Search

Selenomethionine (SeMet) is a beneficial organic source of selenium that is extensively used as a food additive owing to its antioxidant and anti-inflammatory properties. Due to the sensitivity of the kidneys to noxious stimuli, they are more susceptible to various injuries. To investigate the protective mechanisms of SeMet supplementation against kidney injury, we established an in vivo experimental model using laying hens treated with SeMet (0.5 mg/kg diet) and/or lipopolysaccharide (LPS) (0.2 mg/kg. BW) and an in vitro model of chicken embryo primary kidney (CEK) cells treated with SeMet (0.075 mM) and with/ without LPS (60 μg/mL). SeMet treatment alleviated the LPS-induced kidney insufficiency and mitochondrial damage. Furthermore, it reduced the expression of TLR4, RIPK3, MLKL, DRP1, NLRP3, and IL-1β in the kidneys of laying hens. RIPK3 is known to induced necroptosis and inflammation by activating of the downstream factors DRP1 and MLKL. To investigate the mechanism whereby SeMet alleviates LPS-induced necroptosis in the kidney, we pretreated CEK cells with TLR4, RIPK3, and DRP1 inhibitors. The results demonstrated that RIPK3 inhibition resulted in a significantly increased in the mitochondrial membrane potential and downregulation of DRP1. Upon the inhibition of DRP1 expression, MLKL, NLRP3, and IL-1β expression also decreased. In summary, SeMet regulates the TLR4/RIPK3/DRP1 signaling pathway to restore the LPS-induced imbalances in mitochondrial dynamics, thereby alleviating necroptosis and inflammation in the kidneys of laying hen. Selenium also increases the expression of selenoproteins. This study provides valuable information for the development of new therapeutic strategies using SeMet to alleviate kidney injury., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial inte rests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This study aimed to compare the effects of various dietary selenium (Se) sources (0.5 mg/kg) on performance, meat quality, and antioxidant capacity in broilers as well as essential trace elements concentrations in their blood and tissues. A total of 360 one-day-old male yellow-feathered chickens (37.00 ± 0.17 g) were randomly allocated to 5 diet treatments: the basal diet (CON) and 4 diets supplemented with sodium selenite (SS), selenomethionine (SM), selenium-enriched yeast (SY), and nano-selenium (NS) for 56 d, respectively, with 6 replicates per treatment and 12 chickens per replicate. Dietary Se supplementation did not affect growth performance and carcass characteristics in broilers (P > 0.05). Supplemental SM enhanced the redness in the pectoral muscle compared to CON and NS (P < 0.05). Supplementation of SY and NS improved the concentrations of Se, copper, manganese, and zinc in the serum (P < 0.05). Supplemental SS also elevated the zinc content in the serum (P < 0.05). Broilers fed the SY diet showed increased Se content in the liver and pectoral muscle compared to those fed CON, SM, and NS diets (P < 0.05). Also, SY improved the pectoral muscle Se concentration compared to SS (P < 0.05). Besides, dietary Se supplementation increased the Se content in the thigh muscle (P < 0.05), with SY showing highest Se deposition. Dietary supplementation with SS, SM, and NS improved the activities of total superoxide dismutase and total antioxidant capacity (T-AOC) in the serum (P < 0.05). Supplemental SY also elevated the T-AOC in the serum (P < 0.05). Additionally, SS and SM enhanced the T-AOC in the liver (P < 0.05). In conclusion, supplemental SM affected meat color. Supplementing diets with various Se sources increased antioxidant capacity and Se content in the thigh muscle of broilers, with SY showing a more pronounced deposition efficiency. Besides, diets supplemented with different Se sources had variable effects on the concentrations of essential trace elements in the serum and tissues of broilers., Competing Interests: DISCLOSURES The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This experiment aims to study the effects of dietary selenium (Se) sources on the production performance, reproductive performance, and maternal effect of breeder laying hens. A total of 2,112 Hyline brown breeder laying hens of 42 wk of age were selected and randomly divided into 3 groups, with 8 repeats in each group and 88 chickens per repeat. The sources of dietary Se were sodium selenite (SS, added at 0.3 mg/kg), L-selenomethionine (L-SM, added at 0.2 mg/kg), and combination of SS and L-SM (SS 0.15 mg/kg + L-SM 0.15 mg/kg). The pretest period was 7 d, and the breeding period was 49 d. Compared with 0.3 mg/kg SS, the addition of 0.2 mg/kg L-SM in the diet significantly increased the hatchability (P < 0.05) and the Se content (P < 0.05) in egg yolk and chicken embryo tissues and improved the activity of yolk glutathione peroxidase (GSH-px) effectively (P < 0.05). Treatment with 0.2 mg/kg L-SM also reduced the content of yolk malondialdehyde (P < 0.05) and significantly improved the antioxidant performance of 1-day-old chicks, as manifested by increased activity of antioxidant enzymes (GSH-px, total antioxidant capacity and the ability to inhibit hydroxyl radicals) in serum, pectoral, heart, and liver (P < 0.05). This treatment decreased the malondialdehyde content (P < 0.05) and increased the expression of liver glutathione peroxidase 4 and deiodinase 1 mRNA (P < 0.05). Adding L-SM to the diets of chickens increased the hatchability of breeder eggs as well as the amount of Se deposited and antioxidant enzyme activity in breeder eggs and embryos. Compared with SS, L-SM was more effectively transferred from the mother to the embryo and offspring, showing efficient maternal nutrition. For breeder diets, the combination of organic and inorganic Se (0.15 mg/kg SS + 0.15 mg/kg L-SM) is an effective nutrient supplementation technology program for effectively improving the breeding performance of breeders and the antioxidant performance and health level of offspring chicks., (Copyright © 2020. Published by Elsevier Inc.)

