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Selenium (Se) is an essential trace element of significant importance in human health. Diet is the major source of Se, and intake of this element depends on its concentration in food sources as well as the amount of those sources consumed. Unfortunately, daily dietary intake of Se in most European countries is generally low, ∼30-40μg/day, compared with the recommended dietary allowance, ∼55 and 70μg/day for adult females and males, respectively. The importance of Se as an essential trace element is linked to its role as selenocysteine in a number of selenoproteins including antioxidant enzymes glutathione peroxidases (GSH-Pxs), thioredoxin reductases (TrxRs), and selenoprotein P (SePP). These enzymes protect tissues against the damaging effect of reactive oxygen species (ROS) and other endogenous products of cellular metabolism implicated in DNA damage and potentially leading to mutagenesis, cell death, and carcinogenesis. Reduced body Se and antioxidant enzyme activity during pregnancy results in oxidative stress within tissues contributing to premature birth, miscarriage, preeclampsia, and intrauterine growth retardation. Because placenta development is highly dependent on oxygen status, uncontrolled ROS formation is likely detrimental. Despite these findings, the role of Se and Se-dependent enzymes in pregnancy remains controversial. The objective of this review is to explore Se status in pregnancy with respect to adverse outcomes. Effects related to decreased antioxidant activity and increased oxidative stress will be highlighted., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Oxidative stress plays a key role in numerous disease processes including chronic kidney disease (CKD). In general, oxygen metabolism leads to the formation of reactive oxygen species (ROS) dangerous to cells. Although enzymes and low-molecular-weight antioxidants protect against ROS, chronic imbalances of formation and elimination can eventually overwhelm endogenous defenses leading to deleterious consequences. In CKD, glutathione peroxidases (GSH-Px) play an important role in ROS metabolism. Plasma GSH-Px is synthesized in the kidney and requires selenium (Se) as a cofactor. Interestingly, Se and plasma GSH-Px are both significantly reduced in CKD, especially for those patients on hemodialysis. Supplementation of Se in these patients results in modest increases of GSH-Px, presumably from residual renal tissue. Kidney transplantation rapidly restores plasma GSH-Px. In this chapter, the relevance of these findings to CKD is explored with emphasis on renal disease processes and impact on attendant disorders including cancer and cardiovascular disease., (© 2015 Elsevier Inc. All rights reserved.)

Patients with chronic kidney disease (CKD) have an increased incidence of cancer. It is well known that long periods of hemodialysis (HD) treatment are linked to DNA damage due to oxidative stress. In this study, we examined the effect of selenium (Se) supplementation to CKD patients on HD on the prevention of oxidative DNA damage in white blood cells. Blood samples were drawn from 42 CKD patients on HD (at the beginning of the study and after 1 and 3 months) and from 30 healthy controls. Twenty-two patients were supplemented with 200 μg Se (as Se-rich yeast) per day and 20 with placebo (baker's yeast) for 3 months. Se concentration in plasma and DNA damage in white blood cells expressed as the tail moment, including single-strand breaks (SSB) and oxidative bases lesion in DNA, using formamidopyrimidine glycosylase (FPG), were measured. Se concentration in patients was significantly lower than in healthy subjects (P < 0.0001) and increased significantly after 3 months of Se supplementation (P < 0.0001). Tail moment (SSB) in patients before the study was three times higher than in healthy subjects (P < 0.01). After 3 months of Se supplementation, it decreased significantly (P < 0.01) and was about 16% lower than in healthy subjects. The oxidative bases lesion in DNA (tail moment, FPG) of HD patients at the beginning of the study was significantly higher (P < 0.01) compared with controls, and 3 months after Se supplementation it was 2.6 times lower than in controls (P < 0.01). No changes in tail moment was observed in the placebo group. In conclusion, our study shows that in CKD patients on HD, DNA damage in white blood cells is higher than in healthy controls, and Se supplementation prevents the damage of DNA.

Background: Numerous authors have shown that selenium (Se) concentration and glutathione peroxidase (GSH-Px) activity in plasma of chronic kidney disease (CKD) patients are lower than in healthy subjects, but there are only few publications on the level of GSH-Px protein in those patients and no reports on the effect of Se supplementation to HD patients on the level of this enzyme., Subjects and Methods: Se concentration and GSH-Px protein level in plasma were measured in a group of 30 CKD patients on hemodialysis (HD) supplemented with 200 microg Se/day for 3 months, and 28 patients on HD administered with placebo. Se concentration was measured by graphite furnace atomic absorption spectrometry and plasma GSH-Px protein level by the sandwich ELISA method using polyclonal antibody specific for human plasma GSH-Px., Results: Se concentration in patients on placebo did not change throughout the 3-month study period, but increased significantly in Se supplemented group. Se supplementation to CKD patients on HD had no effect on the level of GSH-Px protein., Conclusions: The lack of GSH-Px protein in CKD patients on HD is not linked to Se deficiency since the level of this element increased after Se supplementation while enzyme protein level did not change. The damaged kidney of HD patients is unable to synthesize GSH-Px, even after induction with selenium.

