Effects of long-term selenium yeast supplementation on selenium status studied in the rat

To investigate the selenium status during long-term dietary supply of selenium yeast, 30-day-old male rats were fed for 379 days a methionine-adequate low-selenium diet supplemented with 0.2 mg Se/kg (selenium-adequate diet) or 1.5 mg Se/kg (high-selenium diet) in the form of selenium yeast that contained 60% of the element as l-selenomethionine. Their selenium load was determined at several intervals by neutron activation analysis of the selenium concentrations in the main selenium body pools, skeletal muscle and liver. After 64 days the tissue selenium concentrations plateaued in both groups and then stayed at that level. Compared with the selenium-adequate group, elevated tissue selenium concentrations were found in the high-selenium group, but the increase by a factor of 3.5 in the muscle and by a factor of 2.3 in the liver was smaller than the 7.5-fold increase in the selenium intake. In the selenium-adequate group about 50% of the muscle selenium and 30% of the liver selenium and in the high-selenium group about 85% of the muscle selenium and 70% of the liver selenium were estimated to be present in non-selenoprotein forms. During selenium depletion the liver glutathione peroxidase activity in the high-selenium group remained unaffected for 4 weeks and then decreased more slowly than that in the selenium-adequate group. From these results it can be concluded that selenium incorporated from the selenium yeast diet into non-selenoprotein forms can serve as an endogenous selenium source to maintain selenoprotein levels in periods of insufficient selenium supply.     

Effects of dietary selenium supplementation on tissue selenium distribution and glutathione peroxidase activity in Chinese Ring Necked Pheasants

The objective of this study was to determine the concentration of total selenium (Se) and the proportions of total Se comprised as selenomethionine (SeMet) and selenocysteine (SeCys) in the postmortem tissues of female pheasants (Phasianus Colchicus Torquator) offered diets that contained graded additions of selenised-enriched yeast (SY) or a single comparative dose of sodium selenite (SS). Thiobarbituric acid reactive substances (TBARS) and tissue glutathione peroxidase (GSH-Px) activity of breast (Pectoralis Major) were assessed at 0 and 5 days postmortem. A total of 216 female pheasant chicks were enrolled into the study. Twenty-four birds were euthanased at the start of the study, and samples of blood, breast muscle, leg muscle (M. Peroneus Longus and M. Gastrocnemius), heart, liver, kidney and gizzard were collected for determination of total Se. Remaining birds were blocked by live weight and randomly allocated to one of four dietary treatments (n = 48 birds/treatment) that either differed in Se source (SY v. SS) or dose (control (0.17 mg total Se/kg), SY-L and SS-L (0.3 mg/kg total Se as SY and SS, respectively) and SY-H (0.45 mg total Se/kg)). Following 42 and 91 days of treatment, 24 birds per treatment were euthanased, and samples of blood, breast muscle, leg muscle, heart, liver, kidney and gizzard were retained for determination of total Se and the proportion of total Se comprised as SeMet or SeCys. Whole blood GSH-Px activity was determined at each time point. Tissue GSH-Px activity and TBARS were determined in breast tissue at the end of the study. There were increases in both blood and tissues to the graded addition of SY to the diet (P < 0.001), but the same responses were not apparent with the blood and tissues of selenite-supplemented birds receiving a comparable dose (SY-L v. SS-L). Although there were differences between tissue types in the distribution of SeMet and SeCys, there were few differences between treatments. There were effects of treatment on erythrocyte GSH-Px activity (P = 0.012) with values being higher in treatments SY-H and SS-L when compared with the negative control and treatment SY-L. There were no effects of treatment on tissue GSH-Px activity, which is reflected in the overall lack of any treatment effects on TBARS.     

A comparative study on effect of dietary selenium and vitamin E on some antioxidant enzyme activities of liver and brain tissues

Since selenium and vitamin E have been increasingly recognized as an essential element in biology and medicine, current research activities in the field of human medicine and nutrition are devoted to the possibilities of using these antioxidants for the prevention or treatment of many diseases. The present study was aimed at investigating and comparing the effects of dietary antioxidants on glutathione reductase and glutathione peroxidase activities as well as free and protein-bound sulfhydryl contents of rat liver and brain tissues. For 12–14 wk, both sex of weanling rats were fed a standardized selenium-deficient and vitamin E-deficient diet, a selenium-excess diet, or a control diet. It is observed that glutathione reductase and glutathione peroxidase activities of both tissues of the rats fed with a selenium-deficient or excess diet were significantly lower than the values of the control group. It is also shown that free and bound sulfhydryl concentrations of these tissues of both experimental groups were significantly lower than the control group. The percentage of glutathione reductase and glutathione peroxidase activities of the deficient group with respect to the control were 50% and 47% in liver and 66% and 61% in the brain, respectively; while these values in excess group were 51% and 69% in liver and 55% and 80% in brain, respectively. Free sulfhydryl contents of the tissues in both experimental groups showed a parallel decrease. Furthermore, the decrease in protein-bound sulfhydryl values of brain tissues were more pronounced than the values found for liver. It seems that not only liver but also the brain is an important target organ to the alteration in antioxidant system through either a deficiency of both selenium and vitamin E or an excess of selenium alone in the diet.     

