Bronisław A. Zachara

Tissue level, distribution, and total body selenium content in healthy and diseased humans in Poland.

Abstract 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).

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.

Blood selenium and glutathione peroxidases in miscarriage

Objective To investigate the selenium glutathione and glutathione peroxidase (glutathione‐Px) levels in blood in women who experience miscarriage.

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 GSH-Px 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 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 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.

Selenium, glutathione peroxidases, and some other antioxidant parameters in blood of patients with chronic renal failure

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.

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.

Effect of erythropoietin therapy and selenium supplementation on selected antioxidant parameters in blood of uremic patients on long-term hemodialysis.

BACKGROUND The kidney accumulates the highest level of selenium (Se) in the organism and is the major source of plasma glutathione peroxidase (GSH-Px). Se, as an integral part of the active site of GSH-Px, plays an important role in protecting cell membranes from oxidative damage. Decreased blood Se levels and GSH-Px activity are common in chronic renal failure (CRF) patients. Our study was an effort to evaluate the effect of erythropoietin (EPO) therapy and Se supplementation for CRF patients undergoing regular hemodialysis (HD) on blood Se, red cell glutathione (GSH), and blood lipid peroxidation product levels, and on blood activity levels of GSH-Px and blood superoxide dismutase (SOD). MATERIAL/METHODS Our subjects were divided into three groups: I - CRF patients on regular HD and EPO, II - HD patients receiving EPO and Se, and III - healthy controls. Se levels, SOD and GSH-Px activities were measured spectrofluorometrically, the GSH level by Beutlers colorimetric method, and lipid peroxidation products using TBARS. RESULTS EPO therapy with Se supplementation significantly increased whole blood and plasma Se in HD patients, and raised red cell GSH-Px activity, but plasma GSH-Px activity, plasma superoxide dismutase, and plasma and red cell TBARS did not respond to Se supplementation. EPO alone showed no effect on these parameters. CONCLUSIONS Treatment with EPO and supplementation with Se significantly increased the element concentration in whole blood and plasma, and GSH-Px activity in red cells. Plasma GSH-Px activity did not respond to Se.

Decreased plasma glutathione peroxidase activity in uraemic patients.

Accessible online at: www.karger.com/journals/nef Dear Sir, We read with great interest the paper by Roxborough et al. [1] on the reduction of the glutathione peroxidase (GSH-Px) activity in haemodialysis (HD) patients. The authors noted that in serum of patients with endstage chronic renal failure (CRF), the GSHPx activity was 2.65 times lower when compared to controls (106 vs. 281 U/l; p ! 0.001). Following HD, the GSH-Px activity rose by 38%, although remained below control values. We studied some antioxidant parameters in blood of patients in different stages of CRF. Several groups of patients were investigated: nondialyzed patients and several groups of patients on long-term regular HD: (1) supplemented with baker’s yeast (placebo), (2) supplemented with selenium (Se) in the form of Se-rich yeast (Y-Se; 300 Ìg Se given orally three times a week), (3) treated with erythropoietin at doses of 2,000 U three times a week, and (4) supplemented with YSe and erythropoietin (doses as above). Blood samples were drawn into heparinized vacutainer tubes, and plasma was removed by centrifugation. The plasma Se concentration was assayed fluorometrically [2], and the plasma GSH-Px activity was measured spectrophotometrically by the method of Paglia and Valentine [3] with t-butyl hydroperoxide as substrate. The results obtained were compared with healthy subjects (control group). In all groups of patients, at the beginning of the study, the plasma GSH-Px activity was 1.8 to 2.1 times lower (p ! 0.001) as compared with the control group. The plasma Se levels in nondialyzed and in dialyzed patients before HD, taking the group together (n = 44), were significantly lower (p ! 0.001 and p ! 0.05, respectively) than in healthy subjects. The patients, methods of treatment and plasma Se levels, and plasma GSH-Px activities obtained are shown in table 1. In two groups of HD patients who were regularly supplied with Se, 3 months after supplementation the Se concentration in plasma increased significantly (p ! 0.001), but the GSH-Px activity did not

Glutathione peroxidase activity, selenium, and lipid peroxide concentrations in blood from a healthy Polish population : I. Maternal and cord blood.

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.