doses of 200 μg of selenium in the form of selenite, selenate, L-selenomethionine, and selenium as contained in yeast. Whole blood selenium values and the erythrocyte glutathione peroxidase activities were determined during three months of supplementation followed by a withdrawal period of four months. Both the inorganic selenium compounds and the organic derivatives gave rise to steady state levels of GSH-PX after one month of supplementation. However, the selenium levels in the groups receiving organic selenium showed a steady rise during the whole period, whereas those supplemented with inorganic selenium leveled off after a period of one to three months. The data for smokers and non-smokers revealed identical results when organic selenium was supplemented. However, selenite gave rise to significantly higher selenium levels and GSH-PX activities in smokers than in non-smokers. Less significant (p<0.08) elevations of both parameters were also observed among the smokers in the selenate group. By taking both the selenium level and the GSH-PX activity into consideration, organic selenium (i.e.,l-(+) selenomethionine) was judged to be more bioavailable than selenite and selenate.     

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.     

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 supplementation on plasma glutathione peroxidase activity in patients with end-stage chronic renal failure

Patients with chronic renal failure (CRF) usually have a lower than healthy level of selenium (Se) in whole blood and plasma. Plasma glutathione peroxidase (GSH-Px) is synthesized mostly in the kidney. In CRF patients, activity of this enzyme is significantly reduced and its reduction increases with the progress of the disease. The aim of the study was to evaluate the effect of Se supplementation to CRF patients at various stages of the disease on Se concentration in blood components and on plasma GSH-Px activity. The study group comprised 53 CRF patients at various stages of the disease supplemented with Se (200 μg/d for 3 mo as Se-enriched yeast, containing about 70% l-selenomethionine [SeMet]). The control group consisted of 20 healthy subjects. The Se concentration in blood components was measured spectrofluorometrically with 2,3-diaminonaphthalene as a complexing reagent. GSH-Px activity in red cell hemolysates and plasma was assayed by the coupled method with tert-butyl hydroperoxide as a substrate. The Se concentration in whole blood and plasma of CRF patients is significantly lower as compared with healthy subjects, but similar at all stages of the disease. In the patients’ plasma, total protein and albumin levels are also significantly lower than in healthy subjects. Plasma GSH-Px activity in patients is extremely low, and contrary to Se concentration, it decreases linearly with the increasing stage of the illness. Se-supplied patients show an increased Se concentration in all blood components and at all disease stages, whereas plasma GSH-Px activity is enhanced only at the incipient stage of the disease. Se supply has no effect on plasma GSH-Px activity in uremic patients at the end stage of the disease. Total plasma protein and albumin levels did not change after Se supplementation. Our data seem to show that in patients with CRF lower total protein and albumin levels in plasma may be the chief cause of the low blood and plasma Se concentrations. GSH-Px activity decreases along with the kidney impairment. At the end stage of the disease, Se supplementation in the form of Se-enriched yeast has no effect on the increase in plasma GSH-Px activity.     

Glutathione peroxidase activity and selenoprotein W levels in different brain regions of selenium-depleted rats(1)

Previous studies in selenium (Se)-depleted sheep and rats showed that selenoprotein W (SeW) levels decreased in all tissues except brain. To further investigate this depletion in different parts of the brain, second generation Se-depleted rats were used. Dams consumed a Se-deficient basal diet during gestation and lactation, and deficient rats were obtained by continuation on the same diet. Control rats were fed a diet with 0.1-mg Se/kg diet after weaning. Glutathione peroxidase (GPX) activities were measured for comparative purposes to SeW levels. GPX activity in muscle, skin, spleen, and testis increased about 4-fold with Se repletion and reached a plateau after 6 or 10 weeks, but GPX activity decreased to almost one tenth of the original activity with continuous Se depletion. In contrast, GPX activities increased, rather than declined, in various brain regions (cortex, cerebellum, and thalamus) with time of feeding the deficient diet. An experiment with first generation rats, however, indicated that GPX activity was significantly lower in these three brain regions from rats fed the deficient diet as compared to rats fed the supplemented diet. SeW levels in skin, spleen, muscle, and testis were undetectable in weanling rats, but became detectable after 6 weeks of Se repletion. In contrast, the expression of SeW in cortex, cerebellum, and thalamus was not significantly affected by Se depletion, but increased SeW levels occurred only in thalamus with Se supplementation. The results with GPX using first and second generation rats suggest that there are "mobile" and "immobile" GPX fractions in the brain.     

