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Methionine restriction (MR) dramatically extends the healthspan of several organisms. Methionine-restricted rodents have less age-related pathology and increased longevity as compared with controls, and recent studies suggest that humans might benefit similarly. Mechanistically, it is likely that the decreased IGF-1 signaling that results from MR underlies the benefits of this regimen. Thus, we hypothesized that interventions that decrease IGF-1 signaling would also produce MR-like healthspan benefits. Selenium supplementation inhibits IGF-1 signaling in rats and has been studied for its putative healthspan benefits. Indeed, we show that feeding mice a diet supplemented with sodium selenite results in an MR-like phenotype, marked by protection against diet-induced obesity, as well as altered plasma levels of IGF-1, FGF-21, adiponectin, and leptin. Selenomethionine supplementation results in a similar, albeit less robust response, and also extends budding yeast lifespan. Our results indicate that selenium supplementation is sufficient to produce MR-like healthspan benefits for yeast and mammals., Competing Interests: JP, SP, JJ No competing interests declared, JT Senior editor, eLife, (© 2021, Plummer et al.)

Mastitis is the most costly disease of dairy cows. A pro-active approach includes insuring adequate levels of selective trace minerals. The aim of this study was to determine the effect of two different commercially available, injectable selenium products, (sodium) Na-selenite (inorganic) and (selenium) Se-methionine (organic), on milk composition and on serum and milk selenium concentrations in high-yielding Holstein cows on total mix ration. Sixty multiparous cows were randomly selected into three groups of 20, one control group and two groups supplemented with injectable trace minerals. Blood and milk samples were collected over a period of 60 days. No specific change was indicated in milk yield, lactose, milk urea nitrogen (MUN) and milk pH levels compared with baseline values. The Se-methionine supplemented group showed a numerical increase in total milk protein percentage. In the group injected with Se-methionine, a negative correlation was present for the initial 72 hours between serum selenium concentration and somatic cell count (SCC) and a highly significant (p 0.001) increase in milk selenium concentration for the initial 24 hours. Serum selenium concentration of Se-methionine-supplemented cows was however not significantly changed. Injection of Na-selenite led to a 60-day initial increase in serum selenium concentration above baseline levels and a significant milk selenium concentration on day 1 but to a negative correlation between serum selenium concentration and SCC. Differences in serum and milk selenium concentrations followed with the use of organic and inorganic selenium injectables. Injectable Na-selenite, as selenium, can be of important value for cattle farmers if supplemented on strategically physiological periods to improve production, reproduction and immunity.

In this study, the effects of three doses (diets containing <0.01, 0.15, 0.40 mg kg -1 Se) and two forms (sodium selenite and selenomethionine) of dietary Se supplementation on the intestinal physiology of untreated, dextran sodium sulfate-treated, and Salmonella typhimurium-infected mice were evaluated. The underlying modes of action of the varied doses and forms of Se supplementation were analyzed using fecal metabolomic and jejunal proteomic approaches. Compared with adequate Se (0.15 mg kg -1 Se) supplementation, Se-deficiency supplementation adversely affected the gut barrier and intestinal immune responses of the untreated mice and increased their susceptibility to experimental colitis and pathogen infection. In contrast, supranutritional Se (0.40 mg kg -1 Se) supplementation improved mouse intestinal physiology compared with adequate Se supplementation. Varied doses of Se supplementation differentially perturbed the fecal metabolic profiles of and jejunal protein expression in mice. Further, both forms of dietary Se supplementation, i.e., sodium selenite and selenomethionine, showed similar effects on the gut barrier and intestinal immune homeostasis but differentially affected fecal metabolites, such as neurosubstances and immunomodulators, and induced significant proteomic variations in various pathways, including the xenobiotic detoxification pathway and glutathione metabolism. Our results indicate that the doses and chemical forms of Se should be considered when developing dietary nutritional supplements for gut health.

