Glutathione peroxidase and glutathione S-transferase activity of platelets

A low Se intake in dietetically treated patients with phenylketonuria (PKU) or maple syrup urine disease (MSUD) leads to a marked reduction of the platelet glutathione peroxidase activity (GSHPx). The mean value amounted to 2.0 U/10(11) platelets with t-butyl hydroperoxidase (t-BOOH) (2.2 U/10(11) with H2O2) in patients and 5.8 U/10(11) with t-BOOH (5.4 U/10(11) with H2O2) in the control children. After Se supplementation with yeast rich in Se (dose: 135 micrograms Se/m2) the GSHPx activities rapidly increased. They reached a plateau after 2-3 weeks and remained there during the following 15-20 weeks of supplementation. After the cessation of supplementation there was a slow decrease, the values reached a low plateau after 24 weeks. In addition platelet glutathione S-transferase (GSHTf) was estimated with 1-chloro-2,4-dinitrobenzene. No significant difference between the values in healthy and dietetically treated patients in a low or normal Se state was observed. GSHTf did not exhibit peroxidase activity and did not show a compensatory increase when Se dependent GSHPx activity was low. The patients do not reveal clinical signs of disturbed platelet function. GSHPx may act in platelets via lipoxygenase on the prostaglandin pathway. The physiologic consequence of altered arachidonate metabolism, when GSHPx is deficient in platelets, remains to be elucidated.     

Selenium requirements in patients with inborn errors of amino acid metabolism and selenium deficiency

The diets of 5 patients with phenylketonuria or maple-syrup-urine disease were supplemented with yeast which was rich in selenium. For 120 days the patients received 45 g Se/day to increase the Se content of their diets to 10–12ng Se/Kjoule. Before supplementation the selenium content of serum (5–15 ng/ml) and whole blood (10–27 ng/ml), and the activity of the erythrocyte glutathione peroxidase (0.19–2.69 U₃₇/g Hb), amounted to only 10–20% of normal. The serum selenium content reached normal values within 4 weeks of supplementation, followed by normalisation of the selenium content of whole blood within 4–8 weeks. Restoration of the activity of erythrocyte glutathione peroxidase took 9 to 15 weeks —the red cell life span. There was a significant positive correlation between the selenium content of the erythrocytes and the activity of erythrocyte glutathione peroxidase.With support of Deutsche Forschungsgemeinschaft     

The selenium state of children

The selenium content of serum, whole blood and hair was measured by neutron activation analysis in dietetically treated patients with phenylketonuria (PKU) and maple-syrup-urine disease (MSUD). Follow-up studies showed a decrease of the serum selenium content and the glutathione peroxidase activity of erythrocytes—a selenoenzyme—from normal values at the beginning of the diet to 20% (selenium) and 50% (gluthione peroxidase) of normal within 10–12 weeks of dietary treatment. In 36 patients the serum selenium content was lower at 6.7–28×10^-9 g/ml, independent of the age of the patients (0.5 to 10 years). The selenium content of whole blood was reduced: median=98×10^-9 g/g dry weight; range 75 to 165×10^-9 g/g dry weight (healthy children: median=381×10^-9 g/g dry weight; range 245 to 588×10^-9 g/g dry weight). The selenium content of hair was markedly lower in the patients (median=62×10^-9 g/g; range 13–140×10^-9 g/g) than in healthy children (median=429; range 213 to 720×10^-9 g/g). The mean glutathione peroxidase activity of erythrocytes was reduced to 4.6±0.64 U₃₇/g Hb, in comparison to normal values (mean=8.8±0.88 U₃₇/gHb).With support of the Deutsche Forschungsgemeinschaft     

Effect of selenium supplementation on the distribution of selenium among plasma proteins of a patient with maple syrup urine disease