Selenium, as a component of few antioxidant enzymes, participates indirectly in elimination of reactive oxygen species and in antioxidative defense of the organism. There is a correlation between the concentration of selenium, activity of glutathione peroxidases (GSH-Px), and other parameters of antioxidative defense in blood components. The above mentioned factors were suggested to play an important role in etiopathogenesis of neoplastic diseases. Therefore, the aim of our present study was to compare the selenium status and GSH-Px activity in the plasma of 22 healthy women, 50 individuals suffering from cancer of uterine cervix, uterine corpus or ovary, and 49 women diagnosed with benign neoplasia of the uterine corpus or ovary. In addition, the selenium concentration was measured in postoperative cancer tissues, benign tumors, and histopatologically healthy surgical margins of the aforementioned patients. An average selenium concentration and GSH-Px activity in blood plasma of cancer patients and benign neoplasia patients was significantly lower than in the plasma of healthy women. It suggests that lower overall selenium status and lower selenium-dependent antioxidative capacity of the organism might partly contribute to development of neoplastic diseases of reproductive system. Postoperative tissues of patients revealed significantly higher selenium concentrations in cancer tissues of uterine cervix and corpus, and benign tumors of uterine corpus, as compared to corresponding healthy tissue margins. Higher accumulation of selenium in these neoplastic tissues might reflect a compensatory up-regulation of antioxidant defense systems in tumors that often undergo a persistent oxidative stress.

The metabolism of oxygen in aerobic organisms leads to generation of reactive oxygen species (ROS). These entities are able to oxidize almost all classes of macromolecules, including proteins, lipids and nucleic acids. The physiological level of ROS is usually regulated by antioxidant defense mechanisms. There are at least three groups of antioxidant enzymes: superoxide dismutases, catalases and glutathione peroxidases (GSH-Pxs) which neutralize ROS. The trace elements (copper, zinc and selenium) bound to the active sites of the above listed enzymes play an important role in the antioxidant defense system. In mammals, a major function of selenium (Se) and Se-dependent GSH-Pxs is to protect cells from oxidative stress. Selenium concentrations and GSH-Px activities are altered in blood components of chronic kidney disease (CKD) patients. The Se level is frequently lower than in healthy subjects and the concentration very often decreases gradually with advancing stage of the disease. Studies on red cell GSH-Px activity in CKD patients reported its values significantly lower, significantly higher and lower or higher, but not significantly as compared with healthy subjects. On the other hand, all authors who studied plasma GSH-Px activity have shown significantly lower values than in healthy subjects. The degree of the reduction decreases gradually with the progression of the disease. High inverse correlations were seen between plasma GSH-Px activity and creatinine level. A gradual decrease in plasma GSH-Px activity in CKD patients is due to the fact that this enzyme is synthesized predominantly in the kidney and thus the impairment of this organ is the cause of the enzyme's lower activity. Se supplementation to CKD patients has a slightly positive effect in the incipient stage of the disease, but usually no effect was observed in end-stage CKD. Presently, kidney transplantation is the only treatment that may restore plasma Se level and GSH-Px activity in patients suffering from end-stage CKD. A few studies have shown that in kidney recipients, plasma Se concentration and GSH-Px activity are restored to normal values within a period of 2 weeks to 3 months following surgery and thus it can be acknowledged that Se supplementation to those patients has a positive effect on plasma GSH-Px activity.

The dietary microelement selenium (Se) has been proposed as a potential chemopreventive agent for prostate cancer. This element is present in various amounts in all tissues. Little information is available on Se level in patients with prostate gland disorders. The levels of Se in prostatic gland of patients with prostate cancer, benign prostate hyperplasia, and healthy controls were examined. The Se level for benign prostate hyperplasia (156 +/- 30.6 ng/g) was the same as in the control group (157 +/- 26.0 ng/g), but in the gland of prostate cancer patients (182 +/- 34.1 ng/g wet weight), the Se level was significantly (p < 0.01) higher than in both healthy controls and benign prostate hyperplasia. Thus, the Se level in human healthy controls is lower than in kidney and liver but higher compared with other tissues.

Prostate cancer (PC) is the most common cancer in men and a leading cause of cancer death. Prostatic gland accumulates reasonably high amount of selenium (Se), the element that prevents the development of PC. It is hypothesized that some selenoproteins inhibit the transformation of normal prostate epithelium into neoplasm. We studied Se levels in whole blood, plasma and prostate of 32 PC and 40 benign prostate hyperplasia (BPH) patients and in the control group composed of 39 healthy subjects. The selenoenzyme glutathione peroxidase (GSH-Px) was also measured in the patients' red cells, plasma and prostate tissue. Se concentration in whole blood and plasma in both groups of patients was lower as compared with controls, while in prostate gland it was significantly higher in PC than in BPH patients and controls. Red cell GSH-Px activity was the same in PC patients and controls but significantly lower in BPH patients. Plasma GSH-Px activity was significantly lower in PC patients than in the control group, and prostate GSH-Px activity was significantly lower in PC patients as compared with BPH patients. Since Se has anticancer properties, it is very likely that its low level in blood may facilitate the development of cancer. A higher level of Se in prostate of PC patients has no influence on GSH-Px activity in the gland.

This study focuses on glutathione (GSH) level in red blood cells, as well as on glutathione peroxidases (GSH-Px) activities in red blood cells and in plasma of chronic renal failure (CRF) patients following renal transplantation. We want to focus our main attention on plasma GSH-Px, the selenoenzyme that is synthesized primarily in the kidney. In CRF patients, activity of this enzyme is significantly reduced, and the reduction decreases with the progress of the disease, reaching in the end-stage 20% to 30% of the activity of healthy patients. We have shown that following renal transplantation the activity of plasma GSH-Px is restored very rapidly, and 2 weeks after surgery it reached the value of the control group. Red blood cell GSH level is significantly higher in CRF patients, and following transplantation, no significant changes were observed. Red blood cell GSH-Px activity before transplantation was the same as in healthy patients and did not change significantly after surgery.