A total of 200 healthy 28-day-old male Jiangnan White geese were used to investigate the free radical scavenging ability, reduced glutathione (GSH) and thioredoxin systems, and the concentrations of reactive oxygen metabolites (ROM), malondialdehyde (MDA), and protein carbonyl (PC) in geese fed diets with organic selenium (Se) (Selenomethionine, SeMet) and inorganic Se (sodium selenite, SS). All geese were randomly allotted into 4 groups with 5 replicates of 10 geese each, and received basal diet supplemented with 0.3 mg Se/kg SS, 0.2, 0.3 and 0.4 mg Se/kg SeMet until 70 D of age, respectively. Geese in the SS and SeMet groups exhibited similar growth performance. Diet with SeMet increased the scavenging abilities of 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt free radical (ABTS•+, P < 0.001) and superoxide radical (O2-•, P = 0.002) in the serum of geese, as well as the scavenging abilities of ABTS•+ (P = 0.023), hydroxyl radical (P = 0.009) and O2-• (P = 0.019) in the liver of geese. Compared to the SS group, SeMet increased hepatic GSH concentration (P = 0.002), the activities of glutathione peroxidase (P = 0.031), γ-glutamate cysteine ligase (P < 0.001), and thioredoxin reductase (P < 0.001), and decreased the concentrations of ROM, MDA, and PC in the serum and liver of geese (P < 0.05). In conclusion, dietary SeMet inclusion would be more effective than SS in increasing the antioxidant capacity of geese, possibly by improving GSH and thioredoxin systems, and 0.2 mg Se/kg SeMet in goose diet is recommended., (© 2019 Poultry Science Association Inc.)

A field study in periparturient sows fed different dietary concentrations of either sodium selenite or L-selenomethionine (SeMet) was conducted to evaluate feed intake, haematological and biochemical parameters as well as to describe some key selenium (Se) species, namely selenoprotein P (SelP), selenoalbumin (SeAlb) and selenomethionine (SeMet) as well as total Se in plasma, colostrum and milk. Thirty-two sows were allotted to four treatments from 30 days (d) prepartum throughout on average a 32 d lactation period. Sodium selenite supplemented diets contained 0.40 and 0.60 mg Se/kg feed, while SeMet supplemented feed contained 0.26 and 0.43 mg Se/kg feed. Concentrations of sodium selenite and SeMet in complete feed exceeded the upper limits for total dietary Se and added organic Se, respectively, according to the European Union legislation. Blood samples were collected at initiation of the study, at farrowing and at weaning. Colostrum samples were collected at farrowing and milk samples at weaning. Se species were subjected to liquid chromatography, and total Se and Se species were determined using inductively coupled plasma mass spectrometry. The SeMet supplemented diets resulted in higher feed intake and in higher levels of total Se, SelP, SeAlb and SeMet in colostrum compared with sows fed sodium selenite. Similar results were obtained for levels of total Se and SeMet in milk at weaning. The higher dietary sodium selenite concentration in sows' feed did not increase the Se transfer into colostrum or milk when compared with those receiving the lower level of sodium selenite. However, the increase in serum-Zn from initiation until farrowing, observed in sows fed SeMet as well as the higher glutamate dehydrogenase activity in sodium selenite supplemented sows in this period might indicate a higher requirement of antioxidant defence in sodium selenite-supplemented sows. To our knowledge, the present data on Se species in plasma, colostrum and milk of sows represent the most complete investigation of Se in sows conducted to date. A higher amount of the above-mentioned Se species in the colostrum of sows supplemented with SeMet might strengthen the piglets' antioxidative system and passive immunity as well as improve their average daily weight gain. The higher feed intake in sows fed diets supplemented with SeMet is an interesting finding that warrants further investigation., (Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Selenium (Se) poisoning by different forms of Se occurs in the United States. However, the toxicokinetics of different selenocompounds after oral ingestion is not well documented. In this study the toxicokinetics of Se absorption, distribution and elimination were determined in serum and whole blood of lambs that were orally dosed with increasing doses of Se as sodium selenite (inorganic Se) or selenomethionine (SeMet, organic Se). Thirty-two lambs were randomly assigned to eight treatment groups, with four animals per group. Se was administered at 1, 2 or 3 mg kg -1 body weight, as either sodium selenite or SeMet with proper control groups. Blood and serum were collected at predetermined time points for 7 days post-dosing. Resulting Se concentrations in both serum and whole blood from SeMet treatment groups were significantly greater than those given equimolar doses of Se as sodium selenite. Se concentrations in serum and whole blood of lambs dosed with SeMet peaked at significantly greater concentrations when compared with lambs dosed with equimolar doses of sodium selenite. Based on the serum and whole blood kinetics, the rate of Se absorption was greater for SeMet than for sodium selenite although rates of absorption for both Se forms decreased with increasing dose. The rates of Se elimination increased with dose. These results demonstrate that SeMet has a greater absorption rate and a similar retention time resulting in a greater area under the curve and thus bioavailability than sodium selenite, which must be considered in both overdose and nutritional exposures. Published 2016. This article is a U.S. Government work and is in the public domain in the USA., (Published 2016. This article is a U.S. Government work and is in the public domain in the USA.)

