Sodium Selenite Supplementation Research Articles

Effect of Sodium Selenite Supplementation on Glucose Intolerance and Pancreatic Oxidative Stress in Type 2 Diabetic Mice under Different Selenium Status

The objective of this study was to investigate the effect of various selenium (Se) status on glucose intolerance and pancreatic oxidative stress or the defense systems in Nagoya-Shibata-Yasuda (NSY) mice as the animal model for type 2 diabetes mellitus. To let the mice become Se-insufficient to Se-sufficient conditions, the NSY mice were given normal or Se-deficient diet with 0–7.0 mg/l Na2SeO3-containing drinking water for 6, 8 or 12 weeks. In NSY mice ingested normal diet, levels of blood glucose and plasma insulin after intraperitoneal glucose tolerance test (IPGTT) were not significantly affected by Na2SeO3-supplementation. In Se-deficient diet-treatment groups, however, the supplementation resulted in the decrease of blood glucose and the increase of plasma insulin after IPGTT. Although glutathione peroxidase (GPX) 1 activity in pancreas of the NSY mice ingested Se-deficient diet was augmente db y Na 2SeO3-supplementation, pancreatic glutathione was depressed by the supplementation, accompanying by the increase of 2-thiobarbituric acid-reactiv es ubstances. These results indicated that although the supplemented Na2SeO3 may not protect against oxidative stress in the pancreas of NSY mice under Se-insufficient condition, the Se compound improved glucose intolerance of the mice.

Selenium supplementation improves antioxidant capacity in vitro and in vivo in patients with coronary artery disease: The SElenium Therapy in Coronary Artery disease Patients (SETCAP) Study

Selenium is a central determinant of antioxidative glutathione peroxidase 1 (GPx-1) expression and activity. The relevance of selenium supplementation on GPx-1 in coronary artery disease (CAD) needs to be established. We assessed the effect of selenium supplementation on GPx-1 in cell culture and on endothelial function in a prospective clinical trial. Human coronary artery endothelial cells were incubated with 5.78 to 578 nmol/L sodium selenite, Se-methyl-selenocysteine hydrochloride, or seleno-l-methionine. Glutathione peroxidase 1 mRNA and protein expression and activity were measured. Coronary artery disease patients (n = 465) with impaired endothelial function (flow-mediated dilation [FMD] <8%) were randomly assigned to receive 200 or 500 microg sodium selenite daily or matching placebo during a 12-week period. We tested the effect on red blood cell GPx-1 activity and brachial artery FMD. Furthermore, differences in biomarkers of oxidative stress and inflammation were measured. Sodium selenite and Se-methyl-selenocysteine hydrochloride increased GPx-1 protein and activity in a dose-dependent manner (P < .0001). The intention-to-treat groups comprised 433 CAD patients. Glutathione peroxidase 1 activity increased from 37.0 U/gHb (31.3-41.7) to 41.1 U/gHb (35.2-48.4) (P < .0001) in the 200 microg and from 38.1 U/gHb (33.2-43.8) to 42.6 U/gHb (35.0-49.1) (P < .0001) in the 500 microg sodium selenite group treated for 12-weeks. No relevant changes were observed for FMD or biomarkers of oxidative stress and inflammation. Sodium selenite supplementation increases GPx-1 activity in endothelial cells and in CAD patients. Future studies have to demonstrate whether long-term CAD outcome can be improved.