Background: The association between high selenium (Se) intake and metabolic disorders such as type 2 diabetes has raised great concern, but the underlying mechanism remains unclear., Objective: Through targeted metabolomics analysis, we examined the liver sugar and acylcarnitine metabolism responses to supranutritional selenomethionine (SeMet) supplementation in pigs., Methods: Thirty-six castrated male pigs (Duroc-Landrace-Yorkshire, 62.0 ± 3.3 kg) were fed SeMet adequate (Se-A, 0.25 mg Se/kg) or SeMet supranutritional (Se-S, 2.5 mg Se/kg) diets for 60 d. The Se concentration, biochemical, gene expression, enzyme activity, and energy-targeted metabolite profiles were analyzed., Results: The Se-S group had greater fasting serum concentrations of glucose (1.9-fold), insulin (1.4-fold), and free fatty acids (FFAs,1.3-fold) relative to the Se-A group (P < 0.05). The liver total Se concentration was 4.2-fold that of the Se-A group in the Se-S group (P < 0.05), but expression of most selenoprotein genes and selenoenzyme activity did not differ between the 2 groups. Seven of 27 targeted sugar metabolites and 4 of 21 acylcarnitine metabolites significantly changed in response to high SeMet (P < 0.05). High SeMet supplementation significantly upregulated phosphoenolpyruvate carboxy kinase (PEPCK) activity by 64.4% and decreased hexokinase and succinate dehydrogenase (SDH) activity by 46.5-56.7% (P < 0.05). The relative contents of glucose, dihydroxyacetone phosphate, α-ketoglutarate, fumarate, malate, erythrose-4-phosphate, and sedoheptulose-7-phosphate in the Se-S group were 21.1-360% greater than those in the Se-A group (P < 0.05). The expression of fatty acid synthase (FASN) and the relative contents of carnitine, hexanoyl-carnitine, decanoyl-carnitine, and tetradecanoyl-carnitine in the Se-S group were 35-97% higher than those in the Se-A group (P < 0.05)., Conclusions: Dietary high SeMet-induced hyperglycemia and hyperinsulinemia were associated with suppression of sugar metabolism and elevation of lipid synthesis in pig livers. Our research provides novel insights into high SeMet intake-induced type 2 diabetes., (Copyright © The Author(s) 2020.)

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.)

This study investigated the transfer kinetics of dietary selenite and selenomethionine (SeMet) to the fillet of farmed Atlantic salmon ( Salmo salar ). The uptake and elimination rate constants of the two selenium (Se) forms were determined in Atlantic salmon fed either selenite- or SeMet-supplemented diets followed by a depuration period. The fillet half-life of selenite and SeMet was 779 ± 188 and 339 ± 103 days, respectively. The elimination and uptake rates were used in a simple one-compartmental kinetic model to predict levels in fillet based on long-term (whole production cycle) feeding with given dietary Se levels. Model predictions for Atlantic salmon fed plant-based feeds low in natural Se and supplemented with either 0.2 mg of selenite or SeMet kg -1 gave a predicted fillet level of 0.042 and 0.058 mg Se kg -1 wet weight, respectively. Based on these predictions and the European Food Safety Authority risk assessment of Se feed supplementation for food-producing terrestrial farm animals, the supplementation with 0.2 mg of selenite kg -1 would likely be safe for the most sensitive group of consumers (toddlers). However, supplementing feed to farm animals, including salmon, with 0.2 mg of SeMet kg -1 would give a higher (114%) Se intake than the safe upper intake limit for toddlers.

The aim of the present study was to verify the effect of selenomethionine (SM) supplementation in the diet of chickens on performance, carcass yield, apparent retention, meat quality, and selenium (Se) deposition in tissues. In the first experiment, 2,100 day-old male chicks from the Hubbard Flex strain were randomly distributed in 84 plots with 12 treatments and 7 replicates. The treatments consisted of SM (1,600 ppm) supplementation at levels of 0.3 and 0.5 ppm in substitution of sodium selenite (45.7%) in different preslaughter phases. In the second experiment, 224 day-old male chicks from Hubbard Flex strain were randomly distributed in 28 metabolic cages. Poultry were distributed in 4 treatments with 7 replicates (8 poultry) in the experimental period from 1 to 21 D and experimental plot with 4 poultry aged from 22 to 42 D. Treatments consisted of 4 SM addition levels (0.3, 0.4, 0.5, and 0.6 ppm). In both experiments, the performance (1 to 21 and 1 to 42 D), carcass yield and cuts, apparent retention of Se (33 to 35 D), physical and chemical characteristics of the breast meat were evaluated: objective color, drip loss (DL), cooking loss (CL), pH, peroxide value, and Se deposition in tissues. In experiment I, it was found that SM at 0.3 ppm improved the weight gain and feed conversion of 1 to 42 D. The use of SM at 0.5 ppm resulted in lower DL and CL. The highest Se deposition in muscles was obtained using the SM at 0.5 ppm of 1 to 42 D. Using the SM at 0.5 ppm, only in the last week there was a deposition similar to the use of SM at 0.3 ppm of 1 to 42 D. In experiment II, it can be observed that increased SM levels provided lower DL and lower pH values. Se deposition in tissues of broiler chickens increased linearly at the SM level from 0.3 to 0.6 ppm., (© 2018 Poultry Science Association Inc.)