It is thought that zinc and selenium deficiency may play a significant role in the etiology of prostate cancer. Although joint zinc and selenium supplementation is frequently applied in the prevention of prostate diseases, the bioavailability of these elements in the prostate after co-administration is still unknown. The study examines the effect of subchronic supplementation of zinc gluconate and selenium compounds (sodium selenite or selenomethionine), administered together or separately, on their bioavailability in the prostate, as well as the induction of metallothionein-like proteins (MTs) bound to zinc in the prostate and liver. Zinc concentration in the dorso-lateral lobe of the prostate was significantly elevated already after the first month of supplementation of zinc alone. In the supplementation period, the MTs level increased together with zinc concentration. In contrast, the ventral lobe of the prostate did not demonstrate significantly higher levels of zinc until after three months of supplementation, despite the MTs induction noted after one-month supplementation. Increased selenium levels in the dorsolateral lobe were observed throughout the administration and post-administration periods, regardless of the selenium compound used or whether zinc was co-administered. The results of our studies suggested for the first time that these elements should not be administered jointly in supplementation., Competing Interests: The authors declare no conflict of interest.

This trial was conducted in a 2 × 3 + 1 factorial arrangement based on a completely randomized design to evaluate the effects of different dl-selenomethionine (dl-Se-Met) and sodium selenite (SS) levels on growth performance, immune functions and serum thyroid hormones concentrations in broilers. A total of 840 Ross 308 broilers (7 days old) were allocated by body weight to seven treatments (three replicates of 40 birds each treatment) including (1) basal diet (containing 0.04 mg of selenium (Se)/kg; control) without supplementary Se; (2, 3 and 4) basal diet + 0.05, 0.15 or 0.25 mg/kg Se as SS; (5, 6 and 7) basal diet + 0.05, 0.15 or 0.25 mg/kg Se as dl-Se-Met. The experiment lasted 42 days. The results revealed that dietary Se supplementation improved (p < 0.05) average daily gain, feed efficiency, immune organ index, serum immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM) and triiodothyronine (T3 ) concentrations and decreased (p < 0.01) thyroxine (T4 )/T3 ratio in serum compared with the control. Broilers receiving the dl-Se-Met-supplemented diets had higher (p < 0.05) feed efficiency, thymus index, the amounts of IgA, IgG, IgM and T3 as well as lower (p < 0.05) serum T4 concentrations and T4 /T3 ratio than those consuming the SS-supplemented diets. Serum IgA and IgM levels of broilers fed 0.15 mg Se/kg were significantly higher (p < 0.05) than those of broilers fed 0.05 or 0.25 mg Se/kg. In summary, we concluded that dl-Se-Met is more effective than SS in increasing immunity and promoting conversion of T4 to T3 , thus providing an effective way to improve the growth performance of broilers. Besides, based on a consideration of all experiment indices, 0.15 mg Se/kg was suggested to be the optimal level of Se supplementation under the conditions of this study., (Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.)

The aim of this study was to compare the effect of DL-selenomethionine (SM) with 2 routinely used Se sources, sodium selenite (SS) and seleno-yeast (SY), on relative bioavailability based on antioxidant activity and tissue Se content. Six hundred thirty 131-day-old brown laying hens were randomly assigned to 7 treatments for 168 d (24 wks) with 6 replicates of 15 hens per replicate. The SS and SY animals were supplemented a cornmeal and soybean diet that supplied a total Se 0.3 mg/kg whereas SM was added at 4 different levels to the total Se at 0.1, 0.3, 0.5 and 0.7 mg/kg. All hens fed the Se-supplemented diet showed higher glutathione peroxidase (GSH-Px) activity (P < 0.01), higher superoxide dismutase (SOD) activity (P < 0.05), lower malondialdehyde (MDA) content (P < 0.05) in plasma, and greater Se contents in egg yolks, albumen, leg muscle, breast muscle, liver, and plasma compared with those fed the control diet (P < 0.01). The organic sources (SY and SM) exhibited a greater ability to increase the GSH-Px activity (P < 0.01) and Se content in albumen (P < 0.01), leg, and breast muscles (P = 0.0099 and P = 0.0014, respectively) than the SS that was added at 0.3 mg Se/kg. The higher SM added levels increased the GSH-Px activity until the dose of 0.5mg Se/kg (P < 0.01).The greater Se concentrations in albumen, muscle and liver appeared in the higher SM-added level, as well as above the dose of 0.1 mg Se/kg (P < 0.01). In addition, hens fed the diet with SM accumulated more Se in albumen, leg, and breast muscle than those fed diets with SY (P < 0.05). These results confirmed the higher ability of organic Se sources to increase the antioxidant activity and Se deposition in egg albumen, leg, and breast muscles compared with SS, and demonstrated a significantly better efficiency of SM compared with SY for albumen and muscle Se enrichment., (© 2015 Poultry Science Association Inc.)