Protective effect of sodium selenite and zinc sulfate on intensive swimming-induced testicular gamatogenic and steroidogenic disorders in mature male rats

To investigate the ameliorative potential of sodium selenite and zinc sulfate on intensive-swimming-induced testicular disorders, 48 Wistar male rats (age, 4 months; mass, 146.2 +/- 3.6 g) were randomly divided into 4 groups: the unexercised-control group (n = 12); the exercised group (n = 12); the control supplemented group (n = 12); and the exercised supplemented group (n = 12). For 10 weeks, the exercised rats underwent a protocol that consisted of 4 h.d-1 swimming, for 6 d.week-1; the control rats did not exercise. For 10 weeks, both the supplemented groups received an oral daily dose of a combination of sodium selenite and zinc sulfate (6 and 3 mg.kg body mass-1, respectively). After 10 weeks, a significant reduction (p < 0.05) was seen in rats in the exercised group, compared with rats in both control groups, in paired testicular masses; in epididymal sperm count; in testicular Delta5, 3beta-hydroxysteroid dehydrogenase (HSD) and 17beta-HSD; in plasma levels of testosterone, luteinizing hormone, follicle-stimulating hormone, and prolactin; in the numbers of preleptotine spermatocytes, midpachytene spermatocytes, and stage 7 spermatids of the stage VII seminiferous epithelium cycle; and in fertility performance. As well, a significant increase (p < 0.05) was seen in the exercised group, compared with both control groups, in plasma corticosterone levels and in testicular content of malondialdehyde and catalase activity. At the same time, there was a significant reduction (p < 0.05) in the exercised group, compared with both control groups, in plasma concentrations of zinc and selenium; in the testicular content of glutathione (GSH), the glutathione and glutathione disulphide (GSSG) ratio, ascorbic acid, and alpha-tocopherol; and in testicular activities of superoxide dismutase, glutathione-peroxidase, and glutathione-S-transferase in the testes. No significant changes were seen in the number of spermatogonia-A from the stage VII seminiferous epithelium cycle or the testicular content of GSSG among the groups. Sodium selenite and zinc sulfate supplementation significantly protected against exercise-induced testicular gamatogenic and spermatogenic disorders, prevented testicular oxidative stress, and increased antioxidant status. It can be concluded that intensive-swimming-induced oxidative stress causes dysfunctions in the male reproductive system, which can be protected by the coadministration of sodium selenite and zinc sulfate.

Effects of dietary supplementation with selenium enriched yeast or sodium selenite on selenium tissue distribution and meat quality in lambs

The objective was to determine the concentration of total selenium (Se) and the proportion of total Se comprised as selenomethionine (SeMet) and selenocysteine (SeCys), as well as meat quality in terms of oxidative stability in post-mortem tissues of lambs offered diets with an increasing dose rate of selenized enriched yeast (SY), or sodium selenite (SS). Fifty lambs were offered, for a period of 112 d, a total mixed ration which had either been supplemented with SY (0, 0.11, 0.21 or 0.31 mg/kg DM to give total Se contents of 0.19, 0.3, 0.4 and 0.5 mg Se/kg DM for treatments T1, T2, T3 and T4, respectively) or SS (0.11 mg/kg DM to give 0.3 mg Se/kg DM total Se [T5]). At enrolment and at 28, 56, 84 and 112 d following enrolment, blood samples were taken for Se and Se species determination, as well as glutathione peroxidase (GSH-Px) activity. At the end of the study lambs were euthanased and samples of heart, liver, kidney, and skeletal muscle were retained for Se and Se species determination. Tissue GSH-Px activity and thiobarbituric acid reactive substances (TBARS) were determined in Longissimus Thoracis. The incorporation into the diet of ascending concentrations of Se as SY increased whole blood total Se and the proportion of total Se comprised as SeMet, and erythrocyte GSH-Px activity. Comparable doses of SS supplementation did not result in significant differences between these parameters. With the exception of kidney tissue, all other tissues showed a dose dependant response to increasing concentrations of dietary SY, such that total Se and SeMet increased. Selenium content of Psoas Major was higher in animals fed SY when compared to a similar dose of SS, indicating improvements in Se availability and retention. There were no significant treatment effects on meat quality assessments GHS-Px and TBARS, reflecting the lack of difference in the proportion of total Se that was comprised as SeCys. However, oxidative stability improved marginally with ascending tissue Se content, providing an indication of a linear dose response whereby TBARS improved with ascending SY inclusion.