Fluorosis can induce oxidative stress through leading to reactive oxygen species (ROS) generation. Selenium (Se) can eliminate ROS by direct and indirect manners. In this study, therefore, we investigated the possible protective effects of sodium selenite (SS) and selenomethionine (Se-Met) on fluorine (F)-induced oxidative stress in broilers. A total of 720 1-day-old Lingnan Yellow broilers were allotted to 4 groups (6 replicates of 30 birds each group) and fed with basal diet (control group), 800 mg/kg F (high F group), 800 mg/kg F+0.15 mg Se/kg as SS (SS group), or Se-Met (Se-Met group), respectively. The experiment lasted 50 d. High F group significantly decreased (P < 0.05) the average daily gain (ADG) and feed efficiency (FE) in comparison with control group. The contents of ROS, malondialdehyde, 8-hydroxydeoxyguanosine, protein carbonyl, and cysteinyl aspartate specific proteinases 3 in serum, liver, and kidney were higher (P < 0.05) in high F group than those in control group. Compared with control group, the decreased (P < 0.05) activities of glutathione peroxidase (GSH-Px) and cytoplasmic thioredoxin reductase (TrxR1) as well as contents of selenoprotein P (SelP), total protein (TP), and B-cell lymphoma-2 in serum and tissues were observed in high F group. Moreover, the pathological lesions of liver and kidney in high F group were more than those in control group. However, supplementation with SS and Se-Met could improve ADG and FE, increase SelP and TP concentrations, elevate GSH-Px and TrxR1 activities, minimize the changes of oxidative stress and apoptosis parameters as well as ultrastructure of liver and kidney, whereas the effects of Se-Met were better than those of SS. The results indicated that excess F could result in growth inhibition of broilers through inducing oxidative stress and subsequently caused oxidative damage to biological macromolecules and soft tissues as well as apoptosis, whereas dietary SS and Se-Met supplementation could antagonize high F induced growth retardation by inhibiting oxidative stress and a mechanism of apoptosis regulation and the impact was more with Se-Met.

A study was conducted to evaluate growth performance, carcass and breast yields, and the occurrence and severity of white striping (WS) and wooden breast (WB) myopathies of broilers fed diets supplemented with increasing dietary levels of an organic source of selenium (Zn-L-SeMet). Broilers were fed 6 treatments with 12 replications of 26 birds in a 4-phase feeding program from 1 to 42 days. Corn-soy-based diets were supplemented with 0, 0.2, 0.4, 0.6, 0.8, and 1.0 ppm of Zn-L-SeMet. At 42 d, 6 birds were randomly selected from each pen (n = 72) and processed for carcass and breast yields. Breast fillets were scored for WS and WB at 42 days. Increasing Zn-L-SeMet led to quadratic responses (P < 0.05) for FCR from 1 to 7 d, BWG from 22 to 35 d, and for both responses from 8 to 21 d and 36 to 42 d, as well as in the overall period of 42 days. Carcass and breast yields presented a quadratic improvement (P < 0.01) with increasing Zn-L-SeMet supplementation and Se requirements were estimated at 0.85 and 0.86 ppm, respectively. In the overall period, estimates of Se requirements were 0.64 ppm for BWG and 0.67 ppm for FCR. White striping and WB scores presented quadratic increases (P < 0.01), and maximum scores were observed at 0.68 and 0.67 ppm, respectively. Broilers fed diets formulated without Se supplementation had a higher percentage of normal fillets compared to other Se supplementation levels (quadratic, P < 0.05). In conclusion, increasing Se supplementation to reach maximum growth performance led to higher degrees of severity of WS and WB. Selenium requirements determined in the present study were significantly higher than the present commercial recommendations.

Superoxide-hydrogen peroxide (S-HP) imbalance genetically caused by a gene polymorphism in the human manganese superoxide dismutase enzyme (Val16Ala-MnSOD) is associated with several diseases. Into mitochondria, MnSOD catalyses superoxide radical producing HP and oxygen. Ala-MnSOD genotype presents a high MnSOD efficiency and generates the highest HP concentrations that has been associated with the risk of several cancer types. Cellular selenoenzymes glutathione peroxidase and thioredoxin reductase (TrxR) and catalase (CAT) are essential to HP removal produced in excess in cells. Since, synthesis and activities of selenoenzymes are selenium dependent, we hypothesized that AA-MnSOD cells could have an improvement on antioxidant status undergoing Seleno-L-methionine (SeMet) treatment. This study performed an in vitro protocol to evaluate the response of peripheral blood mononuclear cells (PBMC) carriers of different Val16Ala-MnSOD genotypes exposed to SeMet. SeMet effects on cell viability, apoptosis induction and modulation of oxidative variables were determined using spectrophotometric, flow cytometry, fluorimetric and immunoassays. Gene modulation of antioxidant enzymes was also performed by qRT-PCR. From an initial protocol using heterozygous (AV) cells was determined that 1nM SeMet presented a cytoprotective effect. However, whereas this concentration did not change AA viability, in VV cells it was cytotoxic by increasing necrosis events. SeMet induced higher selenoenzymes levels in AA and VV cells and decreased oxidative markers levels including DNA damage. The results suggest a pharmacogenetic positive response of SeMet effect on AA-cells. Future studies in vivo could be essential to evaluate the potential clinical impact of S-HP imbalance after use of foods or supplements containing SeMet., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Most species of sturgeon have experienced significant population declines and poor recruitment over the past decades, leading many, including white sturgeon (Acipenser transmontanus), to be listed as endangered. Reasons for these declines are not yet fully understood but benthic lifestyle, longevity, and delayed sexual maturation likely render sturgeon particularly susceptible to factors such as habitat alteration and contaminant exposures. One contaminant of particular concern to white sturgeon is selenium (Se), especially in its more bioavailable form selenomethionine (SeMet), as it is known to efficiently bioaccumulate in prey items of this species. Studies have shown white sturgeon to be among the most sensitive species of fish to dietary SeMet as well as other pollutants such as metals, dioxin-like chemicals and endocrine disrupters. One of the primary hypothesized mechanisms of toxicity of SeMet in fish is oxidative stress; however, little is know about the specific mode by which SeMet affects the health of white sturgeon. Therefore, the aim of this study was to characterize oxidative stress and associated antioxidant responses as a molecular event of toxicity, and to link it with the pathological effects observed previously. Specifically, three-year-old white sturgeon were exposed for 72 days via their diet to 1.4, 5.6, 22.4 or 104.4µg Se per g feed (dm). Doses were chosen to range over a necessary Se intake level, current environmentally relevant intakes and an intake representing predicted increases of Se release. Lipid hydroperoxides, which are end products of lipid oxidation, were quantified as a marker of oxidative stress. Changes in gene expression of glutathione peroxidase (GPx), superoxide dismutase, catalase, glutathione S-transferase, apoptosis inducing factor and caspase 3 were quantified as markers of the response to oxidative stress. Concentrations of lipid hydroperoxides were highly variable within dose groups and no dose response was observed. GPx expression was significantly increased in the low dose group indicating an induced antioxidant response. Expression of other genes were not significantly induced or suppressed. Overall, there was very little evidence of oxidative stress, and therefore, in contrast to previous reports on other species of teleost fishes, oxidative stress is not believed to be a main driver of toxicity in white sturgeon exposed to SeMet., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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 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.)