Selenium (Se) status was studied in a patient with classical maple syrup urine disease (MSUD) receiving Se supplement. The basal plasma Se concentration was 0.06 mol/l increasing to 2.1 mol/l after 40 days of supplementation. When the plasma Se distribution was analysed by gel filtration, a major peak was seen close to the high molecular weight proteins with a second peak in the albumin region. When the Se dose was decreased in a stepwise manner from 50 g/day to 25 g/day and then to 17 g/day plasma Se decreased, but the proportion of plasma Se in the two protein peaks did not change. In a healthy girl not supplemented with Se, the proportion of plasma Se in the albumin region was somewhat lower. In the MSUD patient glutathione peroxidase activity was initially low, and increased ten-fold during Se supplementation. The study indicates that the Se requirement for plasma glutathione peroxidase activity was fulfilled at the lowest dose of Se used and that Se is incorporated into several plasma proteins after supplementation.Abbreviations MSUD maple syrup urine disease - Se selenium     

Effects of a low selenium state in patients with phenylketonuria

Abstract Eighty-seven participants of the German Collaboratory Study for Children with Phenylketonuria (PKU) presented low plasma, whole blood and hair selenium (Se) values, reduced urinary selenium excretion, and decreased plasma and erythrocyte glutathione peroxidase activity in comparison with a healthy reference group (all figures p < 0.001). Aspartate amino transferase and thyroxine (T₄) concentrations in plasma were inversely correlated with the selenium blood values of the PKU children. Somatic measurements showed a negative standard deviation score of body height in the PKU children compared with reference values. Despite the different Se supply, the infants did not present any specific Se deficiency symptoms.     

Blood selenium content and glutathione peroxidase activity in children with cystic fibrosis,coeliac disease,asthma, and epilepsy

Long-term selenium status in children from the North-East of Scotland was estimated using whole blood selenium content (BSe) and glutathione peroxidase activity (BGSH-Px). BSe was significantly lower than the reference range in children with cystic fibrosis, coeliac disease and in older patients with phenylketonuria. Whereas BGSH-Px of all the children with coeliac disease and those with cystic fibrosis aged over 6 years matched the reference range, it was reduced in younger patients with cystic fibrosis and in children with dietetically treated phenylketonuria. No child had clinical features of selenium deficiency. BSe in treated epileptics and asthmatics conformed to the reference range, but BGSH-Px in both groups was increased significantly; this was most evident in those receiving corticosteroid preparations.     

Selenium intake of infants and young children,healthy children and dietetically treated patients with phenylketonuria

In 20 healthy infants and children, 5–20 months old, the Se intake was estimated by analysing food samples by instrumental neutron activation analysis. The intake was calculated by weighing the portions offered and actually consumed. The median Se content of the food amounted to 27 ng/g wet weight (gww) and median daily Se intake to 33.5 g.The Se intake was not equally distributed over the day. About 50% of the daily Se intake was derived from the supper. The main Se sources (41%) for young children were cereal paps. Commercially, available meals (30 ng/g) contained less Se than home-made ones (50 ng/g). In nine dietetically treated patients with phenylketonuria the median Se intake amounted only to 6.9 g/day corresponding to a mean Se content of the diet of 7.9 ng/g. The main Se source in the diet was vegetables (36.3%) and 20% derived from their protein supplements.The Se intake of young children, healthy or dietetically treated, cannot be calculated accurately from tables but must be estimated by measuring the Se content of the local food because cereals and vegetables-the main Se sources-exhibit great regional variations.Abbreviations Se selenium - PKU phenylketonuria - gww gram wet weight     

Increased plasma and erythrocyte selenium concentrations but decreased erythrocyte glutathione peroxidase activity after selenium supplementation in children with Down syndrome