This study evaluated the effect of different dietary vitamin E levels and different selenium sources on the productive and reproductive performance of broiler breeders. In total 640 females and 64 males between 22 and 52 weeks old were studied. A completely randomized experimental design in factorial arrangement, with 4 treatments of 8 replicates with 20 females and 2 males each, was applied. Treatments consisted of 2 vitamin E levels (30 and 120 mg/kg) and two selenium sources (sodium selenite and zinc-L-selenomethionine). Egg production (rate of lay and eggs per breeder), egg characteristics (egg, yolk, eggshell, and albumen weights), fertility, incubation responses (egg weight loss during incubation, hatchability, and hatching window), and hatchling characteristics (weight and yield) were evaluated. There was no influence of dietary vitamin E levels or selenium sources on egg production (P > 0.05). Mature breeders (47 weeks old) fed zinc-L-selenomethionine and 120 mg vitamin E/kg feed produced heavier eggs and albumen. Hatchability of the eggs of breeders fed 120 mg vitamin E/kg feed was higher than breeders fed 30 mg vitamin at 29 wks. The dietary inclusion of organic selenium also promoted heavier hatchling weight until egg production peak (33 wk), but did not influence hatchling quality or hatching window. It was concluded that the dietary supplementation of zinc-L-selenomethione and vitamin E (120 mg/kg feed) could be used to improve egg characteristics and incubation response., (© 2015 Poultry Science Association Inc.)

The European population is only suboptimally supplied with the essential trace element selenium. Such a selenium status is supposed to worsen colitis while colitis-suppressive effects were observed with adequate or supplemented amounts of both organic selenomethionine (SeMet) and inorganic sodium selenite. In order to better understand the effect of these selenocompounds on colitis development we examined colonic phenotypes of mice fed supplemented diets before the onset of colitis or during the acute phase. Colitis was induced by treating mice with 1% dextran sulfate sodium (DSS) for seven days. The selenium-enriched diets were either provided directly after weaning (long-term) or were given to mice with a suboptimal selenium status after DSS withdrawal (short-term). While long-term selenium supplementation had no effect on colitis development, short-term selenite supplementation, however, resulted in a more severe colitis. Colonic selenoprotein expression was maximized in all selenium-supplemented groups independent of the selenocompound or intervention time. This indicates that the short-term selenite effect appears to be independent from colonic selenoprotein expression. In conclusion, a selenite supplementation during acute colitis has no health benefits but may even aggravate the course of disease.

Developing new sources of organic Se has potential benefit for animal production and human nutrition via animal-based foods enriched in Se. The objectives of this trial were to compare L-selenomethionine with another organic Se source, Se-enriched yeast (SelPlex 2300), and sodium selenite, an inorganic Se source, against a commercial control diet. The effect of source and the dosage of Se supplementation on Se in eggs and blood variables was investigated. Ten treatments were used with 18 laying hens per group. In addition to the control diet, the control diet was supplemented with L-selenomethionine, Se-enriched yeast, or sodium selenite at 0.1, 0.3, or 0.5 mg/kg of Se. The feeding trial lasted 8 wk. Birds in the different treatment groups all showed good performance. At d 0 and 56, Se and glutathione peroxidase (GPx) were analyzed in 10 blood samples per group. After supplementing the diets for 56 d, significantly higher Se levels in serum and egg contents were reached for the Se-supplemented groups compared with the control. Supplementing 0.3 and 0.5 mg/kg of L-selenomethionine or Se-enriched yeast instead of 0.1 mg/kg significantly increased the serum Se levels, whereas no significant increase was found for sodium selenite. No effect of Se source or dosage was observed on serum GPx levels. Selenium in eggs was significantly affected by dosage and source of Se. The Se supplementation level in the feed was reflected in the eggs, with the highest and lowest values for 0.5 and 0.1 mg/kg, respectively, and values in between for the 0.3 mg/kg supplementation level. A dose response was most pronounced for L-selenomethionine, followed by Se-enriched yeast, and was least when Se was added as sodium selenite. It can be concluded that Se from organic sources was more bioavailable than the inorganic Se source as evidenced by blood and egg Se levels. Within the organic Se sources, L-selenomethionine showed higher Se transfer to eggs than Se-enriched yeast., (©2014 Poultry Science Association Inc.)