Effect of dietary selenium sources on growth performance, breast muscle selenium, glutathione peroxidase activity and oxidative stability in broilers

This study examined the effects of supplementation of dietary sodium selenite and sodium enriched alga &lt;I&gt;Chlorella&lt;/I&gt; on growth performance, selenium concentration in breast meat and excreta, activity of glutathione peroxidase in meat, and oxidative stability of meat in broilers. Sexed broiler cockerels Ross 308 were allotted to 3 dietary treatments, each comprising 100 chickens. The basal diet was supplemented with 0 (control) or 0.3 mg/kg Se from sodium selenite (SS) or Se-&lt;I&gt;Chlorella&lt;/I&gt; (SCH). Dietary supplementation with SCH increased (&lt;I&gt;P&lt;/I&gt; &lt; 0.05) body weight. The breast muscle Se concentration was increased (&lt;I&gt;P&lt;/I&gt; &lt; 0.05) by SCH (0.70 mg/kg DM; 0.36 mg/kg DM in control) supplementation, but not (&lt;I&gt;P&lt;/I&gt; &gt; 0.05) by SS (0.49 mg/kg DM) supplementation. The concentration of Se in excreta was highest in the SS group. The activity of GSH-Px in breast meat was significant &lt;I&gt;P&lt;/I&gt; &lt; 0.05) in all treatments (0.16 U/g in control, 0.30 U/g in SS and 0.23 U/g in SCH group). The inclusion of SCH in the diet enhanced the oxidative stability of meat expressed as reduced malondialdehyde (MDA) values in breast meat after 0; 3 and 5 days storage in refrigerator at 3 to 5°C.

Differential liquid phase proteomic analysis of the effect of selenium supplementation in LNCaP cells

The effect of 100 nM sodium selenite supplementation was studied on LNCaP cells by a proteomic approach, on ProteomeLab™ PF 2D platform. Proteins were separated by liquid phase bi-dimensional chromatography and analyzed by pair-wise alignment of peaks to detect those differentially expressed. Differential expression threshold was set at a twice difference level and proteins matching this criterion were identified by MALDI-TOF and confirmed by ESI-ion trap MS/MS. Not all differentially expressed proteins found by PF 2D could be identified by MS analysis, the sensitivity of which emerging as the limiting factor. Thus, only the most abundant proteins, differently expressed following selenium supplementation, were identified. We positively showed an increase of expression of thioredoxin reductase 1, enolase 1, phosphoglycerate mutase 1, glyceraldehyde-3-phosphate dehydrogenase, heterogeneous nuclear ribonucleoprotein A2/B1, isoform A2, Ras-GTPase-activating protein SH3-domain-binding protein and Keratin 18 and a decrease of expression of peroxiredoxin 1 and heat shock protein 70, protein 8, isoform 1. Results are consistent, at least in part, with the less oxidant environment brought about by the synthesis of Se-dependent peroxidases, keeping low the steady-state concentration of hydrogen peroxide.

Selenium supplementation increases liver MnSOD expression: Molecular mechanism for hepato-protection

Selenium is recognized as essential in animal and human nutrition. Several hypotheses have been advanced for its biological activity. The aim of this study was to investigate the in vivo effect of selenium on rat liver manganese superoxide dismutase (MnSOD), a key antioxidant enzyme, under naïve and inflammatory conditions. Rats received sodium selenite supplementation and LPS injection. Whole-liver samples, isolated hepatocytes, Kupffer cells and blood samples were subjected to protein, RNA and biochemical analysis. Liver enrichment with selenium increased whole-liver MnSOD levels due to an increase in MnSOD transcription in hepatocytes. This was due to an increase in the ratio of specificity protein 1 to activating enhancer binding protein 2 DNA-binding activity. The inflammatory stimulus further elevated MnSOD levels in the whole-liver that was abrogated in sodium selenite supplementation due to reduced transcription of MnSOD in Kupffer cells. Moreover, selenium enrichment decreased Kupffer cells IL-6 transcription in LPS-injected animals. Anti-inflammatory activity of selenium was demonstrated by normalized blood levels of ALT and IL-6 in LPS-injected animals. In conclusion, selenium up-regulates hepatocytes MnSOD expression, probably improving their anti-oxidant defense, while decreasing MnSOD and IL-6 transcription in Kupffer cells in the presence of inflammatory stimuli, attenuating their inflammatory response. This selective mechanism may explain the anti-inflammatory and hepato-protective effect of selenium.