Effects of excess selenomethionine on selenium status indicators in pregnant long-tailed macaques (Macaca fascicularis)

Forty pregnant long-tailed macaques were treated daily for 30 d with 0, 25, 150 or 300 μg selenium as L-selenomethionine/kg body weight. Erythrocyte and plasma selenium and glutathione peroxidase specific activities, hair and fecal selenium, and urinary selenium excretion were increased by and were linearly related to L-selenomethionine dose. Hair selenium was most sensitive to L-selenomethionine dose, with an 84-fold increase in the 300 μg selenium/(kg-d) group relative to controls (r=0.917). Daily urinary selenium excretion (80-fold,r=0.958), plasma selenium (22-fold,r=0.885), erythrocyte selenium (24-fold,r=0.920), and fecal selenium (18-fold,r=0.911) also responded strongly to L-selenomethionine. Erythrocyte and plasma glutathione peroxidase specific activities increased 154% and 69% over controls, respectively. Toxicity was associated with erythrocyte selenium >2.3 μg/mL, plasma selenium >2.8 μg/mL, and hair selenium >27 μg/g. Plasma, erythrocyte, and hair selenium concentrations may be useful for monitoring and preventing the toxicity of L-selenomethionine administered to humans in cancer chemoprevention trials.     

Effect of selenium and protein deficiency on selenium and glutathione peroxidase in rats

Twenty-four weanling male Wistar rats were divided into four groups fed diets containing adequate or deficient levels of selenium (0.5 ppm [+ Se] or <0.02 ppm [−Se] and protein (15% [+Pro] or 5% [−Pro]), but adequate levels of all other nutrients for 4 wk to determine the effects of Se deficiency and protein deficiency on tissue Se and glutathione peroxidase (GSHPx) activity in rats. Plasma, heart, liver, and kidney Se and GSHPx were significantly lower in Se-deficient groups in relation to Se-sufficient groups. In Se-deficient groups, Se and GSHPx were significantly higher in −Se−Pro rats in heart, liver, and kidney. Data analysis showed that there were significant interaction effects between dietary Se and protein on Se and GSHPx of rats. It is assumed that under the condition of Se deficiency. a low level of protein may decrease Se and GSHPx utilization, increase GSHPx synthesis, and result in Se redistribution. This could account for high levels of Se and GSHPx in the −Se−Pro rats compared to −Se+Pro rats.     

Schisandrin B protects against tert-butylhydroperoxide induced cerebral toxicity by enhancing glutathione antioxidant status in mouse brain

Schisandrin B (Sch B), a dibenzocyclooctadiene derivative isolated from Fructus Schisandrae, has been shown to produce antioxidant effect on rodent liver and heart. A mouse model of tert-butylhydroperoxide (t-BHP) induced cerebral toxicity was adopted for examining the antioxidant potential of Sch B in the brain. Intracerebroventricular injection of t-BHP caused a time-dependent increase in mortality rate in mice. The t-BHP toxicity was associated with an increase in the extent of cerebral lipid peroxidation and an impairment in cerebral glutathione antioxidant status, as evidenced by the abrupt decrease in reduced glutathione (GSH) level and the inhibition of Se-glutathione peroxidase activity at 5 min following t-BHP challenge. Sch B pretreatment (1 or 2 mmol/kg/day × 3) produced a dose-dependent protection against t-BHP induced mortality. The protection was associated with a decrease in the extent of lipid peroxidation and an enhancement in glutathione antioxidant status in brain tissue detectable at 5 min post t-BHP challenge, with the assessed biochemical parameters being returned to normal values at 60 min in Sch B pretreated mice at a dose of 2 mmol/kg. The ensemble of results suggests the antioxidant potential of Sch B pretreatment in protecting against cerebral oxidative stress.     