An 8-wk experiment using 180 Lingnan Yellow broiler breeders was conducted to investigate the effect of different sources of Se on the concentration and gene expression of selenoprotein P (SEPP1) in broiler breeders and their offspring. After receiving a low-Se basal diet for 8 wk, broiler breeders were randomly allocated to 3 treatments (6 replicates per treatment) and fed corn-soy-based diets supplemented with 0.15 mg/kg of Se from sodium selenite (SS), Se-enriched yeast (SY), and selenomethionine (SM), respectively. Fertile eggs from different replicates were collected during the last week of the experiment and then incubated in different incubator trays in the same incubator. The concentrations and mRNA levels of SEPP1 were determined in liver and kidney of broiler breeders and their offspring, as well as the serum SEPP1 concentration. Compared with SS, both SY and SM significantly increased (P < 0.05) the concentration and mRNA level of SEPP1 in 1-d-old chicks. In broiler breeders, the serum and liver SEPP1 concentrations were notably increased by the use of organic Se (P < 0.05), whereas no differences were found in the kidney. Moreover, the SEPP1 mRNA level in the liver was remarkably elevated (P < 0.05) in organic Se treatments, but also no differences were observed in the kidney. Results of this study indicate that the use of organic Se (SY or SM) in maternal diets is very effective for increasing the concentration and mRNA level of SEPP1, especially in their offspring. No differences between SY and SM were observed.

Background: Hashimoto's thyroiditis is a common auto-immune disorder. The most common presenting symptoms may include anxiety, negative mood, depression, dry skin, cold intolerance, puffy eyes, muscle cramps and fatigue, deep voice, constipation, slow thinking and poor memory. Clinical manifestations of the disease are defined primarily by low levels of thyroid hormones; therefore it is treated by hormone replacement therapy, which usually consists of levothyroxine (LT4). Selenium might reduce antibody levels and result in a decreased dosage of LT4 and may provide other beneficial effects (e.g. on mood and health-related quality of life)., Objectives: To assess the effects of selenium supplementation on Hashimoto's thyroiditis., Search Methods: We searched the following databases up to 2 October 2012: CENTRAL in The Cochrane Library (2012, Issue 10), MEDLINE, EMBASE, and Web of Science; we also screened reference lists of included studies and searched several online trial registries for ongoing trials (5 November 2012)., Selection Criteria: Randomised controlled clinical trials that assessed the effects of selenium supplementation for adults diagnosed with Hashimoto's thyroiditis., Data Collection and Analysis: Study selection, data extraction, assessment of risk of bias, and analyses were carried out by two independent review authors. We assessed the quality of the evidence of included studies using GRADE. We were unable to conduct a meta-analysis because clinical heterogeneity between interventions that were investigated is substantial., Main Results: Four studies at unclear to high risk of bias comprising 463 participants were included. The mean study duration was 7.5 months (range 3 to 18 months). One of our primary outcomes－'change from baseline in health related quality of life'－and two of our secondary outcomes－'change from baseline in LT4 replacement dosage at end of the study' and 'economic costs'－were not assessed in any of the studies. One study at high risk of bias showed statistically significant improvement in subjective well-being with sodium selenite 200 μg plus titrated LT4 compared with placebo plus titrated LT4 (relative risk (RR) 4.67, 95% confidence interval (CI) 1.61 to 13.50; P = 0.004; 36 participants; number needed to treat (NNT) = 2 (95% CI 2 to 3)).Selenomethionine 200 μg reduced the serum levels of anti-thyroid peroxidase antibodies compared with placebo in two studies (mean difference (MD) -917 U/mL, 95% CI -1056 to -778; P < 0.001; 85 participants) and (MD -345 IU/mL, 95% CI -359 to -331; P < 0.001; 169 participants). Pooling of the studies was not feasible due to marked clinical heterogeneity (I(2) = 99%). In a further comparison within the first study where selenomethionine was combined with LT4 the reduction in TPO antibodies was even more noticeable (MD -1508 U/mL, 95% CI -1671 to -1345; P < 0.001; 86 participants). In a third study, where LT4 was added to both intervention arms, a reduction in serum levels of anti-thyroid peroxidase antibodies favoured the selenomethionine arm as well (MD -235 IU/mL, 95% CI -374 to -95; P = 0.001; 88 participants). Although the changes from baseline were statistically significant in these three studies, their clinical relevance is unclear. Serum antibodies were not statistically significantly affected in the study comparing sodium selenite 200 μg plus titrated LT4 with placebo plus titrated LT4 (MD -25, 95% CI -181 to 131; P = 0.75; 36 participants).Adverse events were reported in two studies (1 of 85 and 1 of 88 participants, respectively). Selenium supplementation did not appear to have a statistically significant impact on the incidence of adverse events (RR 2.93, 95% CI 0.12 to 70.00; and RR 2.63, 95% CI 0.11 to 62.95)., Authors' Conclusions: Results of these four studies show that evidence to support or refute the efficacy of selenium supplementation in people with Hashimoto's thyroiditis is incomplete. The current level of evidence for the efficacy of selenium supplementation in the management of people with Hashimoto's thyroiditis is based on four randomised controlled trials assessed at unclear to high risk of bias; this does not at present allow confident decision making about the use of selenium supplementation for Hashimoto's thyroiditis. This review highlights the need for randomised placebo-controlled trials to evaluate the effects of selenium in people with Hashimoto's thyroiditis and can ultimately provide reliable evidence to help inform clinical decision making.