Protection of doxorubicin-induced DNA damage by sodium selenite and selenomethionine in Wistar rats

The importance of selenium in human nutrition is well recognized. It is an important micronutrient involved in antioxidant defense and is of fundamental importance in the maintenance of genomic stability. However, questions relating to the appropriate chemical form of selenium used for supplementation and its beneficial dose is still being debated. Therefore, the present study investigated the ability of 2 selenium compounds-sodium selenite (SS) and selenomethionine (SM)-to protect DNA against the damage induced by doxorubicin (DXR). Wistar rats were supplemented orally for 10 consecutive days with SS or SM (1 and 2 mg/kg bw); 24 hours before euthanasia a single dose of DXR (90 mg/kg bw) was injected intraperitoneally. DNA lesions were assessed by the comet assay and micronucleus test; the concentrations of thiobarbituric acid reactive substances, vitamin E, and reduced glutathione were determined by using liver homogenates. The results obtained showed that SS and SM prevented the induction of DNA damage by DXR. It was also observed that these 2 selenium compounds increased the hepatic concentration of glutathione, maintained the thiobarbituric acid reactive substances, and allowed for the maintenance of hepatic concentrations of vitamin E even after DXR treatment, confirming the antioxidant properties of selenium compounds. Sodium selenite and SM supplementation exhibited very similar patterns of protection. In conclusion, SS and SM supplementation was effective in protecting DNA against DXR-induced DNA damage in Wistar rats, probably because of their antioxidant properties.

Selenium improves the developmental ability and reduces the apoptosis in porcine parthenotes

Selenium is an essential trace element in conventional tissue culture media to guarantee adequate biosynthesis of selenoprotein in cellular antioxidant system to protect the cells from oxidative damage and apoptosis. This study investigated the effect of selenium, in the form of sodium selenite (SS), on developmental ability and quality of in vitro produced porcine parthenotes. For this, parthenogenetic presumptive diploid zygotes were produced by electroactivation and cultured in the absence or presence of SS at different concentrations (0, 2.5, 25, 250 ng/ml) in a serum-free defined culture medium supplemented with polyvinyl alcohol (PVA) or bovine serum albumin (BSA). Results showed that, development rate of 2-4 cell stage parthenotes to blastocyst and their cell number was increased while TUNEL index was decreased, in a dose-dependent manner, when SS was supplemented to NCSU23 + PVA. Interestingly, the blastocyst rate and their quality approached to those cultured in NCSU23 + BSA (P < 0.05), thereby suggesting PVA + 25 ng/ml SS to be a partial replacement of BSA. In the presence of PVA, supplementation of SS at a concentration of 25 ng/ml did not improve the cleavage rate of in vitro matured oocytes but there was significant improvement in the blastocyst rate (45.4 +/- 8.8% vs. 12.7 +/- 4.8%), total nuclei number (42.1 +/- 3.5 vs. 31.3 +/- 2.9) and inner cell mass (ICM) rate (29.4 +/- 1.5% vs. 21.3 +/- 1.2%) and decrease in TUNEL index (5.6 +/- 0.5 vs. 12.9 +/- 1.3) compared to nonsupplemented controls. The SS supplementation also decreased the BAX:BCL-xL transcript ratio, increased the expression of ERK1/2 and glutathione peroxidase (GPX) and reduced the level of Caspase 3 proteins (P < 0.05). These data thus suggest that SS improves the development rate and quality of porcine parthenotes by preventing oxidative damage and apoptosis.