An investigation was made of the activity of glutathione peroxidase (GSH-Px) in erythrocytes and the levels of selenium in plasma and erythrocytes before, during and after selenium supplementation in children with Down syndrome (DS). This subject is of interest since it has been suggested that selenium supplementation could enhance the GSH-Px activity in erythrocytes, probably leading to improved protection against oxygen radicals, which might cause damage by lipid peroxidation, especially in the brain. Forty-eight children with DS were treated with selenium-rich yeast tablets (10 micrograms/kg body weight/day) for 6 months. The supplementation was well tolerated and no side effects were observed. Selenium supplementation resulted in increased concentrations of selenium both in plasma and erythrocytes, but decreased GSH-Px-activity in erythrocytes. Plasma and erythrocyte selenium levels but almost regained the initial values 12 months after termination of the supplementation. Erythrocyte GSH-Px activity, on the other hand, remained reduced and did not return to the presupplementation levels. Until we gain more knowledge about the biological functions of selenium in man and the role of oxygen metabolism in the development of presenile dementia in DS, universal selenium supplementation in DS patients cannot be recommended.     

Potentially life-threatening cardiac dysrhythmia in a child with selenium deficiency and phenylketonuria

Selenium deficiency is a frequent finding in children with phenylketonuria (PKU) receiving dietary treatment. We report the occurrence of episodic ventricular tachycardia in a 9-month-old infant with PKU. Serum selenium (Se), 0.13 mumol/l (normal range 0.28-1.12 mumol/l, mean +/- 2 SD), and whole blood glutathione peroxidase (GSHPX), 16 U/g Hb (normal range 19.5-34.3 U/g Hb, mean +/- 2 SD), were low. Auscultation of cardiac rhythm is recommended during the routine follow-up of young children with PKU. Se deficiency should be considered in the aetiology of a dysrhythmia and corrected with Se supplementation.     

Selenium supplementation in X-linked muscular dystrophy. Effects on erythrocyte and serum selenium and on erythrocyte glutathione peroxidase activity

The selenium concentrations in serum and erythrocytes and the erythrocyte glutathione peroxidase activity were determined in 15 boys with the Duchenne type and in 5 boys with the Becker type of X-linked muscular dystrophy before and during long-term selenium and alpha-tocopherol supplementation and compared with values in unsupplemented controls. The purpose of the treatment was to improve the muscular strength. Twelve of the 20 patients had pretreatment levels of selenium in serum that were within the 95% confidence limit of the unsupplemented control children. The values in 2 patients, both with the Duchenne type of muscular dystrophy, fell below this level. Selenium supplementation in a daily dose of 6 micrograms/kg/day for 6 months caused a substantial rise in both serum and erythrocyte selenium, suggesting suboptimal pretreatment body contents of selenium. The greatest increases in both serum and erythrocyte selenium were observed in subjects with initially low selenium levels. Only in 4 of the 20 patients did the selenium supplementation result in a significant rise in erythrocyte glutathione peroxidase activity. As no sure improvement was noted in muscular strength during this treatment period, the Se dose was increased to 20 micrograms/kg/day. This resulted in a further rise in both serum and erythrocyte selenium, but not in erythrocyte glutathione peroxidase activity.     

Selenium status of New Zealand infants fed either a selenium supplemented or a standard formula

Objective: New Zealand soils are deficient in the essential micronutrient, selenium. New Zealand infants have low selenium levels at birth and experience a further decline if fed cows milk based formula. This study examined the selenium status of infants fed with a new commercially available selenium supplemented formula.
Methodology Forty-four newborn infants, whose mothers wished to formula feed, were randomized in an open controlled trial to be fed a commercially available selenium supplemented cows milk formula (containing 17 μg Se/L) or an unsupplemented formula (containing 4.6 μg Se/L). Cord, 1 and 3 month blood samples were obtained for selenium status (plasma and red cell selenium and glutathione peroxidase) and thyroid function.
Results Mean plasma selenium and glutathione peroxidase values were significantly higher in supplemented than unsupplemented infants at 1 month (unpaired t -tests; P <0.0001 and P = 0.001 respectively) and 3 months ( P <0.0001 and P = 0.0005). Analysis within treatment groups between time points (paired t -tests) showed that selenium supplementation prevented the fall in plasma selenium from birth to 1 month seen in unsupplemented infants and was associated with a rise in levels between 1 and 3 months ( P = 0.002).
Conclusions Supplementing cows milk formula with selenium to replicate the levels found in breast milk is nutritionally sound. Feeding from a few days of age with a formula containing 17 μg Se/L in infants with low selenium status at birth is sufficient to cause a rise to 80% of adult levels at 3 months of age.     