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: A genetic variant at codon 200 (Pro200Leu) of the gene encoding for glutathione peroxidase 1 (GPx1), a selenium-dependent enzyme, is associated with lower enzyme activity; however, the evidence is limited to in vitro and observational studies., Objective: The objective was to determine whether the GPx1 Pro200Leu genetic variants modify the response of whole-blood glutathione peroxidase (GPx) activity to selenium supplementation in patients with coronary artery disease in New Zealand., Design: The results from 2 parallel-design, double-blind trials were combined. Participants were randomly assigned to receive a daily supplement of 100 μg Se as l-selenomethionine (n = 129) or placebo (n = 126) for 12 wk. Plasma selenium and whole-blood GPx activity were measured at baseline and at week 12. Participants were genotyped for the GPx1 Pro200Leu polymorphism., Results: Selenium supplementation increased whole-blood GPx activity by 5 (95% CI: 4, 7) U/g hemoglobin (P < 0.001); however, the magnitude of the increase did not differ by genotype (P = 0.165 for treatment-by-genotype interaction). In an exploratory analysis, a significant nutrient-gene interaction was apparent when baseline plasma selenium concentrations were included in the regression model (P = 0.006 for treatment-by-genotype × baseline selenium concentration interaction). Increases in GPx activity were 2-fold higher in Pro homozygotes than in participants carrying a Leu allele when baseline selenium concentrations were ≤1.15 μmol/L (P < 0.05)., Conclusions: These results indicate that GPx1 Pro200Leu variants do not substantially modify the response of whole-blood GPx to selenium supplementation in individuals with relatively high plasma selenium concentrations. A nutrient-gene interaction was observed when the baseline selenium concentration was low, but this requires independent confirmation. This trial was registered at www.actr.org.au as ACTRN12605000412639 and ACTRN12606000197538.

In total, 180 Lingnan Yellow broiler breeders were used to investigate the effect of different sources of selenium (Se) on the expression of cellular glutathione peroxidase (GPx1) and cytoplasmic thioredoxin reductase (TrxR1) in the liver and kidney of broiler breeders and their offspring by quantitative real-time PCR. There were 6 replicates of 3 dietary treatments. Broiler breeders were fed corn-soy-based diets supplemented with 0.15 mg/kg of Se from sodium selenite, Se-enriched yeast (SY), or selenomethionine (SM). At the end of the feeding trial, liver and kidney mRNA levels of GPx1 and TrxR1 were determined by quantitative real-time PCR, as well as the activity of GPx1 and TrxR1 in liver and kidney of breeders and their offspring. The results showed that, compared with sodium selenite, SY or SM significantly increased (P < 0.05) the activity of TrxR1 in the liver and kidney of broiler breeders and their offspring but not the GPx1 activity. The liver GPx1 and TrxR1 mRNA levels in SY or SM groups were higher (P < 0.05) than that in the sodium selenite group. And the kidney TrxR1 mRNA levels were also significantly increased (P < 0.05) by using SY or SM, whereas there was no significant difference in the kidney GPx1 mRNA levels between the organic or inorganic sources of Se used.

The regulation of site-specific DNA methylation of tumor suppressor genes has been considered as a leading mechanism by which certain nutrients exert their anticancer property. This study was to investigate whether selenium (Se) affects the methylation of globe genomic DNA and the exon-specific p53 gene. Three groups of rats (n = 6-7/group) were fed the AIN-93G basal diet supplemented with 0 [Se deficient (D)], 0.15 [Se adequate (A)], or 4 mg [Se supranutritional (S)] (Se as l-selenomethionine)/kg diet for 104 d, respectively. Rats fed the A or S diet had greater plasma and liver glutathione peroxidase activity, liver thioredoxin reductase activity, and plasma homocysteine concentration than those fed the D diet. However, compared with the A diet, rats fed the S diet did not further increase these Se-dependent enzyme activities or homocysteine concentration. In contrast, Se concentrations in kidney, liver, gastrocnemius muscle, and plasma were increased in a Se-dose-dependent manner. Interestingly, rats fed the S diet had significantly less global liver genomic DNA methylation than those fed the D diet. However, the S diet significantly increased the methylation of the p53 gene (exons 5-8) but not the β-actin gene (exons 2-3) DNA in liver and colon mucosa compared with those fed the D diet. Taken together, long-term Se consumption not only affects selenoprotein enzyme activities, homocysteine, tissue Se concentrations, and global genomic DNA methylation but also increases exon-specific DNA methylation of the p53 gene in a Se-dose-dependent manner in rat liver and colon mucosa.