Effects of Spent Composts of Selenium-enriched Mushroom and Sodium Selenite on Plasma Glutathione Peroxidase Activity and Selenium Deposition in Finishing Hanwoo Steers

Effects of spent composts of selenium-enriched mushroom (Se-SMC) on plasma glutathione peroxidase (GSH-Px) activity and selenium (Se) deposition in finishing Hanwoo (Bos taurus coreanae) steers were investigated. Twenty-five Hanwoo steers (average body weight = 613 kg, average age = 22 months) were allotted to treatments in five groups of five steers per pen for 12 weeks preceding slaughter. Treatments were SMC alone (CON; 0.1 ppm Se), 0.3 ppm (0.3 Se-SMC), 0.6 ppm (0.6 Se-SMC), 0.9 ppm (0.9 Se- SMC), and 0.9 ppm (sodium selenite; SENI) Se. During the experimental period, blood samples were taken to analyze Se concentrations and GSH-Px activities. Muscle and liver samples were collected for analyses of Se contents after slaughter. Dry matter intake and body weight gain were not affected by Se-SMC or sodium selenite supplementation. Selenium concentration in the whole blood and GSH-Px activity in plasma were linearly increased (p<0.01) with increasing levels of Se-SMC. The whole blood Se concentration of SENI treatment was significantly higher (p<0.05) than that of CON treatment from 4 weeks, whereas there was no significant difference in GSH-Px activities between both treatments at 8 and 12 weeks. Selenium content in the hind leg and liver increased linearly (p<0.05) with increasing levels of Se-SMC, but those of SENI treatments were not significantly different from CON treatments. These results suggested that Se in the Se-SMC was highly bioavailable to blood and tissues of ruminants, especially compared with Se in the sodium selenite. Therefore, Se-SMC might be used not only as an inexpensive way of providing Se for ruminants but also as another way of

Practicalities of selenium supplementation in critically ill patients

To review the reason for and clinical effects of selenium supplementation in critically ill patients. Selenium-dependent enzymes and selenoprotein P regulate immune and endothelial cell function. Obviously not the anorganic compounds of selenium but the activity of selenium-dependent enzymes is the most important factor modulating the immune system and the clinical outcome of patients. Despite low selenium levels in severely ill patients and low glutathione peroxidase activity associated with the extent of multiorgan dysfunction, only a few trials have investigated the effect of selenium supplementation on clinical outcome. A metaanalysis did not reveal a statistically significant survival rate with selenium supplementation, but suggested a dose-dependent trend. The recently completed multicentre trial on high-dose selenium supplementation in septic patients also did not reveal a significant overall reduction in mortality. The available evidence suggests that selenoproteins play an important role in the immunomodulation of critically ill patients and a sodium selenite supplementation upregulates these selenoenzymes. The intervention trials with sodium selenite performed to date are small and therefore only a tendency in reduction of morbidity and mortality could be demonstrated. Larger trials are necessary to show the supposed benefits and risks of selenite supplementation in critically ill patients.

Effect of sodium selenite supplementation on the levels of Prostacyclin I 2 and Thromboxane A 2 in human

Selenium is an essential trace element in human health [1,2], an important part of the antioxidant enzymes that protect cells against the effects of free radicals that are produced during the normal oxygen metabolism. The body has developed defenses, such as antioxidants, to control the levels of free radicals, which can damage cells and contribute to the development of some chronic diseases. Several epidemiological studies have shown that serum selenium levels were associated

Effect of dietary co-administration of sodium selenite on sodium arsenite-induced ovarian and uterine disorders in mature albino rats.