Selenium-independent epididymis-restricted glutathione peroxidase 5 protein (GPX5) can back up failing Se-dependent GPXs in mice subjected to selenium deficiency

We have previously characterized and cloned a secreted sperm-bound selenium-independent glutathione peroxidase protein (GPX5), the expression of which was found to be restricted to the mouse caput epididymidis. Because of the lack of selenium (Se) in the active site of this enzyme, unlike the other animal GPXs characterized to date, it was suspected that GPX5 does not function in the epididymis as a true glutathione peroxidase in vivo. In the present report, following dietary selenium deprivation which is known to reduce antioxidant defenses and favor oxidative stress in relation with depressed Se-dependent GPX activities, we show that the epididymis is still efficiently protected against increasing peroxidative conditions. In this model, the caput epididymides of selenium-deficient animals showed a limited production of lipid peroxides, a total GPX activity which was not dramatically affected by the shortage in selenium availability and an increase in GPX5 mRNA and protein levels. Altogether, these data strongly suggest that the selenium-independent GPX5 could function as a back-up system for Se-dependent GPXs.     

Plasma and erythrocyte selenium and glutathione peroxidase activity in preterm infants at risk for bronchopulmonary dysplasia

The purpose of this study was to examine the relationships between selenium status, as measured by plasma and erythrocyte selenium and glutathione peroxidase (GPx) activity, and other postnatal factors, including selenium intake, gestational age, and oxygen dependence in preterm infants at risk for bronchopulmonary dysplsia. Eighteen preterm infants of 30 wk gestational age or less were included. At postnatal wk 1 and 4, selenium concentrations and GPx activity were measured and oxygen dependence and daily selenium intakes were determined from the medical chart. Plasma and erythrocyte selenium concentrations decreased from wk 1 to wk 4, whereas erythrocyte GPx activity increased. Increased selenium intakes during wk 1 were associated with increased erythrocyte GPx activity at both time-points, as well as a decreased need for supplemental oxygen on d 28. Preterm infants display increasing erythrocyte GPx activity despite declines in plasma and erythrocyte selenium. GPx activity might be enhanced by very early selenium supplementation.     

Post-translational activation of non-selenium glutathione peroxidase of Chlamydomonas reinhardtii by specific incorporation of selenium

Glutathione peroxidase (GPX) plays a pivotal role in the protection of cells against oxidative damage. The green alga Chlamydomonas reinhardtii expresses both selenocysteine-containing GPX and the non-selenium GPX homolog (GPXH). We previously reported that supplementation of selenium to algal culture induces GPXH to exhibit GPX activity. Here we investigated the incorporation of selenium into GPXH and its causal relationship with the upregulation of the enzymatic activity. GPXH was purified from algal cells grown with selenium and proteolytically digested into four fragments. Selenium content analysis for these proteolytic fragments confirmed that GPXH-incorporated selenium is predominantly enriched in a fragment that carries the putative catalytic residue Cys-38. We next constructed three kinds of engineered GPXH proteins by substituting Ser for one of three Cys residues in native GPXH, Cys-38, -66, and -84, using a bacterial overexpression system, resulting in Cys38Ser, Cys66Ser, and Cys84Ser derivatives, respectively. Of these, the Cys66Ser and Cys84Ser derivatives exhibited the same level of selenium-dependent GPX activity as the normal recombinant GPXH, whereas the Cys38Ser mutant GPXH not only lost its activity completely but also demonstrated severely impaired incorporation of selenium. These findings strongly suggest that selenium is post-translationally assimilated into the Cys-38 of the GPXH protein, thereby enhancing its enzymatic activity.     