Background: Selenium, a potential cancer prevention agent currently being tested against prostate cancer in the Selenium and Vitamin E Cancer Prevention Trial (SELECT), plays an integral role in thyroid metabolism. The effects of long-term selenium supplementation on thyroid hormone concentrations are unknown., Objective: The objective was to investigate the effects of long-term selenium supplementation on thyroid hormone concentrations., Design: Twenty-eight healthy adults took 200 microg selenomethionine/d for 28 mo. The thyroid hormones triiodothyronine (T3), thyroxine (T4), and thyrotropin (TSH) were measured in plasma for 4 mo before supplementation and quarterly during supplementation. The assay methods were changed midstudy; the results of the 2 methods were not comparable. Therefore, one analysis was conducted based on the results of the first method, and a second analysis was based on all of the data, adjusted for the change. Serial data collection permitted a test for trends rather than simply a difference between initial and final values., Results: By 9 mo, mean (+/-SEM) plasma selenium concentrations had increased from 1.78 +/- 0.07 micromol/L at baseline to 2.85 +/- 0.11 micromol/L for men and from 1.64 +/- 0.04 to 3.32 +/- 0.1.2 micromol/L for women. T3 concentrations in men increased 5% per year (P = 0.01). T4 and TSH concentrations were unchanged., Conclusions: Selenium supplementation produced no clinically significant changes in thyroid hormone concentrations. A small but statistically significant increase in T3 concentrations was noted in men, with no corresponding decreases in TSH. A subset of SELECT subjects might be monitored periodically for changes during long-term selenium supplementation.

Background: Brazil nuts provide a rich natural source of selenium, yet no studies have investigated the bioavailability of selenium in humans., Objective: We investigated the efficacy of Brazil nuts in increasing selenium status in comparison with selenomethionine., Design: A randomized controlled trial was conducted with 59 New Zealand adults. Participants consumed 2 Brazil nuts thought to provide approximately 100 mug Se, 100 mug Se as selenomethionine, or placebo daily for 12 wk. Actual intake from nuts averaged 53 mug Se/d (possible range: 20-84 mug Se). Plasma selenium and plasma and whole blood glutathione peroxidase (GPx) activities were measured at baseline and at 2, 4, 8, and 12 wk, and effects of treatments were compared., Results: Plasma selenium increased by 64.2%, 61.0%, and 7.6%; plasma GPx by 8.3%, 3.4%, and -1.2%; and whole blood GPx by 13.2%, 5.3%, and 1.9% in the Brazil nut, selenomethionine, and placebo groups, respectively. Change over time at 12 wk in plasma selenium (P < 0.0001 for both groups) and plasma GPx activity in the Brazil nut (P < 0.001) and selenomethionine (P = 0.014) groups differed significantly from the placebo group but not from each other. The change in whole blood GPx activity was greater in the Brazil nut group than in the placebo (P = 0.002) and selenomethionine (P = 0.032) groups., Conclusion: Consumption of 2 Brazil nuts daily is as effective for increasing selenium status and enhancing GPx activity as 100 mug Se as selenomethionine. Inclusion of this high-selenium food in the diet could avoid the need for fortification or supplements to improve the selenium status of New Zealanders.

The molecular basis and downstream targets of oral selenium supplementation in individuals with elevated risk of cancer due to chronic exposure from environmental carcinogens has been largely unexplored. In this study, we investigated genome-wide differential gene expression in peripheral blood mononuclear cells (PBMC) from individuals with pre-malignant arsenic (As)-induced skin lesions before and after 6 months daily oral supplementation of 200 microg L-selenomethionine. The Affymetrix GeneChip Human 133A 2.0 array, containing probes for 22,277 gene transcripts, was used to assess gene expression. Three different normalization methods, RMA (robust multi-chip analysis), GC-RMA and PLIER (Probe logarithmic intensity error), were applied to explore differentially expressed genes. We identified a list of 28 biologically meaningful, significantly differentially expressed genes. Genes up-regulated by selenium supplementation included TNF, IL1B, IL8, SOD2, CXCL2 and several other immunological and oxidative stress-related genes. When mapped to a biological association network, many of the differentially expressed genes were found to regulate functional classes such as fibroblast growth factor, collagenase, matrix metalloproteinase and stromelysin-1, and thus, considered to affect cellular processes like apoptosis, proliferation and others. Many of the significantly up-regulated genes following selenium-supplementation were previously found by us to be down-regulated in a different set of individuals with As-induced skin lesions compared to those without. In conclusion, findings from this study may elucidate the biological effect of selenium supplementation in humans. Additionally, this study suggests that long-term selenium supplementation may revert some of the gene expression changes presumably induced by chronic As exposure in individuals with pre-malignant skin lesions.

Selenium (Se) is an essential nutrient for humans and animals. The Se RDA for adult humans is 55 mug/d; however, dietary amounts as high as 200 mug/d in the highly available form of selenomethionine in yeast were shown to reduce the incidence of certain cancers. A number of natural foods contain relatively high amounts of Se; for the most part, however, the availability of food Se for absorption and utilization is unknown. This experiment was conducted to determine the bioavailability of Se from a high-protein, high-fiber bran-isolate of buckwheat groats that contains Se. The method used was based on the ability of Se from buckwheat bran to restore Se-dependent enzyme activities and tissue Se concentrations in Se-deficient rats. The responses produced from buckwheat bran Se were compared with a standard response curve generated by feeding graded amounts of Se as sodium selenite (Na(2)SeO(3); Na selenite) or selenomethionine (SeMet) in a newly reformulated AIN-93G-Torula yeast diet with a more balanced nutrient composition than older diets of this nature. Relative bioavailability was determined by using the slope-ratio assay method for enzyme data, or the parallel lines assay method for tissue Se concentration data. Results showed that Se availability from buckwheat bran based on the restoration of plasma Se was 70-80% as high as Na selenite or SeMet. However, when based on the restoration of muscle Se, buckwheat bran was 90% as high as Na selenite, but only 60% as high as SeMet. When using the ability of dietary Se to restore whole blood and liver glutathione peroxidase activity, buckwheat bran Se was 75-80% as high as Na selenite or SeMet. However, for the restoration of liver thioredoxin reductase, buckwheat bran Se was only 40% as high as Na selenite and 70% as high as SeMet. The relative bioavailability of Se from buckwheat bran with all variables considered was approximately 73% whether measured against Na selenite or SeMet. Although some variables indicated low bioavailability of Se from buckwheat bran, other factors such as Se speciation in the bran, digestibility of the bran, the cooking process, and combinations with other foods in the diet should be considered and analyzed before firm conclusions can be reached.