The subchronic treatment of mature female Wistar-strain albino rats in diestrous phase with sodium arsenite at a dose of 0.4 ppm/100 g body weight/rat/day via drinking water for period of 28 days (seven estrous cycles) caused a significant reduction in the plasma levels of leutinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol along with a significant decrease in ovarian activities of delta five, 3 beta-hydroxysteroid dehydrogenase (Delta5,3beta-HSD), and 17 beta-hydroxysteroid dehydrogenase (17beta-HSD) followed by a reduction in ovarian and uterine peroxidase activities. A significant weight loss of the ovary and uterus was also observed after this treatment, along with a prolonged diestrous phase and a high accumulation of arsenic in the plasma and these organs. Moreover, sodium arsenite was also responsible for ovarian follicular and uterine cell degeneration characterized by a high number of regressing follicles and a reduction in the uterine luminal diameter, respectively, in comparison with the controls. A dietary supplementation of sodium selenite at the dose of 0.6 mg/100 g body weight/rat/day for a period of 28 days along with arsenic treatment minimized the gonadal weight loss significantly and increased the activities of the ovarian steroidogenic enzymes as well as the ovarian and uterine peroxidase at the control level. Selenium was also able to increase the plasma levels of LH, FSH, and estradiol toward the control level. Vaginal smears showed normal estrous cyclicity in sodium selenite-supplemented arsenic-treated rats along with lower arsenic levels in the plasma and gonadal tissue in comparison with arsenic-only-treated rats. Histological sections of ovary and uterine tissues in the control and experimental groups confirmed that sodium selenite supplementation was able to prevent arsenic-induced histopathological changes in the ovary and uterus. Plasma levels of norepinephrine and dopamine in the midbrain and diencephalon decreased significantly, whereas the serotonin level was increased significantly after 28 days of sodium arsenite treatment. All of these parameters were, in most cases, unchanged from the control level when sodium selenite was co-administered with sodium arsenite. Arsenic intoxication was also associated with increased liver weight and elevation in the activities of hepatic and renal acid phosphatase, alkaline phosphatase, and transaminases, but selenium co-administration was not able to change these toxic effects of arsenic. The results of our experiments indicate the significant protective action of sodium selenite on arsenic-induced toxicity in the female reproductive system, while there was no significant protective effect of selenium on arsenic-induced toxicity in other organs.

Selenium supplementation can protect cultured rat cardiomyocytes from hypoxia/reoxygenation damage.

The possibility of enhancing glutathione peroxidase (GPx) activity and cytosolic total antioxidant activity (TAA) in normoxia and hypoxia/reoxygenation (H/R) by the supplementation of different concentrations of sodium selenite (SS) or selenomethionine (SM) was investigated in cultured rat cardiomyocytes. To assess the entity of oxidative stress due to H/R, levels of conjugated dienes containing lipids were determined. In normoxia, GPx activity and TAA increased in parallel with the increase in SS and SM supplementation. H/R did not influence GPx activity but lowered TAA; both SS and SM supplementations were effective in increasing GPx activity, the most effective concentration being 1 microM. At this SS and SM concentration, TAA returned to a normoxic value. Conjugated diene production, increased by H/R, was reduced by SS and SM supplementation, the 1 microM concentration appearing to be the most effective one. According to these data Se supplementation represents another possibility to counteract oxidative damage in the myocardium.

Inorganic selenite supplementation and protection against hyperoxic injury in neonates.

This study was designed to determine if oral sodium selenite supplementation to Se-depleted rat pups furnishes protection against hyperoxic lung injury. Twelve female rats were bred and fed a Se-deficient (0.04 ppm Se) diet during pregnancy and lactation. Pups were supplemented either with 0 or 3.2 ng Se/g body weight daily from days 2 to 7. On day 4, two litters were mixed, with half of the pooled litter assigned to an air environment and the other half to an oxygen environment. Dams cross-fostered pups for 4 d. Selenite supplementation increased pup plasma and liver selenium concentration and the liver activity of glutathione peroxidase (GPx). However, lung GPx activity was more affected by oxygen exposure than selenite supplementation. While oral Se supplementation of the pups showed a tendency for decreased incidence of lung injury with oxygen exposure, this apparent effect was not statistically significant. Selenium-supplemented pups also showed a trend toward larger internal surface area and lung volume than selenium-depleted pups. These data indicate that early postnatal selenium repletion via direct oral selenite supplementation may be beneficial to rat pups against hyperoxic lung injury.