Generational differences in selenium status of women

In this cross-sectional study of three generations of women, daughters (19–26 yr), mothers (40–58 yr) and maternal grandmothers (67–84 yr) from the same 10 families in central Ohio were studied to determine the effect of life-cycle differences, including estrogen status, on selenium status. Plasma and red blood cell (RBC) selenium and glutathione peroxidase (GPx) activities were determined and typical dietary selenium intakes were calculated from food-frequency questionnaires. Selenium status was lowest in the oldest generation. Plasma selenium of daughters and grandmothers were significantly lower than those of mothers, and plasma GPx and RBC selenium of grandmothers were also lower than those of the mothers. A positive correlation (r=0.42, p<0.04) was found between plasma estrogen and plasma selenium concentrations. Selenium intakes of all groups were adequate and no differences in selenium intakes were found among groups. The results of this study indicate that selenium status fluctuates during the female life cycle and is related to estrogen status.     

Serum antioxidant enzyme activity in Parkinson's disease

Summary The activities of superoxide dismutase (SOD; EC 1.15.1.1) and glutathione peroxidase (GSHP_x; EC 1.11.1.9.), the enzymes that metabolize the superoxide anion and hydrogen peroxide, respectively, were measured in serum from healthy subjects and patients with Parkinson's disease (PD). The activities of SOD and GSHP_x in patients with PD were higher than those in normal healthy individuals. These results suggest that the increased activities of these enzymes could be due to oxidative stress in the initial stages of this disease.     

Reduced MPTP toxicity in noradrenaline transporter knockout mice

The noradrenergic neurons of the locus coeruleus (LC) are damaged in Parkinson's disease (PD). Neurotoxin ablation of the LC noradrenergic neurons has been shown to exacerbate the dopaminergic toxicity of MPTP, suggesting that the noradrenergic system protects dopamine neurons. We utilized mice that exhibit elevated synaptic noradrenaline (NA) by genetically deleting the noradrenaline transporter (NET), a key regulator of the noradrenergic system (NET KO mice). NET KO and wild-type littermates were administered MPTP and striatal dopamine terminal integrity was assessed by HPLC of monoamines, immmunoblotting for dopaminergic markers and tyrosine hydroxylase (TH) immunohistochemistry. MPTP significantly reduced striatal dopamine in wild-type mice, but not in the NET KO mice. To confirm that the protection observed in the NET KO mice was due to the lack of NET, we treated wild-type mice with the specific NET inhibitor, nisoxetine, and then challenged them with MPTP. Nisoxetine conferred protection to the dopaminergic system. These data indicate that NA can modulate MPTP toxicity and suggest that manipulation of the noradrenergic system may have therapeutic value in PD.     

Effect of vitamin E and selenium supplementation of cockerel diets on glutathione peroxidase activity and lipid peroxidation susceptibility in sperm, testes, and liver

The phospholipids of avian spermatozoa are characterized by high proportions of arachidonic (20:4n-6) and docosatetraenoic (22:4n-6) fatty acids and are therefore sensitive to lipid peroxidation. α-Tocopherol and glutathione peroxidase [GSH-Px] are believed to be the primary components of the antioxidant system of the spermatozoa. The present study evaluates the effect of vitamin E and vitamin E plus Se supplementation of the cockerel diet on GSH-Px activity, vitamin E accumulation, and lipid peroxidation in the spermatozoa, testes, and liver. At the beginning of the experiment 75 Rhode Island Red cockerels were divided into five groups, kept in individual cages, and fed a wheat-barley-based ration balanced in all nutrients. Supplements fed to the different groups were as follows: vitamin E, 0, 20, 200, 20, and 200 mg/kg to groups 1–5, respectively, with groups 4 and 5 also receiving 0. 3 mg Se/kg. The vitamin E supplementation produced increased levels of α-tocopherol in semen, testes, and liver. The inclusion of the Se into the cock diet had a significant (P < 0.01) stimulating effect on GSH-Px activity in seminal plasma, spermatozoa, testes, and liver. The increased vitamin E concentration in the spermatozoa was associated with a reduction in their susceptibility to lipid peroxidation. Similarly, the increased GSH-Px activity provided enhanced protection against lipid peroxidation.     