In patients with chronic renal failure (CRF) Se concentration in blood components is usually lower as compared with healthy controls. One of the five known forms of Se-dependent glutathione peroxidases (GSH-Px), the plasma GSH-Px, is synthesized primarily in the kidney. In CRF patients, plasma GSH-Px activity is reduced and the reduction increases with the progress of the disease. The Se concentration in blood components was measured spectrofluorometrically with 2,3-diaminonaphthalene as complexing reagent. Activities of GSH-Px in red cells and in plasma were assayed by the coupled method with t-butyl hydroperoxide as substrate. The study group consisted of 150 patients in different stages of CRF. The results were compared with the values for 30 healthy subjects. Se concentrations in whole blood and plasma of the entire group of patients were significantly lower (p < 0.01) as compared with the healthy subjects. In the incipient stage, however, the Se levels in all blood components were non-significantly lower. In whole blood and plasma the Se levels gradually decreased, reaching in the end stage values that were lower by 29 to 32% (p < 0.0001) as compared with the control group. Total protein and albumin levels in plasma of patients were significantly lower (p < 0.0001) as compared with healthy subjects and they decreased linearly with the progress of the disease. Positive and highly significant correlations were noted between total plasma protein and plasma Se concentrations (p < 0.0001) as well as between plasma albumin and plasma Se concentrations (p < 0.0001). Red cell GSH-Px activity in the entire group of patients was lower (p < 0.05) than in the control group and did not change significantly with the progress of the disease. In plasma, however, GSH-Px activity of the entire group was lower by 33% (p < 0.0001) as compared with healthy subjects and decreased gradually with increasing renal failure. Highly significant, inverse correlations were seen between creatinine levels and plasma GSH-Px activities (p < 0.0001) as well as between urea nitrogen levels and plasma GSH-Px activities (p < 0.0001) when all stages of the disease were included. In conclusion, patients with CRF exhibit lower Se levels in blood components as compared with healthy subjects. In whole blood and plasma these levels decrease with the progress of the disease. Plasma GSH-Px activity in patients was extremely reduced and it dramatically decreased with the progress of the illness.

In animals and humans, the highest level of selenium (Se) occurs in the kidney. This organ is also the major site of the synthesis of the selenoenzyme glutathione peroxidase (GSH-Px). Decreased Se levels and GSH-Px activities in blood are common symptoms in the advanced stage of chronic renal failure (CRF). Blood samples for Se levels and GSH-Px activities measurements from patients were collected just before transplantation and 3, 7, 14, 30, and 90 d posttransplant. The Se levels in whole blood and plasma of patients before transplantation (79.5 and 64.5 ng/mL, respectively) were lower by 23% and 21%, respectively, as compared with controls (p < 0.0001), and 7 d after operation, it further decreased in both components (p < 0.01). Fourteen days after surgery, the levels reached the initial values and increased slowly in the later period. Red blood cell GSHPx activity in patients in the entire period of the study did not differ from the control group. Plasma GSH-Px of patients before the surgery was extremely low (76 U/L) as compared with controls (243 U/L; p < 0.0001) but increased rapidly to 115 U/L after 3 d, to 164 U/L after 14 d, and to 208 U/L after 3 mo posttransplant. In CRF patients, after kidney transplantation, plasma GSH-Px activity increased rapidly, approaching, after 3 mo, the values that were close to the normal levels. A negative correlation between creatinine level and plasma GSH-Px activity is observed in patients after kidney transplantation. Monitoring of plasma GSH-Px activity may be a useful additional marker of the transplanted kidney function.

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 GSHPx activity. The study group comprised 53 CRF patients at various stages of the disease supplemented with Se (200 microg/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 GSHPx 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.

Aim: In our study we measured selenium concentration in the blood of women with diagnosed cancer and benign tumors. The results were compared with healthy women. Some other parameters of the antioxidant system in all studied groups were also investigated, namely, activity of glutatione peroxidase, superoxide dismutase, as well as the levels of glutathione and malondialdehyde., Material and Methods: All parameters were determined in peripheral blood of (a) 47 women with diagnosed cancer (b) 46 women with diagnosed benign tumors, and (c) 20 healthy women (control group). Statistical analysis of the results was performed using "Statistica" software., Results: Our results showed lower selenium concentration in the whole blood and plasma of cancer and benign tumor patients as compared to healthy women. An activity of glutathione peroxidase in erythrocytes and plasma were also lower in both patients' groups than in the control group. Statistical analysis of data revealed a positive correlation between selenium concentration and glutathione peroxidase activity in plasma. Lower activity of superoxide dismutase and increased concentration of malondialdehyde was noted in plasma of cancer patients as compared to healthy women., Conclusions: 1. A status of antioxidant systems plays an important role in carcinogenesis. 2. The antioxidant system of the women suffering from cancer is deficient. 3. A capacity of that system depends greatly on the concentration of antioxidants and activity of antioxidant enzymes, among them glutathione peroxidase.

Disturbances in the antioxidant system could play a role in pathogenesis of chronic liver disease. The aim of our study was to evaluate the levels/activities of antioxidants in blood of patients with chronic liver disease. We estimated selenium and glutathione concentrations and glutathione peroxidase activities in blood of 59 patients with chronic hepatitis B or C virus infection (group 1) and 64 patients with alcoholic, autoimmune or cryptogenic chronic liver disease (group 2). The results were compared with 50 healthy controls. Whole blood and plasma selenium and red cell glutathione concentrations were significantly lower in the patients compared with the controls. Red cell glutathione peroxidase activity was slightly reduced in both subgroups of group 1 and in group 2 with normal alanine aminotransferase values. Plasma glutathione peroxidase activity was slightly but significantly higher in patients with elevated aminotransferase values. The findings suggest that disturbances in antioxidant parameters in blood of patients with chronic liver disease may be the cause of the peroxidative damage of cells.

