Selenium in Complicated Pregnancy. A Review.

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.

Selenium and selenium-dependent antioxidants in chronic kidney disease.

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.

The effect of selenium supplementation in the prevention of DNA damage in white blood cells of hemodialyzed patients: a pilot study.

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.

Selenium supplementation to chronic kidney disease patients on hemodialysis does not induce the synthesis of plasma glutathione peroxidase.

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.

Red blood cell and plasma glutathione peroxidase activities and selenium concentration in patients with chronic kidney disease: a review.

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.

Glutathione and glutathione peroxidase activities in blood of patients in early stages following kidney transplantation.

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.

Selenium level in benign and cancerous prostate.

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.

Selenium and glutathione peroxidases in blood of patients with different stages of chronic renal failure.

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.

Selenium concentrations and glutathione peroxidase activities in blood of patients before and after allogenic kidney transplantation.

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.

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 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.

[Reactive oxygen species as an inducing factor of neoplasms of female reproductive organs ]. / Reaktywne formy tlenu jako jeden z czynników rozwoju nowotworów narzadów plciowych kobiet.

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.

Selenium, glutathione and glutathione peroxidases in blood of patients with chronic liver diseases.

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.

[Plasma selenium concentration, glutathione peroxidase and glutathione S-transferase activities in patients with chronic liver diseases]. / Stezenie selenu, aktywnosc peroksydazy glutationowej i transferazy glutationowej w osoczu chorych na przewlekle schorzenia watroby.

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.