Effect of physical restraint on oxidative stress in mice fed a selenium and vitamin E deficient diet

Physical restraint has been associated with increased oxidative damage to lipid, protein, and DNA. The purpose of this experiment was to determine whether physical restraint would further exacerbate oxidative stress in mice fed a selenium (Se) and vitamin E (VE) deficient diet. Three-week-old mice were fed a Torula yeast diet containing adequate or deficient Se and VE. Menhaden oil was added to the deficient diet to impose an additional oxidative stress. After 4 wk feeding, half the mice in each group were restrained for 5 d in well-ventilated conical tubes for 8 h daily. Mice fed the Se and VE deficient diets had increased liver thiobarbituric acid-reactive substance (TBARS) levels and decreased liver glutathione peroxidase (GPX1) activity and α-tocopherol levels. Plasma corticosterone levels were elevated in restrained mice fed the deficient diet compared to unrestrained mice fed the adequate diet. Restraint had no effect on liver TBARS or α-tocopherol levels. Liver GPX1 activity, however, was lower in restrained mice fed the adequate diet. In addition, liver superoxide dismutase (SOD) activity was lower in the restrained mice fed the adequate or deficient diet. Thus, under our conditions, Se and VE deficient diet, but not restraint, increased lipid peroxidation in mice. Restraint, however, decreased antioxidant protection in mice due to decreased activities of GPX1 and SOD enzymes.     

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.     

Dietary selenium status and plasma thyroid hormones in chicks

Experiments were conducted to study the effect of marginal levels of selenium and vitamin E on plasma thyroid hormones of meattype chicks. Plasma thyroxine (T₄) was significantly increased when a semipurified diet was supplemented with either selenium or vitamin E. Triiodothyronine (T₃) was also significantly increased by vitamin E and in one experiment with selenium supplementation. No significant increase in these hormones was observed in birds fed a corn-soybean-meal diet supplemented with these nutrients. Plasma corticosterone level was reduced and weight of the bursa of Fabricius increased by selenium or vitamin E supplementation. These nutrients may be necessary for providing the optimum thyroid conditions for activity of thyroid peroxidase.     

Effect of selenium and protein deficiency on selenium and glutathione peroxidase in rats

Twenty-four weanling male Wistar rats were divided into four groups fed diets containing adequate or deficient levels of selenium (0.5 ppm [+ Se] or <0.02 ppm [−Se] and protein (15% [+Pro] or 5% [−Pro]), but adequate levels of all other nutrients for 4 wk to determine the effects of Se deficiency and protein deficiency on tissue Se and glutathione peroxidase (GSHPx) activity in rats. Plasma, heart, liver, and kidney Se and GSHPx were significantly lower in Se-deficient groups in relation to Se-sufficient groups. In Se-deficient groups, Se and GSHPx were significantly higher in −Se−Pro rats in heart, liver, and kidney. Data analysis showed that there were significant interaction effects between dietary Se and protein on Se and GSHPx of rats. It is assumed that under the condition of Se deficiency. a low level of protein may decrease Se and GSHPx utilization, increase GSHPx synthesis, and result in Se redistribution. This could account for high levels of Se and GSHPx in the −Se−Pro rats compared to −Se+Pro rats.     

Effects of dietary selenium and tocopherol on glutathione peroxidase and superoxide dismutase activities in rat phagocytes

Glutathione peroxidase activities (GSH-Px) of peritoneal exudate polymorphonuclear neutrophils, pulmonary alveolar macrophages, and peritoneal exudate macrophages of rats depleted of dietary selenium for four to six weeks were markedly lower than the corresponding activities in rats fed the same diet supplemented with 0.5 ppm selenium as sodium selenite. GSH-Px in phagocytes from selenium-supplemented rats adequate or deficient in tocopherol status did not differ significantly. In selenium deficient animals, the residual GSH-Px of polymorphonuclear neutrophils and peritoneal macrophages, but not of alveolar macrophages were slightly higher in tocopherol-deficient rats than in tocopherol-supplemented animals. Superoxide dismutase activities of each cell type were comparable and were not significantly affected by dietary selenium or tocopherol.     