Project: Selenium deficiency has been associated with enhanced propensity of seizures in man and laboratory animals. Therefore, the present study has been designed to investigate the anti-convulsant effect of sodium selenite and seleno-dl-methionine on pentylenetetrazole induced seizures in mice and the role of prostaglandin receptor activation in the proposed anticonvulsant effect of sodium selenite., Procedure: Sodium selenite (1, 3 and 10 mg kg(-1), i.p.) and seleno-dl-methionine (0.3, 1 and 3 mg kg(-1), i.p.) was used to evaluate the potential effect on pentylenetetrazole induced seizures in mice. Pentylenetetrazole induced seizures were assessed in terms of onset time of straub's tail phenomenon, jerky movements of the whole body and convulsions. Additionally, an isobolographic study design was used to examine the interaction between sodium selenite and celecoxib (a cyclooxygenase-2 inhibitor). Sodium selenite and seleno-dl-methionine significantly attenuated pentylenetetrazole induced seizures in mice., Results: Prior administration of misoprostol (a selective agonist of prostaglandin E(1) receptors) markedly attenuated the anticonvulsant effect of sodium selenite as well as seleno-dl-methionine in mice. However, the administration of misoprostol per se did not produce any behavioral changes. Further, sodium selenite was observed to exert a synergistic interaction with celecoxib., Conclusions: Selenium induced reduction in seizure like behavior might be ascribed to the activation of a prostaglandin E(1) receptor activation linked mechanism. It is further proposed that sodium selenite exerts a synergistic anti-convulsant effect with celecoxib indicating the therapeutic usefulness of combining the two agents to treat epilepsy., (Copyright © 2012 Elsevier GmbH. All rights reserved.)

A 2×2 factorial arrangement of treatments in randomized design was conducted to investigate the effect of different selenomethionine (SM) sources and levels on the productive performance of breeder hens and the Se distribution in the inclusion of eggs and serum and tissues of breeder hens and its offspring. A total of 480 Ling-Nan-Huang breeder hens, 48 weeks of age, were allocated to four treatments, each of which included three replicates of 40 hens. Pretreatment period was 2 weeks, and the experiment lasted 8 weeks. Two SM forms of DL-SM and L-SM were supplemented at 0.15 or 0.30 mg Se/kg into the basal diet. Results showed that the Se level of 0.15 mg/kg supplemented in the diet, compared to 0.30 mg/kg, significantly elevated the percentage of egg production (p<0.05), hatchability (p<0.01), and birthrate (p<0.01), whereas the Se level of 0.30 mg/kg led to a higher Se content in egg contents, serum, and all tissues (p<0.01). In addition, the form of DL-SM showed a significant increase in Se content of egg inclusion (p<0.01), serum (p<0.01), and all tissues (p<0.01, except breeder hens' pancreas and its offspring's liver and breast muscle). The birthrate and yolk Se content were markedly influenced by the interaction between Se source and Se level (p<0.01). The above results suggested that DL-SM, compared to L-SM, had a similar equal effect on the performance of breeder hens, but DL-SM was superior to L-SM with respect to selenium distribution in egg inclusion, serum, and tissues.