Effect of supplementation with selenium on whole blood glutathione peroxidase activities and on plasma and tissue selenium concentrations in lambs

In recent years the selenium (Se) intake of the human population of the UK has shown a marked decline from 60 μg/d in 1978 to around 30 μg/d in 1990 owing largely to a significant reduction in the importation of North American wheat for bread-making fluor. Other countries (Finland, for example) in similar situations have instituted fertilization programs in order to raise cereal Se concentrations and thus boost dietary intakes. An alternative approach would be to increase the Se concentration of carcass meat by supplementation of meat animals for a limited period prior to slaughter. A trial was set up with store lambs to evaluate this approach. Sixteen Scottish Blackface lambs were stratified according to live weight and then randomly allocated to one of four treatments: unsupplemented, or 3.5, 7, or 10.5 mg. Se/head/wk. After 14 wk, the lambs were sacrificed and samples of shoulder and thigh muscle, liver, and kidney were obtained for analysis. All three treatments effected an increase in whole blood glutathione peroxidase (GSH-Px) and plasma Se concentrations over controls. Shoulder, thigh, and liver Se exhibited a dose-response relationship to treatment, but kidney Se concentrations were unaffected by treatment. Muscle and some organ meat Se concentrations can therefore be increased by supplementation and could contribute to increased human dietary intakes of the element.     

Effects of selenium status and supplementary seleno-chemical sources on mouse T-cell mitogenesis

Although selenium is thought to be essential for various immune responses, the excess supplementation may have an adverse effect on certain immunological functions. The present study was designed to determine the effective chemical forms of selenium and their optimal levels on T-cell mitogenesis with splenic cells from mice given a selenium-deficient diet for 8 weeks to avoid effects of cellular selenium sources. Although selenium in tissues, except for spleen and thymus, was almost depleted by feeding selenium-deficient diet, the lymphoid organs still contained low levels of selenium. Both activities of cellular glutathione peroxidase (cGPx) and thioredoxin reductase (TR) in liver and splenic cells showed a tendency to decrease by selenium deficiency. However, splenic cells were tolerant against decrease of the selenoenzyme activities, and TR was also more tolerant than cGPx. T-cell proliferation of the selenium-insufficient splenic cells induced by concanavalin A was increased by addition of Na₂SeO₃, Na₂SeO₄, Na₂Se, seleno-dl-cystine, seleno-l-methionine and selenocystamine. Their promoting action was observed at levels lower than 0.1 μmol/L and was completely suppressed at the highest concentration (1 μmol/L), except for selenocystamine. Na₂SeO₃ was one of the efficient selenocompounds for the mitogenesis, which was concomitant with the significant induction of cGPx and TR. However, recovery of cGPx activity in the selenium-insufficient cells by supplementary Na₂SeO₃ was only partial, while TR activity was readily recovered from selenium deficiency. These results therefore indicate that only low levels of selenium is essential for T-cell mitogenesis even in selenium-insufficient splenic cells, and TR, which is readily recovered by Na₂SeO₃, may be the critical enzyme.     

The changes in the antioxidant status of heart during experimental hypomagnesemia in balb/c mice

The present experiment was performed to assess if hypomagnesemia can influence antioxidant status in mice heart. The results could explain possibly a free radical theory of heart damage in magnesium deficiency. We used a rodent model of hypomagnesemia. The magnesium sufficient group received a standard diet whereas a magnesium deficient group received the diet containing a trace amount of magnesium. The activities of the most important antioxidant enzymes – catalase, glutathione peroxidase and superoxide dismutase were assessed in mice heart and liver in a time dependent manner, on the 10th and the 20th day of experiment. The level of magnesium in plasma of animals receiving the magnesium deficient diet dropped twice after the 8th day and four times after the 13th day and then reached a plateau value. The activity of catalase in heart in the magnesium deficient group increased gradually and was significantly (P<0.05) elevated by 27% on the 20th day of experiment whereas the superoxide dismutase activity was significantly decreased by 17% on the 20th day. Glutathione peroxidase activity was insignificantly elevated. The alterations of antioxidant enzyme activities in the heart indicate cardiomyocytes's exposure to oxidative stress, which can be responsible for the cardiac lesions observed during hypomagnesemia.     

Effect of physical restraint on oxidative stress in mice fed a selenium and vitamin E deficient diet

Physical restraint has been associated with increased oxidative damage to lipid, protein, and DNA. The purpose of this experiment was to determine whether physical restraint would further exacerbate oxidative stress in mice fed a selenium (Se) and vitamin E (VE) deficient diet. Three-week-old mice were fed a Torula yeast diet containing adequate or deficient Se and VE. Menhaden oil was added to the deficient diet to impose an additional oxidative stress. After 4 wk feeding, half the mice in each group were restrained for 5 d in well-ventilated conical tubes for 8 h daily. Mice fed the Se and VE deficient diets had increased liver thiobarbituric acid-reactive substance (TBARS) levels and decreased liver glutathione peroxidase (GPX1) activity and α-tocopherol levels. Plasma corticosterone levels were elevated in restrained mice fed the deficient diet compared to unrestrained mice fed the adequate diet. Restraint had no effect on liver TBARS or α-tocopherol levels. Liver GPX1 activity, however, was lower in restrained mice fed the adequate diet. In addition, liver superoxide dismutase (SOD) activity was lower in the restrained mice fed the adequate or deficient diet. Thus, under our conditions, Se and VE deficient diet, but not restraint, increased lipid peroxidation in mice. Restraint, however, decreased antioxidant protection in mice due to decreased activities of GPX1 and SOD enzymes.     