The effects exerted on hepatocytes by alcohol metabolites, drugs or other toxins and also hepatotropic viruses lead to chronic liver diseases. Reactive oxygen species (ROS) have been implicated in a number of pathologies, including different types of liver diseases. Organism has developed several mechanisms to counteract or prevent reactive oxygen species effects. These include enzymes such as: glutathione peroxidase (GSH-Px) with selenium (Se) in the active site and glutathione S-transferase (GST). Measurement of GST, compared with alanine aminotransferase (AIAT), has been advocated as a superior marker of hepatocellular damage. The aim of this study was to assess selenium concentration, glutathione peroxidase and glutathione S-transferase activities in plasma of patients with various types of liver diseases. The study population consisted of 54 patients and 25 healthy volunteers. The patients were divided into two groups according to etiology of the disease. Plasma selenium concentration was reduced in patients with cirrhosis, as compared to controls, irrespective of etiology and activity of AIAT. Plasma GSH-Px activity was significantly lower in both groups of patients with normal AIAT activity, whereas it was higher in both groups with activity of AIAT higher than 40 U/l. GST activity was higher only in post-viral group in patients with high AIAT activity. Impaired intestinal absorption and distribution of selenium among plasma proteins have been suggested as possible mechanism of reduced selenium concentration. Changes in the activities of glutatthione-dependent enzymes in plasma may arise from increased formation of reactive oxygen species or from release of these enzymes from injured hepatocytes to plasma.

Background: Human milk is the only natural source of food for infants during the first several months of life. The milk should contain all trace elements in adequate amounts, including selenium (Se). Se is of particular interest because the daily requirement for this element in infants is higher due to their rapid growth. The aim of our study was to determine the Se concentration in human milk and to calculate the daily Se intake by breast-fed infants in western Poland., Material and Methods: The Se concentration was assayed in mature human milk (14 to 58 days after parturition) collected from 352 lactating women living in 7 voivodeships in western Poland. The concentration of Se was measured by the fluorometric method with 2,3-diaminonaphthalene as a complexing reagent. The values were expressed as ng/ml., Results: No significant differences were observed in terms of Se concentration among the milk samples collected from the different voivodeships. However, the highest values were obtained in the northern part of the region. The mean Se concentration was 10.51 +/- 2.76 ng/ml (range: 10.41-10.65 ng/ml). The calculated mean daily Se intake by breast-fed infants was 7.71 microg/day (range: 3.67-17.17 microg/day)., Conclusions: The Se concentration in human milk in the region studied here is uniform, but the daily Se intake of breast-fed infants in the western part of Poland is lower than the recommended daily requirement. The reason for this situation would appear to be low Se content in the soil, and consequently in the foodstuffs from this region.

The authors obtained tissue samples taken at autopsy from 46 healthy individuals killed in accidents and from 75 corpses of victims of various diseases to analyze selenium levels. The per-weight-unit basis of selenium levels (all expressed as ng/gm wet tissue) in tissues decreased in the following order: kidney (469) > liver > spleen > pancreas > heart > brain > lung > bone > skeletal muscle (51). The highest proportion of body selenium was found in skeletal muscles (27.5%); much less selenium was found in bones (16%) and blood (10%). In the tissues of cancer corpses, the selenium levels were much lower than levels in controls. The lowest selenium levels were found in the livers of alcoholics. Tissue selenium levels found in the study were significantly lower than levels reported in Japan, United States, Canada, and other countries. The low selenium levels in the tissues of Polish residents result from inadequate selenium levels in the soil. The authors used selenium levels in tissues to calculate the amount of selenium in humans in Poland (i.e., approximately 5.2 mg). This level was similar to levels found in New Zealand (i.e., 3.0-6.1 mg), but it was lower than the mean level found in Germany (i.e., 6.6 mg) and in the United States (i.e., 13.0-20.3 mg).

Background: Among the tissues of humans the highest level of selenium (Se) is found in the kidney and the lowest in the muscle. The Se level in tissues is age-dependent., Aim: To measure the Se level in kidney, liver and heart of newborns and infants who were born in different periods of pregnancy and died of various diseases., Subjects: Tissues obtained from 49 infants deceased at 1 day to 2.5 months of age. Forty-five of them were premature infants born between 23 and 36 weeks of pregnancy, four were born at term., Results: Se levels in kidney and heart (but not liver) increased gradually with the duration of pregnancy. Positive and significant correlations were found between the weeks of pregnancy and Se levels in kidney (r=0.433, P=0.023) and heart (r=0.313, P=0.030). In the total group, the mean Se levels in the kidney (185+/-64.7 ng/g wet weight) and liver (177+/-59.8 ng/g) were two times higher than those in the heart (90.5+/-33.7 ng/g). In this study, the Se levels in kidney and liver were from 2.5 to 1.2 times lower than the values found in our previous study for healthy adult victims. In the heart, the Se levels were similar in infants and adults. No significant differences were found in the mean Se levels in the various tissues in infants who died due to respiratory distress syndrome, congenital heart disease, other diseases and the group as a whole. The low levels of Se in the tissues studied by us, as compared with data from other countries, are probably due to lower Se intake by pregnant women in Poland., Conclusions: This study demonstrates that Se level in kidney and heart, but not in liver, increases with the progress of pregnancy. The Se level in kidney and liver is two times higher compared with heart and significantly higher than in adult subjects.