The selenium status of children with phenylketonuria: results of selenium supplementation

The selenium status of children with phenylketonuria on a synthetic low phenylalanine diet was assessed. Correlation between blood selenium and red cell glutathione peroxidase was unsatisfactory (r = 0.65) due to the poor discrimination of red cell glutathione peroxidase with a low selenium diet. No symptoms of deficiency were observed. Supplementation with 50 micrograms per week of selenium as brewers yeast tablets over a period of 6 months significantly increased the blood selenium of the phenylketonuric children. Plasma Vitamin E levels were within normal limits. The supplementation effectively doubled their selenium intake to 15-17 micrograms per day, which is probably sufficient for this group with an adequate Vitamin E status, though considerably lower than the recommended minimum intake of 50 micrograms per day.     

Acute selenium poisoning of a 2-year-old child

After ingestion of an unknown amount of a gun blueing compound containing selenious acid (11 ml from the bottle fluid were missing, equivalent to 2.9 g Se) a 2-year-old girl suffered from continuous hyper-salivation, vomiting, diarrhoea, restlessness and muscle spasm. Blood pressure and pulse rate were increased. Symptomatic treatment was performed by parenteral fluid administration. The plasma Se concentration was increased to 20 times normal 5 h after ingestion. Erythrocyte Se exceeded plasma Se, 24 h after intoxication. Urinary Se excretion decreased parallel to the plasma Se concentration. Ten weeks later, the Se content of hair had risen to 10 times normal. The plasma glutathione peroxidase activity showed only a slight increase during the first 36 h, erythrocyte glutathione peroxidase, catalase and superoxide dismutase activities were not significantly altered. The child fully recovered.     

Influence of age on the selenium status in Belgium and The Netherlands

Plasma selenium concentration and glutathione peroxidase activity in red blood cells were determined in subjects from different age groups. The selenium level (mean +/- SD) found in infancy (0 to 6 months) was 2 +/- 0.6 micrograms/dl, with the lowest value of 1 microgram/dl observed in a 4-month-old infant. These levels were significantly lower (p less than 0.001) than the value of 9.5 +/- 1.1 micrograms/dl found in the adult group and 7.7 +/- 1.3 micrograms/dl found in the group of older children (2 to 15 yr). Younger children (6 to 24 months of age) had intermediate levels of 5 +/- 1.2 micrograms/dl. When the data were plotted on a logarithmic scale as a function of age, the figure shows clearly that the plasma selenium levels increase steadily with age throughout life after an initial drop at 60 to 90 days. There was a satisfactory correlation between the plasma selenium concentration and the enzyme glutathione peroxidase activity in the red blood cells (Spearman's p = 0.45, p less than 0.005). Although very low selenium values were observed, the enzyme glutathione peroxidase activity remained above 10 U/g hemoglobin (with only one exception) in all patients.     

The selenium status of children with phenylketonuria: Results of selenium supplementation

The selenium status of children with phenylketonuria on a synthetic low phenylalanine diet was assessed. Correlation between blood selenium and red cell glutathione peroxidase was unsatisfactory ( r = 0.65) due to the poor discrimination of red cell glutathione peroxidase with a low selenium diet. No symptoms of deficiency were observed. Supplementation with 50 μg per week of selenium as brewers yeast tablets over a period of 6 months significantly increased the blood selenium of the phenylketonuric children. Plasma Vitamin E levels were within normal limits. The supplementation effectively doubled their selenium intake to 15–17 μg per day, which is probably sufficient for this group with an adequate Vitamin E status, though considerably lower than the recommended minimum intake of 50 μg per day.     