Limited therapeutic selectivity and tumor resistance are major obstacles to current chemotherapy. The development of new therapeutic modalities for solid tumor remains a challenge. The use of selenium, 5-methylselenocysteine (MSC), or seleno-L-methionine (SLM) as selective modulators of anticancer drugs is novel and has not been previously investigated. Selenium deficiency is associated with an increased risk of cancer and cancer death. Although low-dose selenium supplementation has been investigated in a large randomized prevention trial, its potential in chemotherapy toxicity prevention and enhancement of antitumor activity of anticancer drugs has not been evaluated. An ideal biomodulator of anticancer drugs would allow escalation of drug dose with the hope of enhancing antitumor activity and possibly reversing drug resistance. Results from this laboratory have demonstrated that MSC and SLM are highly effective modulators of irinotecan cure rates in de novo sensitive and resistant human tumor xenografts. Studies in mice have documented that the minimum effective dose of MSC when combined with irinotecan is 0.01 mg daily. The optimal schedule is to administer MSC orally for 7 days before and concurrently with irinotecan. The observed effects were not drug-specific, as similar results were obtained with taxanes, platinum agents, 5-fluorouracil, and anthracyclines; nor were they species-specific, as selective effects were obtained in mice and rats and are currently being confirmed in ongoing clinical trials.

Research has shown that trace elements, such as Se, Mn, and Zn, can alter reproductive functions. The aim of the current study was to evaluate the sperm quality index (SQI) and sperm viability as affected by various levels and sources of Se, Mn, and Zn when added in vitro to broiler breeder semen. In vitro treatments consisted of the following sources and levels of minerals: Control, no minerals added to sperm; seleno L-methionine, 4 levels ranging from 8.78 to 7,896 microg/L; sodium selenite, 4 levels ranging from 8.78 to 7,896 microg/L; MnSO4, 8 levels ranging from 6,500 to 65,000 mg/L; Zn 180 (Zinpro Corporation), 4 levels ranging from 0.65 to 650 mg/L; and ZnSO4, 4 levels ranging from 0.65 to 650 mg/L. The addition of 7,896 microg of sodium selenite/L to semen was detrimental to sperm motility. Also, MnSO4 adversely affected SQI and sperm viability at concentrations of 6,500 mg/L and greater. Sperm viability was decreased when 650 mg/L of Zn 180 was added to semen. Sperm motility was depressed by exposure to Zn 180 at 650 mg/L and ZnSO4 at 65 and 650 mg/L. Our results suggest that these trace minerals must act at the reproductive tissue level during spermatogenesis to improve semen quality. Direct in vitro application of these elements to semen appears to be detrimental to spermatozoa.

Brain function and selenium concentration are well maintained in rodents under conditions of selenium deficiency. Recently, however, targeted deletion of the selenoprotein P gene (Sepp) has been associated with a decrease in brain selenium concentration and with neurological dysfunction. Studies were conducted with Sepp(-/-) and Sepp(+/+) mice to characterize the neurological dysfunction and to correlate it with dietary selenium level. When weanling Sepp(-/-) mice were fed the basal diet (<0.01 mg/kg selenium) supplemented with 0, 0.05 or 0.10 mg selenium/kg, they developed spasticity that progressed and required euthanasia. Supplementing the diet with > or =0.25 mg selenium/kg prevented the neurological dysfunction. To determine whether neurological dysfunction would occur in more mature Sepp(-/-) mice deprived of selenium, Sepp(-/-) mice that had been fed the basal diet supplemented with 1.0 mg selenium/kg for 4 wk were switched to a selenium-deficient diet. Within 3 wk they had developed neurological dysfunction and weight loss. At 3 wk, the 1.0 mg selenium/kg diet was reinstituted. Neurological function stabilized but did not return to normal. Brain selenium concentration did not increase. Weight gain resumed. This study shows that neurological dysfunction occurs when selenium supply to the brain is curtailed and that the dysfunction is not readily reversible. Both the absence of selenoprotein P and a low dietary selenium supply are necessary for the dysfunction to occur, indicating that selenoprotein P and at least one other form of selenium supply the element to the brain.