Selenium modifies glutathione peroxidase activity and glutathione concentration in mice exposed to ozone-provoked oxidative stress

The aim of this study was to show the direct effect of selenium on glutathione peroxidase (GSH-Px) activity and GSH/GSSG concentrations in 3- and 6-month-old mice. An ozone-oxygen mixture was used to provoke an oxygen stress. To measure the Se-effect mice were gavaged with sodium selenite. GSH-Px activity and total glutathione concentrations were determined in serum and in the postnuclear fraction of liver and lungs. Additionally glutathione concentrations were determined in whole blood. Both ozone and selenium, administered separately, reduced GSH-Px activity in lungs of 6-month-old animals, while in young mice an opposite effect of Se was observed. Ozone administered jointly with Se did not influence GSH-Px activity in 6-month-old mice, while in young, 3-month-old mice, a stimulatory effect in lungs was observed. There were no significant changes in GSH-Px activity in the liver of 6-month-old mice, but the stimulatory effect occurred in young mice treated with Se and Se & ozone jointly. In young mice, ozone (also ozone with Se) augmented glutathione concentrations. The response to ozone and selenium strictly depended on age and the antagonism between selenium and ozone was observed only in a few cases.     

Early evolution of selenium status and oxidative stress parameters in rat models of thermal injury

The objective of the present study was to measure the relationship between selenium status and oxidative stress in two rat models of thermal injury. A non-lethal third-degree burn injury involving 20% (experiment 1) or 40% (experiment 2) of total body surface area (TBSA) was applied to male Wistar rats. Selenium level, glutathione peroxidase (GPx) activity in plasma, red blood cells (RBC) and tissues (liver, kidney, muscle, and brain), and plasma selenoalbumin (Se-alb) were measured in control rats and in burned rats respectively 6 hours after injury and daily from day 1 to day 5. In parallel, lipid and protein oxidative damages, monitored by plasma and tissue thiobarbituric acid reactive species (TBARs) levels and plasma total thiol groups were assessed.

We observed a decrease of plasma Se and Se-albumin 6 hours after burn injury. In parallel, plasma GPx activity rapidly decreased and remained significantly lower than in control rats. These alterations were enhanced by the burn injury severity. Plasma TBARs followed the same pattern as that of plasma cholesterol, with an initial decrease and an increase at day 3 in 40% TBSA burned rats. Plasma thiol groups decreased in the two experiments indicating plasma protein oxidation.

These results confirm an early oxidative stress in burn injury, and suggest an early selenium mobilization, which might counteract this oxidative stress. These data underline the crucial need of a restored selenium status in burned patients immediately after the burn injury.     

Probucol treatment reverses antioxidant and functional deficit in diabetic cardiomyopathy

Earlier we reported that probucol treatment subsequent to the induction of diabetes can prevent diabetes-associated changes in myocardial antioxidants as well as function at 8 weeks. In this study, we examined the efficacy of probucol in the reversal of diabetes induced myocardial changes. Rats were made diabetic with a single injection of streptozotocin (65 mg/kg, i.v.). After 4 weeks of induction of diabetes, a group of animals was treated on alternate days with probucol (10 mg/kg i.p.), a known lipid lowering agent with antioxidant properties. At 8 weeks, there was a significant drop in the left ventricle (LVSP) and aortic systolic pressures (ASP) in the diabetic group. Hearts from these animals showed an increase in the thiobarbituric acid reacting substances (TBARS), indicating increased lipid peroxidation. This was accompanied by a decrease in the myocardial antioxidant enzymes activities, superoxide dismutase (SOD) and glutathione peroxidase (GSHPx). Myocardial catalase activity in the diabetic group was higher. In the diabetic + probucol group both LVSP and ASP showed significant recovery. This was also accompanied by an improvement in SOD and GSHPx activities and there was further increase in the catalase activity. Levels of the TBARS were decreased in this group. These data provide evidence that diabetic cardiomyopathy is associated with an antioxidant deficit which can be reversed with probucol treatment. Improved cardiac function with probucol may be due to the recovery of antioxidants in the heart.