The studies were carried out on nude mice bearing human colorectal carcinoma SW480 cell line xenografts to evaluate the chemotherapeutic potential of selenium containing compounds such as sodium selenite (SSe) and selenomethionine (SeMet). Three doses of anticancer drugs were used, including 0.1 mg/kg/day SSe (LSSe), 2 mg/kg/day SSe (HSSe), and 2 mg/kg/day SeMet. We explored the anticancer effect of SSe and SeMet administered by IP injection for 21 days. We observed the pathologic changes and the cell apoptosis in tumor tissue by HE staining and TUNNEL assay after HSSe and SeMet treatment. GSH level and antioxidant enzyme GPX activity in tumor tissues were assessed. In addition, Western blotting was used to detect the expression of apoptosis-related proteins. The results suggested that HSSe and SeMet had significantly inhibited tumor growth in vivo. We also observed the pathologic changes and cell apoptosis in tumor tissues after HSSe and SeMet treatment. GSH level was a bit increased but the GPX activity was reduced. Moreover, SSe and SeMet treatment downregulated the expression of the protein Bcl-xL, increased the expression of Bax, Bad, and Bim, and activated caspase-9. SSe and SeMet may be the selective, low-toxic anticancer agents to treat human colorectal carcinoma cancer.

Background: 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., Methods: 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., Results: 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., Conclusions: 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.

The effect of three different doses of dietary L-selenomethionine (SM) and sodium selenite (SS) on skin selenium (Se) content, glutathione peroxidase (GPx) activity, Langerhans cell (LC) and mast cell numbers in ultraviolet radiation-B (UVB)-irradiated and unirradiated C3H/HeN mice was determined. After weaning, groups of mice were given Se-deficient, Se-adequate, or Se-high diets. Six weeks later, some animals in each group were exposed to a single UVB dose (acute), while others were exposed three times weekly for the following 40 weeks (chronic). The skin Se content and GPx activity increased in all the Se-supplemented groups, and the latter was not altered by UVB exposure. Generally, the Se-containing diets caused an increase in LC numbers at 6 weeks and a further rise at 40 weeks, but did not prevent the loss induced by acute or chronic UVB radiation. Skin mast cell numbers were highest in animals fed the Se-deficient diet after 6 and 40 weeks. Acute and chronic UVB radiation decreased the mast cell number and dietary Se did not prevent the reduction. While the present study shows that Se plays an important role in governing the number of LCs and mast cells in the skin, no protective effect against the immunomodulating properties of UVB radiation on these cell types was observed. However, this conclusion may only apply to the experimental conditions chosen, and additional studies at different Se dosages and reduced intensities of chronic UVB exposure are required to confirm the results.

Nutritional selenocompounds are transformed into the assumed common intermediate selenide, which is utilized for the synthesis of selenoenzymes or transformed into methylated metabolites for excretion. Hence, selenocompound metabolites can be traced only with labeled selenium. Here we applied a new tracer method for the metallomics of biometals using simultaneous speciation of each metallome labeled with different homo-elemental isotopes to metabolism and availability of selenium. Rats were depleted of endogenous natural abundance selenium by feeding a single selenium stable isotope ((82)Se-selenite) and then administered (76)Se-selenite and (77)Se-selenomethionine ((77)Se-SeMet)simultaneously. Biological samples were subjected to quantification and speciation analysis by HPLC-ICPMS. Metabolites of the labeled (76)Se and (77)Se and interaction with endogenous selenium were traced and examined without interference from the corresponding endogenous natural abundance isotopes. Differences in the distribution and metabolism among organs and between the two nutritional selenocompounds were compared under exactly identical biological and analytical conditions: (1) selenite was distributed more efficiently than SeMet in organs and body fluids except the pancreas. (2) SeMet was taken up by organs in its intact form. (3) Selenium of SeMet origin was distributed selectively in the pancreas and mostly bound to a protein together with intact SeMet. (4) Selenosugars A and B but not trimethylselenonium (TMSe) were detected in the liver. (5) Selenosugar B and TMSe were detected in the kidneys.