Background: Oxidative stress, as measured by 8-iso-prostaglandin F(2)(alpha) (8-iso-PGF(2)(alpha)), and depleted antioxidant defenses were shown in stable cystic fibrosis (CF) patients. The plasma fatty acid status of CF patients was linked to oxidative stress after respiratory exacerbations., Objective: We examined changes in plasma 8-iso-PGF(2)(alpha), antioxidant defenses, plasma fatty acid status, and clinical markers resulting from short-term antioxidant supplementation., Design: Forty-six CF patients were randomly assigned to either group A [low dose of supplement (10 mg vitamin E and 500 micro g vitamin A)] or group B [high dose of supplement (200 mg vitamin E, 300 mg vitamin C, 25 mg beta-carotene, 90 micro g Se, and 500 micro g vitamin A)]. Plasma concentrations of 8-iso-PGF(2)(alpha), vitamins E and C, beta-carotene, zinc, selenium, and copper; plasma fatty acid composition; erythrocyte glutathione peroxidase (EC 1.11.1.9) and superoxide dismutase (EC 1.15.1.1) activities; lung function; and dietary intake were measured before and after 8 wk of supplementation., Results: Antioxidant defenses in group B improved, whereas those in group A did not: in groups B and A, the mean (+/- SEM) changes (Delta) in vitamin E were 10.6 +/- 1.5 and -1.9 +/- 0.9 micro mol/L, respectively (P < 0.001), (Delta)beta-carotene were 0.1 +/- 0.04 and -0.01 +/- 0.02 micro mol/L, respectively (P = 0.007), (Delta)selenium were 0.51 +/- 0.10 and -0.09 +/- 0.04 micro mol/L, respectively (P < 0.001), and (Delta)glutathione peroxidase activity were 1.3 +/- 0.3 and -0.3 +/- 0.6 U/g hemoglobin, respectively (P = 0.016). There were no significant differences between the groups in Delta8-iso-PGF(2)(alpha), (Delta)vitamin C, (Delta)fatty acid composition, (Delta)superoxide dismutase activity, (Delta)lung function, or (Delta)white cell count. Within group B, (Delta)beta-carotene correlated with (Delta)percentage of forced vital capacity (r = 0.586, P = 0.005), (Delta)selenium correlated with (Delta)percentage of forced expiratory volume in 1 s (r = 0.440, P = 0.046), and (Delta)plasma fatty acid concentrations correlated with (Delta)percentage of forced expiratory volume in 1 s (r = 0.583, P = 0.006) and Delta8-iso-PGF(2)(alpha) (r = 0.538, P = 0.010)., Conclusions: Whereas increased beta-carotene, selenium, and fatty acid concentrations are linked to improved lung function, increased plasma fatty acid concentrations are linked to oxidative stress. If oxidative stress is deemed to be important to the clinical outcome of CF patients, means of reducing oxidative stress while maintaining a high-fat, high-energy diet must be investigated.

Human evidence indicates fetotoxicity of methylmercury at exposure levels inducing only slight and reversible maternal toxicity, but experimental animal data demonstrate, that fetotoxicity may occur despite absence of noticeable maternal toxicity. However, in contrast to the long-term exposure in humans, the key point in the experimental design of the majority of experimental studies has been administration of few doses of methylmercury late in gestation. The present study in mice therefore used long-term maternal exposure to methylmercury (1 nmol/ml in drinking water) and a cross-fostering design to investigate separately in different offsprings the toxicokinetics of transplacentally absorbed mercury and mercury retained during lactation. Further, the influence of seleno-L-methionine (3 micrograms/ml in drinking water) on the toxicokinetics of methylmercury in these mice was studied. The present study demonstrated, that independent on seleno-L-methionine supplementation, offspring deposited equal amounts of mercury during lactation and during gestation. Moreover, the organ distribution and rate of excretion of mercury in transplacentally exposed mice were considerably different from those in mice exposed postnatally and from adult mice in studies using comparable dosages. Seleno-L-methionine only slightly affected the toxicokinetics of mercury in offspring.

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.

We investigated the incorporation of Se into the proteins of liver and muscle, the two main Se pools, during replenishment of Se-deficient rats with normal or large doses of 75Se-labeled selenite and selenomethionine, doses equivalent to the amounts ingested from a diet with 0.2 or 2 mg Se/kg. With the higher intake, Se levels were elevated. More Se was retained from selenomethionine than from selenite. After separation of the labeled proteins, it was apparent that the higher tissue Se contents were mainly due to nonspecific incorporation into a large number of proteins. We observed no differences between the two chemical forms with regard to the formation of the specific selenoproteins. The 10-fold increase in the Se supply led to a relatively small rise in the levels of these compounds. The results indicate that after ingestion of normal amounts of selenite nearly all of the element is present in the specific selenoproteins. With increasing doses a part is also incorporated nonspecifically into numerous other proteins. In the case of selenomethionine, a part of the element follows the same metabolic pathways, but a percentage is also deposited directly and nonspecifically into proteins in place of methionine.

Three groups of 11 New Zealand women each received, for 32 wk, yeast tablets with no added selenium (placebo) or 200 micrograms Se/d in tablets either as selenate or as selenium-enriched yeast (SeMet) in a double-blind selenium trial. Plasma and erythrocyte (RBC) samples were collected bimonthly. Gel filtration of plasma from women taking SeMet revealed two major selenium-containing peaks with most of the selenium in the second peak. In contrast, the first peak contained most of the selenium in plasma from women taking selenate. Chromatography of RBC lysates indicated that the majority of the selenium was with hemoglobin (Hb) in women taking SeMet but was about equally distributed between glutathione peroxidase (GSH-Px) and Hb in women taking selenate. The percentage of selenium associated with GSH-Px was found to be greater in RBCs and plasma of women taking selenate than of those taking SeMet.

Two experiments were conducted to determine the effect of various forms of selenium (Se) on the activity of glutathione peroxidase (GSHPx) in liver, heart, kidney and eyes of the developing rat. In experiment 1, throughout mating, pregnancy and lactation, female rats consumed one of three diets: basal (less than 0.05 microgram Se/g); selenite (0.15 microgram Se/g) and selenomethionine (0.15 microgram Se/g). Some pups born to dams in the basal group were also given intraperitoneal doses of saline, selenite or selenomethionine. GSHPx activity was measured in tissues from fetuses, 7-d-old and 14-d-old nursing pups and the dams. In all tissues studied, GSHPx activity was highest in the 14-d-old pups whose mothers were in the selenomethionine group. Rat pups given intraperitoneal selenite (3 micrograms/kg body weight) had higher liver and kidney GSHPx activity than pups given the same amount of selenium as intraperitoneal selenomethionine. In experiment 2, all dams were fed the same basal diet, and pups were weaned to diets containing one of two levels of selenium (0.1 or 0.2 microgram/g), one of three forms of selenium (selenite, selenomethionine or selenocystine) or no added selenium. After 14 d of repletion, the highest level of hepatic GSHPx activity occurred in the selenite group and the lowest in the basal diet group. After 21 d of repletion, renal GSHPx activity was lowest in the basal group followed by the selenocystine group. The highest tissue selenium concentration was found in kidney tissues of the selenocystine group. These data support the hypothesis that these dietary forms of selenium are differentially available for GSHPx activity.