Sodium selenite, dietary micronutrient, prevents the lymphocyte DNA damage induced by N-nitrosodiethylamine and phenobarbital promoted experimental hepatocarcinogenesis.

Selenium (Se), a micronutrient, has a long history in chemoprevention of mammary and colon cancers in rodent models. Se is a current clinical trial, having shown promise in prevention of prostate and other human cancers. The mechanisms involved in the in vivo anti-carcinogenic activity of Se remain to be elucidated. In the present study, we examined the effect of sodium selenite supplementation in lymphocytes, obtained from hepatoma bearing rats on DNA damage in correlation with oxidative stress. In addition, this study examined the supplementation of Se at 4-ppm levels in the form of sodium selenite either before initiation or during initiation and/or promotion phase's increases lymphocyte Se concentrations. This in turn improves lymphocyte resistance to oxidative stress and protection against the lymphocytes DNA damage. Supplementation of Se increased lymphocyte Se concentration and reduced lymphocytes DNA damage as determined by single cell gel electrophoresis. The enzymatic antioxidants such as superoxide dismutase, glutathione peroxidase, and catalase were found to be decreased while the thiobarbituric acid reactive substances level was increased in the lymphocytes of hepatoma bearing rats. Furthermore, the reactive oxygen species such as superoxide radicals and hydroxyl radicals were also found to be high in lymphocytes. Our present results explain the understanding of unique association between anti-peroxidative effect of Se and ultimately the capability of Se to prevent cancer.

Interferon/antioxidant combination therapy for chronic hepatitis C—a controlled pilot trial

The effects of two forms of antioxidative co-therapy were analyzed in 24 interferon-alpha (IFN)-naive patients with chronic hepatitis C who were randomized to either receive IFN monotherapy (3×4.5 million units IFN-α 2a per week), (group A), or IFN and N-acetylcysteine ( N-acetylcysteine (NAC) 1.800 mg/day) plus sodium selenite (400 μg/day) supplementation (group B), or treatment as in group B plus vitamin E (544 IU/day) (group C), over 24 weeks. Changes in histology, normalization of ALT, reduction of viral RNA, serum levels of glutathione, selenium, vitamin E, erythrocyte glutathione peroxidase, trolox equivalent antioxidative capacity (TEAC), thiobarbituric acid reactive substances (TBARS) and protein carbonyl groups were measured. Low baseline TEAC and elevated TBARS indicated increased oxidative stress before therapy, which was not affected by antioxidant supplementation. At the end of treatment complete responses were found in 3/8, 2/8 and 6/8 patients in groups A, B and C, respectively, but liver histology had not significantly improved. Vitamin E treated patients had a 2.4 greater chance (95% CI: 1.05–5.5) of obtaining a complete response and had significantly greater reduction in viral load ( P=0.028) than patients without vitamin E. Relapses, i.e. re-appearance of detectable hepatitis C virus (HCV) RNA and/or re-elevation of ALT-activity occurred in 7 out of the 11 responders within 6 months after termination of therapy (group A: 2/3, group B: 1/2 and group C: 4/6). Thus, no overall beneficial effect of antioxidant/IFN therapy was detected. However, the apparent trend towards a more favorable outcome with vitamin E supplementation warrants to further study this substance as an adjuvant to IFN therapy in chronic hepatitis C.

Reversal of selenium and zinc deficiencies in chronic hemodialysis patients by intravenous sodium selenite and zinc gluconate supplementation. Time-course of glutathione peroxidase repletion and lipid peroxidation decrease.