Background: Aim of the study was to determine the concentration of selenium (Se) and the activity of glutathione peroxidase (GSH-Px) in patients with acute myocardial infarction (AMI) and to observe the behavior of these parameters during thrombolysis therapy., Material and Methods: The study comprised two groups of AMI patients and a control group. The first group consisted of 49 patients from whom blood samples were taken after admission to the intensive care unit and subsequently after 3, 7, 14 and 30 days of hospitalization. In the second group of patients (n = 18) blood was taken for measuring only the GSH-Px activity in plasma. In this group blood samples were collected after admission to the hospital, 6, 12, 24, 48 hours, 3, 7, 14 and 30 days later. Control group comprised of 58 healthy subjects. Se levels in whole blood and plasma were measured spectrofluorometrically with 2,3-diaminonaphthalene as a complexing reagent. GSH-Px activity in red cells and plasma was measured spectrofluorometrically with t-butyl hydroperoxide as substrate., Results: In the first group of patients Se concentrations in whole blood and plasma as well as GSH-Px activities in red cells and plasma did not differ significantly from healthy subjects. Both Se levels and GSH-Px activities were stable during the entire period of the study. In the second group of patients, however, plasma GSH-Px activity increased after admission and reached the highest value after 48 hours. This activity was significantly higher compared to healthy subjects (p < 0.004) and to the mean initial activity of this group (p < 0.02). In the later period the activity decreased to the values of healthy subjects., Conclusion: We suggest that the increased activity of GSH-Px in plasma of AMI patients is the response of the organism to the increased levels of reactive oxygen species produced during reperfusion and thrombolysis.

Objective: To investigate the selenium glutathione and glutathione peroxidase (glutathione-Px) levels in blood in women who experience miscarriage., Design: An observational study., Participants: Forty women with miscarriage occurring in the first and second trimesters., Methods: Concentrations were measured in whole blood and plasma. Glutathione was measured in red cells and glutathione-Px activity was measured in the red cells and plasma. The results were compared with 36 women in the same period of viable pregnancy and 28 age-matched, healthy, non-pregnant controls., Results: The selenium concentrations in whole blood and plasma of women following abortion were the same as in viable pregnancy, but were significantly lower compared with controls. The glutathione levels were significantly higher in women with miscarriage compared with viable pregnancies and with non-pregnant women. Red cell and plasma glutathione-Px activities of women who had had a miscarriage were significantly lower than in both normal pregnancies and the control group., Conclusion: The decreased activities of the antioxidant enzymes, red cell and plasma glutathione-Px, may play an important role in the aetrology of spontaneous abortion.

In the present study several parameters associated with oxidative stress were examined in the blood of 25 chronic renal failure (CRF) patients and the results were compared with 18 healthy subjects. Mean creatinine concentration in patients was 1,216 +/- 292 micromol/l. Selenium (Se) concentration in red cells, whole blood and in plasma of CRF patients (106 +/- 32.5, 59.0 +/- 16.7 and 42.4 +/- 13.8 ng/ml, respectively) was significantly (0.0001 < P 0.01) lower (by 20-42%) compared with the controls. Red cell and plasma glutathione peroxidase (GSH-Px) activities (16.6 +/- 3.4 U/g Hb and 93.7 +/- 32.9 U/l plasma) were lower by 12 and 53% (P < 0.05 and < 0.0001, respectively) in patients than in healthy subjects. GSH concentration in red cells of patients (2.81 +/- 0.45 mmol/l) was significantly (P < 0.001) higher (by 20%) than in control group. Malonyldialdehyde (MDA) concentration (expressed as thiobarbituric acid-reactive substances) in red cells of patients (725 +/- 155 nmol/g Hb) was significantly (P < 0.001) higher (by 28%) than in control group. No significant difference was observed in the activity of superoxide dismutase in pLasma between the two groups. In conclusion, our results confirm that the aLterations in Se levels in blood components and in GSH-Px activity in plasma show that the kidney plays an important role in Se homeostasis and in plasma GSH-Px synthesis.

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 microg 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.

A total of 905 human milk samples collected in all provinces of Poland, between 12 and 75 days of lactation, were analyzed for selenium concentration. The distribution of Se levels in milk between the provinces was narrow and varied from 8.81 to 11.58 ng/mL, with the mean value (+/- SD) of 10.24 +/- 2.82 ng/mL. The regions with lower levels of Se were in the central and eastern part of Poland; the areas with higher values were in the northern, western, and southern parts of Poland. No significant correlations were found between Se levels in milk and the age of lactating mothers or between Se levels and the postpartum period. The calculated daily Se intakes by breast-fed infants varied from 6.46 to 8.50 microg/day, with the mean value of 7.52 microg/day. This amount does not meet the recommended dietary allowances for infants between 0 and 6 months of age. Based on Se levels in human milk, we present a selenium map of Poland.

Patients with chronic renal failure often have a reduced level of blood selenium. Decreased glutathione level, and the activity of glutathione peroxidase and superoxide dismutase are also lowered. As the effect of these alterations the concentration of malondialdehyde, a marker of the oxidative degradation of polyunsaturated fatty acids, is increased. In patients undergoing regular haemodialysis some of the above mentioned parameters are restored. In dialyzed patients with extremely low concentration of selenium, the administration of this element is recommended.

The aim of this study was to determine the effect of selenium (Se) supplementation to lactating women on Se concentrations and glutathione peroxidase (GSH-Px) activities in blood components of mothers and breast-fed infants and on milk Se levels and Se intake by breast-fed infants. Lactating mothers were supplied for 3 months with 200 micrograms Se/day in the form of yeast-Se (Y-Se) and sodium selenite. Initial blood and plasma Se levels of all women (n = 67) were 76.6 and 53.2 micrograms/L, respectively. After 3 months Se concentrations both in whole blood and in plasma from mothers and infants were significantly higher than the initial values. Y-Se exerts a stronger effects than selenite on blood and plasma Se levels. Initial milk Se concentration was 8.9 micrograms/L and after 1 month in both groups in reached a plateau at 14-16 micrograms/L. This resulted in an increase of Se intake in breast-fed infants from 6.1 to a plateau of 11-13 micrograms Se/day. GSH-Px activities in plasma and red cells of Y-Se group increased significantly and reached a plateau after 1 and 2 months, respectively, while in the selenite group the enzyme activities increased steadily throughout the entire period of the study. Selenite exerts a stronger effect on GSH-Px both in maternal and in infant blood components as compared with Y-Se. In milk the GSH-Px activity in the Y-Se group did not change during the study, while in the selenite group after 3 months it increased almost 2-fold compared to the initial value. In conclusion, this study shows that organic Se causes higher Se deposition than did the inorganic form.