A stable (nonradioactive) isotope of selenium in a chemical form common in foods (selenomethionine) or inorganic selenite was taken orally (200 micrograms/d) for 3 wk to label deep body pools. By deep body pools we mean selenium compartments that are large and/or have a slow turnover (exchange) rate. Blood plasma was removed, stored for 11 mo, and later reinfused as a labeled tracer dose with the selenium label in all of the biologically significant chemical forms. Accessible tissues such as red blood cells were highly labeled (20-25%) in the subjects receiving selenomethionine. Selenium from deep body pools is excreted primarily via the urine (80%). Reexcretion of previously absorbed selenium back into the gastrointestinal tract can be measured, avoiding a major source of error in conventional balance studies used to estimate nutrient absorption.

Selenium (Se) toxicity is known to be affected by level of intake of the mineral, but there are conflicting reports on the relative toxicities of the various chemical forms of Se. We monitored Se toxicity in rats fed Torula yeast-based diets containing 0.1, 0.5 or 2.5 micrograms Se/g of diet as either sodium selenate (Na2SeO4) or L-selenomethionine (SeMet). Half the diets were supplemented to contain adequate dietary methionine (Met). Weights were monitored weekly for 6 (Met-adequate) or 7 (Met-deficient) wk, at which time the rats were killed. There were no significant differences in final weight among Met-adequate rats, regardless of level or form of dietary Se. Methionine-deficient rats all gained significantly less weight than their Met-adequate counterparts. Selenosis was most severe in the Met-deficient rats fed 2.5 micrograms Se/g of diet as Na2SeO4, as indicated by significantly impaired weight gains. Nonetheless, Se retention in serum, heart, brain, bone, testes, colon, skin, lungs and pancreas was greater in rats fed SeMet than in those fed Na2SeO4, and Met deficiency further intensified this trend. The kidney was the only organ in which Se levels were markedly higher in the severely poisoned Met-deficient rats fed Na2SeO4. Further research is needed to determine whether elevated kidney Se levels are related to the greater toxicity observed in the Met-deficient rats fed Na2SeO4.

Experiments were conducted to determine the effects of dietary protein level and level of feed intake on the apparent bioavailability of Se from Na2SeO3 and selenomethionine (DL-Se-Met) for protection from exudative diathesis (ED) of the Se- and vitamin E-depleted chick. Level of dietary protein (22.5 vs. 16.9%) significantly (P less than .01) affected the incidence of ED at several levels of dietary Se from each source. At each level of Se, the low protein diet resulted in a lower incidence of ED and, thus, an increase in the apparent bioavailability of Se; Se from Na2SeO3 was more available than that from Se-Met. Further experiments were conducted to determine whether the effect of dietary protein level on the incidence of ED was due to effects on growth rate or feed intake. Chicks were fed the high or low protein basal diets at 75% of ad libitum rate of feed consumption. Sodium selenite was added to make Se intakes equivalent, either on a per day or a per unit gain basis, to ad libitum feeding controls receiving the Se-supplemented diets. Results showed that both a low level of dietary protein and a restricted level of feeding markedly reduced the incidence and severity of ED. The activity of Se-dependent glutathione peroxidase (SeGSHpx) in plasma and liver varied inversely with the incidence of ED and was increased by feed restriction. These results suggest that growth rate affects both the clinical and biochemical manifestations of Se-deficiency in the chick. Because both parameters are used to assess the bioavailability of Se in feeds and foods, bioassays in which growth rate is different between test and reference treatments may yield incorrect results.

Lower renal plasma clearances of selenium (CSe 0.1-0.2 ml min-1), indicating excretion of a smaller proportion of Se presented to the kidneys, were found in New Zealand (NZ) residents with low plasma Se ((Se)p 50-70 ng ml-1) on customary intakes below 30 micrograms d-1 Se. North American subjects consuming 80 micrograms d-1 with (Se)p 120-140 ng ml-1 had CSe between 0.2 and 0.3 ml min-1. Several weeks' supplementation with high-Se bread increased NZ subjects' (Se)p to 120-175 ng ml-1 and CSe to 0.4-0.7 ml min-1. (Se)p remained elevated when supplementation ceased, but CSe returned to the basal range within a few days. Americans' clearances showed no such abrupt decrease when their dietary intake was similarly reduced. The NZ residents thus appeared to excrete selenium more sparingly than others. Rapid alterations in clearance after supplements and single doses were probably due to changes in the proportions of different forms of selenium in the plasma.

An experiment was designed to determine if surgical bursectomy (Bx) of day-old chicks would alter the distribution or amount of selenium (Se) in chicken tissues. Sham-operated chicks and Bx chicks were fed a practical corn-soy diet with either no supplemented Se, selenite to supply .1 ppm Se, or selenomethionine to supply .1 ppm Se. Several chicks were killed at 10 and 21 days of age to determine tissue Se levels. At each time the remaining chicks were injected with sheep red blood cells (SRBC). The remaining chickens were killed at 56 days. Serum from Bx chicks caused no agglutination with SRBC, and the immunoglobulin content was decreased as compared to levels in serum of sham-operated chicks. The Se level of tissues increased as a result of time and Se supplementation (P less than .01). The Bx caused a small but significant (P less than .01) decrease in spleen Se level, but other tissue Se levels were not affected. The results suggest that the serum lymphocytes and immunoglobulins have only a passive function in Se metabolism and distribution in chickens.