Excess consumption of selenium (Se) accumulator plants can result in selenium intoxication. The objective of the study reported here was to compare the acute toxicosis caused by organic selenium (selenomethionine) found in plants with that caused by the supplemental, inorganic form of selenium (sodium selenite). Lambs were orally administered a single dose of selenium as either sodium selenite or selenomethionine and were monitored for 7 days, after which they were euthanized and necropsied. Twelve randomly assigned treatment groups consisted of animals given 0, 1, 2, 3, or 4 mg of Se/kg of body weight as sodium selenite, or 0, 1, 2, 3, 4, 6, or 8 mg of Se/kg as selenomethionine. Sodium selenite at dosages of 2, 3, and 4 mg/kg, as well as selenomethionine at dosages of 4, 6, and 8 mg/kg resulted in tachypnea and/or respiratory distress following minimal exercise. Severity and time to recovery varied, and were dose dependent. Major histopathologic findings in animals of the high-dose groups included multifocal myocardial necrosis and pulmonary alveolar vasculitis with pulmonary edema and hemorrhage. Analysis of liver, kidney cortex, heart, blood, and serum revealed linear, dose-dependent increases in selenium concentration. However, tissue selenium concentration in selenomethionine-treated lambs were significantly greater than that in lambs treated with equivalent doses of sodium selenite. To estimate the oxidative effects of these selenium compounds in vivo, liver vitamin E concentration also was measured. Sodium selenite, but not selenomethionine administration resulted in decreased liver vitamin E concentration. Results of this study indicate that the chemical form of the ingested Se must be known to adequately interpret tissue, blood, and serum Se concentrations.

Objective: To evaluate the respiratory excretion and elimination kinetics of organic and inorganic selenium after oral administration in sheep., Animals: 38 crossbred sheep., Procedures: Selenium was administered PO to sheep as a single dose of 0, 1, 2, 3, or 4 mg/kg as sodium selenite or selenomethionine. Expired air was collected and analyzed from all sheep at 4, 8, and 16 hours after administration., Results: Clinical signs consistent with selenium intoxication were seen in treatment groups given sodium selenite but not in treatment groups given the equivalent amount of selenium as selenomethionine. However, a distinct garlic-like odor was evident in the breath of all sheep receiving 2 to 4 mg of selenium/kg. The intensity of odor in the breath did not correlate with clinical signs in affected animals receiving sodium selenite treatment., Conclusions and Clinical Relevance: The concentration of selenium in expired air was greater in sheep receiving selenium as selenomethionine than sodium selenite. The concentration of selenium in expired air from sheep receiving high doses of selenium (3 and 4 mg of selenium/kg) was larger and selenium was expired for a longer duration than the concentration of selenium in expired air from sheep receiving low doses of selenium (1 and 2 mg of selenium/kg).

1. Diets containing supplements of selenium (10 mg/kg as sodium selenite), copper (500 mg/kg as copper (II) sulphate) and sodium nitroprusside (SNP 300 mg/kg) as a source of cyanide, were fed singly and in all possible combinations to chicks from 14 to 35 d of age. 2. Both copper and SNP individually alleviated the growth depression caused by excess selenium but interacted adversely with one another. The effect of SNP was to decrease liver selenium but copper increased it. Despite this contrast it is suggested that both achieve their beneficial effects through influences on the fraction of liver selenium that can be reduced to volatile forms by hydrochloric acid and zinc. 3. In a second experiment the effects of diets containing additional selenium (2 mg/kg as sodium selenite or selenomethionine) with or without additional copper (100 mg/kg) or SNP (100 mg/kg) on selenium incorporation into eggs were compared. 4. SNP reduced incorporation from selenite whereas copper had no effect. However, copper reduced the incorporation from selenomethionine into protein fractions of egg white as much as SNP.

The need exists for compounds that will protect individuals from high-dose acute radiation exposure in space and the agents that might be less protective but less toxic and longer acting. Metals and metal derivatives provide a small degree of radioprotection (dose reduction factor < or = 1.2 for animal survival after whole-body irradiation). Emphasis is placed here on the radioprotective potential of selenium (Se). Both the inorganic salt, sodium selenite, and the organic Se compound, selenomethionine, enhance the survival of irradiated mice (60Co, 0.2 Gy/min) when injected IP either before (-24 hr and -1 hr) or shortly after (+15 min) radiation exposure. When administered at equitoxic doses (one-fourth LD10; selenomethionine = 4.0 mg/kg Se, sodium selenite = 0.8 mg/kg Se), both drugs enhanced the 30-day survival of mice irradiated at 9 Gy. Survival after 10-Gy exposure was significantly increased only after selenomethionine treatment. An advantage of selenomethionine is lower lethal and behavioral toxicity (locomotor activity depression) compared to sodium selenite, when they are administered at equivalent doses of Se. Sodium selenite administered in combination with WR-2721, S-2-(3-aminopropylamino)ethylphosphorothioic acid, enhances the radioprotective effect and reduces the lethal toxicity, but not the behavioral toxicity, of WR-2721. Other studies on radioprotection and protection against chemical carcinogens by different forms of Se are reviewed. As additional animal data and results from human chemoprevention trials become available, consideration also can be given to prolonged administration of Se compounds for protection against long-term radiation effects in space.