The Se concentration in maternal and cord whole blood and plasma was determined spectrofluorimetrically in: (1) 42 women at term and (2) 46 at preterm parturients, and in the placenta. The glutathione peroxidase (GSH-Px) activity was measured in red cells and plasma in maternal and cord blood of both groups. The Se concentrations and GSH-Px activities of the above-mentioned groups were compared with those of non-pregnant women. Whole blood and plasma Se concentration of parturients at term did not differ significantly from those of non-pregnant women (72.3 versus 80.3 ng ml-1 whole blood and 48.7 versus 56.2 ng ml-1 plasma). In preterm parturients, however, Se concentrations were significantly lower (61.1 ng ml-1 whole blood and 39.2 ng ml-1 plasma) when compared with term parturients. The Se levels in cord blood and plasma were similar to their mothers' Se concentrations. No difference was observed in placenta Se levels (130 ng g-1 wet weight in both groups). The same was true for glutathione (GSH): the concentration in maternal and cord blood of term and preterm parturients did not differ and varied from 2.43 to 2.50 mmol l-1 red cells. Red cell GSH-Px activities were similar in maternal and cord blood of both term and preterm groups and ranged from 14.3 to 15.7 U g-1 Hb. The plasma enzyme activity in the maternal blood of preterm parturients was significantly (p < 0.05) lower than that of mothers at term delivery. The GSH-Px activity in the plasma of cord blood was significantly (p < 0.001) lower in the preterm than in the term group. It is suggested that low Se levels in the blood of women at preterm delivery, as shown here, may be one of the causes of retinopathy and respiratory distress syndrome in preterm infants.

We studied the selenium (Se) concentration in whole blood and plasma, glutathione peroxidase (GSH-Px) activity in red blood cells and plasma, as well as both of these parameters in cancerous and tumor-free lung tissue of lung cancer patients. Blood samples were taken from 84 cancer patients and 61 healthy controls. Normal and neoplastic lung tissues were obtained from 57 patients at the time of surgery. Se concentrations in whole blood and plasma were lower by 23% (p < 0.001) in patients compared with controls. GSH-Px activity in red cells was lower by 20.2% (p < 0.004) and in plasma by 11.7% (p < 0.05) in patients than in the control group. On the other hand, the tumor Se level was higher by 66.6% (p < 0.0001) and GSH Px activity by 49.5% (p < 0.0001) than in adjacent tumor-free tissue. No differences in Se concentrations and GSH-Px activities were found between squamous cell carcinoma and adenocarcinoma nor among the clinical stages of the disease. In the whole blood and plasma of cancer patients significantly lower Se concentrations were found in smokers than in nonsmokers. Significantly lower Se concentrations were also found among cancer patients who were smokers compared with controls. These findings show that in the blood of cancer the antioxidant ability, as measured by Se and GSH-Px, is reduced significantly. The cause of increased Se and GSH-Px in the malignant part of the lung is not understood and requires further studies.

The objective of this study was to evaluate the effect of selenium (Se) supplementation on Se concentration and glutathione peroxidase (GSH-Px) activity in blood components and seminal fluid and on spermatozoal quality characteristics in subfertile men. Thirty-three men were supplemented for 12 weeks with 200 micrograms Se/day in the form of yeast-rich Se (group I, n = 16) or sodium selenite (group II, n = 17). Blood samples and sperm were collected at the start of the study and after 2, 4, 8, and 12 weeks following Se supplementation. Se concentration in whole blood and plasma and GSH-Px activity in red cells and plasma increased significantly during the study, but in the group supplemented with yeast-Se the effect was more pronounced. Se concentration in seminal fluid also increased in both groups, but the effect of yeast-Se was markedly higher than that of selenite. In both groups statistically significant correlations were found between Se concentration in plasma and seminal fluid. GSH-Px activity in seminal fluid in the yeast-Se group increased significantly and reached a plateau after 2 weeks, whereas in the selenite group the activity did not change throughout the whole study period. Weak correlations between Se concentrations and GSH-Px activities in seminal fluid were seen, but only in the yeast-Se group were the relations statistically significant. The subjects in both groups showed no response in sperm count, motility, and morphology. In conclusion, we can ascertain that the supplementation of subfertile men with yeast-rich Se showed a more pronounced effect on Se concentrations and GSH-Px activities in blood components and seminal fluid than selenite did. Se supplementation did not improve the spermatozoal quality characteristics of sperm count, motility and, morphology.

The paper describes the up-to-date knowledge on the essential trace element, selenium, in human nutrition, its concentration in blood during pregnancy and in milk during lactation. Changes in selenium concentration in maternal milk during various stages of lactation and selenium concentration in infant blood as well as the selenium intake by breast- and formula-fed infants is discussed.

Selenium concentrations in the full blood and erythrocyte and plasma GSH-Px activity were determined in patients with cancer of the stomach, colon and rectum. The results were compared with those in the group of healthy subjects. Blood samples were collected into heparinized tubes prior to surgery. Selenium concentrations in the full blood and plasma were lower (75.5 ng/mL and 56.2 ng/ml, respectively) in patients with the cancer of the stomach than healthy subjects (99.5 ng/ml and 78.5 ng/mL, respectively; p < 0.0001). Concentration of this element in both full blood and plasma was also lower in patients with cancer of the colon and rectum (77.7 ng/mL and 61.0 ng/ml, respectively; p < 0.0001). Erythrocyte and plasma GSH-Px activity was also significantly lower (p < 0.001) in patients with cancer of the stomach than in healthy subjects, and amounted to 13.6 U/g Hb and 188 U/L, respectively. Activity of this enzyme in patients with cancer involving lower segment of GI tract amounted to 15.9 U/g Hb and 190 U/L of plasma, and was significantly lower (p < 0.001) than in normal subjects in whom it amounted to 21.0 U/g Hb and 256 U/L of plasma.