Comparison between preterm and full term neonatal cord selenium in correlation to maternal serum selenium levels

Background

Lower concentrations of selenium and glutathione peroxidase activities have been reported in pregnant women. An exposure to a high oxygen concentration at birth, an infection, inflammation, and a deficient antioxidant system make the newborn more susceptible to oxidative stress that can result in bronchopulmonary dysplasia, retinopathy of prematurity, persistent ductus arteriosus, necrotizing enterocolitis, intracranial hemorrhage, and hypoxic ischemic encephalopathy, especially in extremely low-birth-weight infants.

Selenium Supplementation in X-linked Muscular Dystrophy

ABSTRACT. The selenium concentrations in serum and erythrocytes and the erythrocyte glutathione peroxidase activity were determined in 15 boys with the Duchenne type and in 5 boys with the Becker type of X-linked muscular dystrophy before and during long-term selenium and α-tocopherol supplementation and compared with values in unsupplemented controls. The purpose of the treatment was to improve the muscular strength. Twelve of the 20 patients had pretreatment levels of selenium in serum that were within the 95 % confidence limit of the unsupplemented control children. The values in 2 patients, both with the Duchenne type of muscular dystrophy, fell below this level. Selenium supplementation in a daily dose of 6 μg/kg/day for 6 months caused a substantial rise in both serum and erythrocyte selenium, suggesting suboptimal pretreatment body contents of selenium. The greatest increases in both serum and erythrocyte selenium were observed in subjects with initially low selenium levels. Only in 4 of the 20 patients did the selenium supplementation result in a significant rise in erythrocyte glutathione peroxidase activity. As no sure improvement was noted in muscular strength during this treatment period, the Se dose was increased to 20 μg/kg/day. This resulted in a further rise in both serum and erythrocyte selenium, but not in erythrocyte glutathione peroxidase activity.     

Blood selenium concentrations and glutathione peroxidase activity.

Selenium concentrations in children and teenagers without a metabolic disorder eating normal diets (group 1), and young patients with classical phenylketonuria and milder forms of hyperphenylalaninaemia being treated with a diet low in natural protein (group 2) were investigated. There was a strong correlation between blood selenium concentration and age in children in group 1 up to 10 years of age. Blood selenium concentrations and glutathione peroxidase activities were significantly lower in the patients who were receiving diets containing reduced amounts of natural protein, and the differences were more than would be expected for age. When the concentrations of selenium in blood from groups 1 and 2 were compared with glutathione peroxidase activity, a strong association was found when blood selenium concentrations were below 1.26 mumol/l. Reduction in glutathione peroxidase activity may be harmful in the long term, and the addition of selenium to therapeutic diets is recommended.     

Increased Plasma and Erythrocyte Selenium Concentrations but Decreased Erythrocyte Glutathione Peroxidase Activity after Selenium Supplementation in Children with Down Syndrome

ABSTRACT. An investigation was made of the activity of glutathione peroxidase (GSH-Px) in erythrocytes and the levels of selenium in plasma and erythrocytes before, during and after selenium supplementation in children with Down syndrome (DS). This subject is of interest since it has been suggested that selenium supplementation could enhance the GSH-Px activity in erythrocytes, probably leading to unproved protection against oxygen radicals, which might cause damage by lipid peroxidation, especially in the brain. Forty-eight children with DS were treated with selenium-rich yeast tablets (10 μg/kg body weight/day) for 6 months. The supplementation was well tolerated and no side effects were observed. Selenium supplementation resulted in increased concentrations of selenium both in plasma and erythrocytes, but decreased GSH-Px-activity in erythrocytes. Plasma and erythrocyte selenium levels had almost regained the initial values 12 months after termination of the supplementation. Erythrocyte GSH-Px activity, on the other hand, remained reduced and did not return to the presupplementation levels. Until we gain more knowledge about the biological functions of selenium in man and the role of oxygen metabolism in the development of presenile dementia in DS, universal selenium supplementation in DS patients cannot be recommended.