Plasma glutathione peroxidase activity and selenium levels of newborns with jaundice

The plasma glutathione peroxidase (GSH-Px) and selenium (Se) levels were determined in 31 newborns affected by jaundice (NWJ). The GSH-Px levels of both full-term and premature newborns exhibiting jaundice and having a birthweight lower than 2000 g were significantly low (p<0.05) when compared to controls. No significant differences were found in the corresponding Se levels, which were similar in all groups and independent of the pregnancy period and birthweight.     

Effects of dietary iron overload on glutathione peroxidase knockout mice

Excess iron (Fe) intake has been associated with an increased risk of cardiovascular disease in humans, presumably the result of increased oxidative stress. Previous work by us has shown that feeding a high-Fe diet to selenium (Se)-deficient weanling mice for 4 wk resulted in elevated plasma cholesterol and triglycerides and increased hepatic thiobarbituric acid reactive substances (TBARS). Here, we report the effect of Fe overload in mice lacking cellular glutathione peroxidase (GPX1 knockout [KO] mice), the selenoenzyme thought to account for much of the antioxidant action of Se. Four groups of 9–13 weanling wild-type (WT) or GPX1 KO mice were randomly assigned, then fed either an Fe-adequate (35 ppm Fe) or high-Fe (1100 ppm Fe) casein-based diet for 4 wk. Iron was added as ferric citrate. Both diets also contained 0.2 ppm Se added as sodium selenite. As expected, liver GPX1 activity was essentially absent in the KO mice. Another Se parameter measured (hepatic thioredoxin reductase activity) did not vary across groups. Although liver Fe was elevated in mice fed the high-Fe diet, liver TBARS was largely unaffected either by mouse genotype or diet fed. Moreover, plasma lipids were not elevated in the Fe-overloaded GPX1 KO mice. Thus, decreased GPX1 activity cannot account for the pro-oxidant hyperlipidemic effects observed earlier in mice fed the high-Fe Se-deficient diet. This suggests that impairment of Se functions other than GPX1 activity may be responsible for the elevated plasma lipids and hepatic TBARS seen in the Fe-overloaded Se-deficient mice.     

Levels of selenium in plasma and glutathione peroxidase in erythrocytes and the risk of breast cancer

Plasma selenium and glutathione peroxidase in erythrocytes were analyzed in a case-control study encompassing 441 cases with breast cancer and 191 controls with benign breast disease. No difference in mean serum selenium level between cases and controls on supplementary selenium intake was seen. If only individuals without supplementary intake, 278 cases and 135 controls, were considered a preventive effect was found increasing with selenium level. This finding was significant among women 50 years old or more with Mantel-Haenszel odds ratio=0.16 for individuals with serum selenium >1.21 μmol/L. Also for subjects with serum selenium in the range 1.00–1.21 μmol/L a significant preventive effect was seen with odds ratio=0.38. For women under 50 years of age a nonsignificant preventive effect was seen. Glutathione peroxidase in erythrocytes did not correlate well with serum selenium and was not a marker for the risk of breast cancer.     

Selenium metabolism and glutathione peroxidase activity in cultured human lymphoblasts

The metabolism of selenite, selenocysteine (SeCys), and selenomethionine (SeMet) was studied in three human lymphoblast cell lines with defects in the transsulfuration pathway and in control cells without this defect. There were very little differences in the induction of glutathione peroxidase (GPX) activity by selenite and SeCys among these cells. However, markedly higher levels of SeMet were required to induce GPX activity in transsulfuration defective cells than in control cells. Surprisingly, the addition of pyridoxal phosphate (PLP) to the media resulted in elevated GPX activity in all cells regardless of the chemical form of Se used. There is no explanation for this effect of PLP, but it is not through direct reaction with GPX or on the alteration of sulfhydryl groups.     

Low serum selenium concentration and glutathione peroxidase activity in intrahepatic cholestasis of pregnancy.

Serum selenium concentrations were found to be significantly lower in women with intrahepatic cholestasis of pregnancy than in women with normal pregnancies during the last trimester of pregnancy and post partum. The activity of the selenoenzyme glutathione peroxidase had a significant positive correlation with selenium concentration and it was also significantly lower in women with the disease. These findings suggest that selenium deficiency and reduced glutathione peroxidase activity are associated with the aetiopathogenesis of intrahepatic cholestasis of pregnancy.