Experiments were conducted to examine selenium (Se) metabolism in tissues of lambs following Se supplementation at varying doses. For three months four groups of lambs were fed either a basal diet (group A) containing 0.082 mg Se per kg dry matter (ppm) or the same diet plus mineral mixture with Se (as selenite) so that the total diet contained 0.25, 0.41 and 0.58 ppm Se (groups B, C and D, respectively). After three months six lambs of each group were slaughtered and tissues were removed for Se level and GSH-Px activity determinations. Among the tissues of lambs fed the basal diet the highest Se concentration was found in the kidney (1.32 micrograms/g wet weight), and the lowest in the skeletal muscle (0.030 micrograms/g wet weight). In the liver, heart, lung and spleen Se concentrations were almost at the same level and varied in the range of 0.14 to 0.18 micrograms/g wet weight tissue. No increase in Se concentration was found in the kidneys of Se-supplemented animals. Se concentration in the liver and lung increased linearly with the Se level in the diet. In the spleen, heart and skeletal muscle the highest Se concentrations were found in lambs fed 0.41 ppm Se. Tissue GSH-Px activities (calculated on the per g protein basis) increased significantly in Se-treated animals. In the tissues of lambs fed 0.25 ppm Se the enzyme activities were higher in a range of 1.8 to 3.5 as compared to the group fed the basal diet. Higher doses of dietary Se had much smaller effect on the tissues GSH-Px activity.(ABSTRACT TRUNCATED AT 250 WORDS)

A chromatographic method is described to determine the distribution of selenium between selenoprotein P, glutathione peroxidase (GSH-Px), and albumin in plasma, using two small columns of heparin-Sepharose and reactive blue 2-Sepharose linked together in tandem. One milliliter of plasma was diluted to 12 ml with 0.02 M sodium phosphate buffer, pH 7.0 (the equilibration buffer), applied to the heparin-Sepharose column, and eluted at a flow rate of 30 ml per hour. GSH-Px was not retained by either of these columns but selenoprotein P was retained by heparin-Sepharose and albumin by reactive blue. After the two columns were separated, selenoprotein P was eluted with heparin from heparin-Sepharose and albumin eluted from reactive blue with high salt. Analytical work confirmed the presence of selenoprotein P, GSH-Px, and albumin in the respective fractions. When rats were injected with 75Se as either selenite or selenomethionine most of the radioactivity was incorporated into the selenoprotein P fraction, with the next greatest amount into GSH-Px, and the least amount into albumin. Slab gel electrophoresis was used to determine that most of the selenium in each of the three fractions was associated with each of these selenium containing proteins. This method indicated that the majority of the selenium in plasma is associated with selenoprotein P, and the only time this was found not to be true was with high levels of dietary selenomethionine.

Whole-blood and plasma selenium (Se) concentrations, red blood cell and plasma glutathione peroxidase activities, and red blood cell glutathione concentrations were investigated in 49 healthy pregnant women. Mean whole-blood and red blood cell Se concentrations started to decline after the 16th week and plasma Se after the 26th week of pregnancy. The lowest values were noted just before delivery. Negative correlations were found between the gestational age and both whole-blood and plasma Se concentrations: (r = -0.560 (p < 0.001) and r = -0.553 (p < 0.001), respectively. Plasma and red blood cell glutathione peroxidase activities started to decrease after the 20th and 30th week of pregnancy, respectively, and before delivery were significantly lower (p < 0.001) than during the 10th week of pregnancy. The red blood cell glutathione concentration increased significantly just before delivery. These results seem to confirm the supposition that in pregnant women with low or even moderate blood Se concentrations the requirement for the element significantly increases.

Selenium (Se) is an essential trace element for animals and humans. Its biological role was established following the discovery that Se is a structural component of the active center of the enzyme glutathione peroxidase (GSH-Px). During the last decade remarkable progress has been made in the recognition of the structure and function of several selenoproteins. Cellular GSH-Px was the first enzyme recognized as a selenoprotein. In it Se was found in the form of selenocysteine. The enzyme is a tetrameric protein and is composed of four apparently identical subunits each containing one gram atom of Se. Plasma GSH-Px also has a tetrameric form with identical subunits and with one atom of Se per subunit. It is, however, a glycosylated protein, and is distinct from cellular enzyme. Both enzymes catalyze the reduction of hydrogen peroxide and a variety of organic hydroperoxides by glutathione. A third GSH-Px, called phospholipid hydroperoxide glutathione peroxidase (PHGSH-Px), is a monomeric, membrane-associated enzyme containing one atom of Se per mole of protein. This enzyme destroys esterified lipid hydroperoxides. The fourth known mammalian selenoenzyme is a type I iodothyronine 5'-deiodinase that catalyzes the deiodination of L-thyroxine to the biologically active hormone 3,3',5-triiodothyronine. It is a monomeric enzyme and contains one atom of Se per mole of protein. Selenoprotein P, a fifth known selenoprotein, is a glycosylated, monomeric protein containing ten atoms of Se per molecule. The function of this protein is not known, but it may play a role in Se transport or be connected with a protective activity against free radicals. In all these selenoproteins the Se is incorporated into the protein molecule via the selenocysteinyl-tRNA which recognizes the specific UGA codons in mRNAs to insert selenocysteine into the primary structure of selenoproteins.