In six chronic dialyzed uremic patients, an intravenous sodium selenite (Se 50 micrograms during 5 wk and then 100 micrograms) and zinc gluconate (Zn 5 mg) supplementation was performed during 20 wk at each dialysis session three times weekly. Before supplementation, plasma Se and Zn, plasma and erythrocytes (RBC) antioxidant metallo-enzymes glutathione peroxidase (GPX), and superoxide dismutase (SOD) were significantly decreased, whereas lipid peroxidation (as thiobarbituric acid reactants TBARs) was increased. To obtain a significative change in plasma selenium, we had to use an Se dose of 100 micrograms/dialysis session. Then, treatment-increased plasma Se (from 0.58 +/- 0.09 to 0.89 +/- 0.16 mumol/L) led to a repletion of RBC-GPX (from 29.6 +/- 6 to 43 +/- 5.8 U/g Hb) and increased plasma GPX levels (from 62 +/- 13 to 151 +/- 43 U/L). Plasma Zn and RBC-SOD did not vary significantly. The change of TBARs was not observed between wk 1 and 4. They decreased significantly between wk 4 (4.80 +/- 0.21 mumol/L) and wk 20 (4.16 +/- 0.26 mumol/L). We noted a low correlation between TBARs and plasma GPX. A strong correlation was observed between Se and plasma GPX. The reversal of Se deficiencies should reduce oxidative damage observed in these patients.

Selenium, glutathione peroxidase (GSH-Px) and lipid peroxidation products before and after selenium supplementation

Treated phenylketonuric (PKU) children are at risk of selenium deficiency. We have studied 15 treated PKU children and 30 control children. We observed significantly lower ( P < 0.0005) plasma and erythrocyte selenium, as well as significantly lower ( P < 0.0005) plasma and erythrocyte glutathione peroxidase activities (GSH-Px) in PKU children than in controls. The lipid peroxidation products, evaluated as plasma malonaldialdehyde (MDA), was higher ( P < 0.0005) in PKU children than in controls. Specific oral sodium selenite supplementation (Selenium: 0.13 μmol/kg/day) resulted in a rapid increase of plasma selenium and GSH-Px activity, and after 10 days and 1 month respectively significant difference is no longer observed between PKU children and controls values. Statistically significant differences in erythrocyte selenium, erythrocyte GSH-Px activity and plasma MDA between PKU and control children disappear after respectively 2 months, 4 months and 6 months of selenium supplementation.

Effects of dietary sodium selenite supplementation on salicylate-induced embryo- and fetotoxicity in the rat

The effects of dietary supplementation with sodium selenite (3.0 or 4.5 ppm Se) for 8 weeks prior to and throughout gestation on sodium salicylate induced embryo- and fetotoxicity (resorptions, fetal deaths, malformations, fetal weight reduction) have been studied in the rat. Salicylate was administered either as daily intragastric bolus doses of 250 mg/kg on gestation days 6—13 (maternal peak and trough salicylate levels of 222—120 μg/ml whole-blood) or via constant rate intravenous infusion of 150 mg/kg/day on the same gestation days via implanted osmotic minipumps (stable average maternal blood salicylate level of 120 μg/ml = human antirheumatic concentration). Both gavage and infusion of salicylate resulted in an increase of resorptions and fetal deaths as well as a decrease of fetal body weights. Gavage with salicylate also produced about 50% malformed fetuses. Selenite did not protect against the embryotoxic effects of salicylate administered as intragastric bolus doses. However, selenite was found to significantly increase fetal survival rate in the infusion experiment, although it did not counteract the decrease of fetal body weight. In animals fed selenite only, no negative effects on fetal body development were noted. The protective effect of selenite against salicylate induced embryotoxicity is difficult to explain, since very little is known about the mechanisms of salicylate embryotoxicity and the biological effects of selenium. However, an interaction between selenium, via glutathione peroxidase, and salicylate at the level of prostaglandin synthesis could be possible.