Selenium (Se) levels in whole blood and plasma, and glutathione peroxidase (GSH-Px) activities in red cells and plasma were measured in ewes fed an Se-deficient diet injected with barium selenate before breeding season. Highly significant increases in Se levels and GSH-Px activities (P less than 0.001) were observed throughout the gestation period and during lactation. In the control group, Se levels and GSH-Px activities decreased significantly (P less than 0.001), and were at critically low levels during lambing and lactation periods.

Recent prospective epidemiological studies have shown an association between a low prediagnostic serum selenium (Se) concentration and the risk of cancer. Se concentrations in whole blood and plasma, and the activity of red cell and plasma glutathione peroxidase (GSH-Px) were measured in patients with breast cancer, gastric cancer and colorectal cancer. The observed whole blood and plasma Se concentrations of healthy persons were 99.5 and 78.5 micrograms/L, respectively. Red cell and plasma GSH-Px activities of this group were: 21.0 U/g Hb and 256 U/L plasma. In all investigated cancer patients significantly lower whole blood and plasma Se concentrations, and significantly lower red cell and plasma GSH-Px activities were found, as compared with the values of healthy controls. Low Se concentrations of blood components may be indicative of increased cancer risk.

For three months four groups of sheep were fed either a basal diet (group A) containing 0.082 ppm selenium (Se), or this diet plus mineral mixture with Se (as selenite) so that the total diet contained 0.25, 0.41 and 0.58 ppm Se (groups B, C, and D, respectively). The Se concentration and GSH-Px activity in red cells were determined at the commencement of the study and at monthly intervals. While in the control group the Se level and GSH-Px activity did not differ throughout the study, in the experimental groups both Se accumulation and GSH-Px activity were elevated. In group B the increase in Se concentration was linear throughout, while in groups C and D great accumulation was observed in the first month and lower in the subsequent period. In all Se-supplemented groups, the red cell GSH-Px increased linearly throughout the study, but no significant differences were found between groups B, C and D. The mean elevations of the enzyme activities were: 58 +/- 8%, 142 +/- 5% and 192 +/- 7% of the initial values after 1, 2 and 3 months of the study, respectively. These data show that the amount of 0.25 ppm Se in the sheep diet satisfy the requirement of the erythropoietic systems to synthesize the enzyme.

Red blood cell glutathione peroxidase (GSH-Px) activity of six patients with phenylketonuria treated with aminoacid mixture and protein hydrolysate diets was significantly lower (11.2 IU/g Hb) than that of 21 age-matched healthy children (14.9 IU/g Hb). When the diets were supplemented with yeast rich in selenium the red blood cell GSH-Px activity increased already after one month of treatment to 16.1 IU/g Hb (P less than 0.001) and remained at that level during subsequent two months of selenium supplementation. A high significantly positive correlation has been found between calculated red blood cell selenium level and GSH-Px activity within three months of selenium supplementation.

Concentration of selenium in whole blood and plasma, lipid peroxides in plasma, and glutathione peroxidase activities in red blood cell hemolysates and plasma were determined in 49 coal power plant workers and in 50 rubber factory workers. The results were compared with those obtained for 58 nonindustrial controls. Whole blood selenium was significantly lower and plasma lipid peroxides were significantly higher in power plant workers when compared to the nonindustrial group. In the rubber factory workers, whole blood selenium and red blood cells and plasma glutathione peroxidase activities were significantly lower than in the control group. Urinary output of selenium was also significantly decreased in rubber factory workers. Slightly elevated lipid peroxides were also observed in that group. It seems reasonable to conclude that the lower blood selenium and decreased urinary output of this element may result from increased loss of selenium with perspiration. No correlation has been observed between selenium concentration and glutathione peroxidase activity and between enzyme activity and lipid peroxides concentration in the industrial group.

Selenium (Se) concentrations in whole blood and plasma of 19 nonpregnant women. 14 mothers at delivery, 14 neonates, and 13 infants, aged 2-12 mo, were evaluated. The activity of glutathione peroxidase (GSH-Px) in erythrocytes and plasma and the level of lipid peroxides in plasma were also analyzed. Selenium concentrations in whole blood and plasma in mothers at delivery were significantly lower compared to nonpregnant women. Selenium concentrations in cord blood components were lower compared to mothers, but the differences were not significant. The concentration of the element decreased in the first few months of life. Glutathione peroxidase activity in erythrocytes differed only slightly in the examined groups. In plasma, however, the enzyme activity was significantly lower in pregnant compared to nonpregnant women and in neonates compared to their mothers. Lipid peroxide concentrations in plasma differed only slightly in the examined groups. The results obtained are discussed in terms of the observations of other investigators.

Selenium (Se) levels in whole blood, red blood cells, and plasma taken from 199 healthy subjects were investigated and found to be 101.1 micrograms/1 (whole blood), 133.1 micrograms/1 (packed red blood cells), and 78.0 micrograms/1 (plasma). In 62 samples of urine, the selenium level, expressed as micrograms/g creatinine, was 11.4. The mean whole blood selenium concentration was significantly higher in men than women: 104.5 +/- 23.2 vs. 96.9 +/- 21.2 micrograms/1. No differences were found in red blood cells, plasma and urine between male and female subjects. A strong linear correlation was observed between red blood cell and whole blood selenium levels (r = 0.879; p less than 0.001) as well as between selenium levels in whole blood and plasma (r = 0.806; p less than 0.001). A weaker but still significant linear correlation was found between urine and whole blood as well as between urine and plasma selenium concentrations. The relatively low levels of the element in the blood and urine are probably due to its deficiency in the diet.