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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.)

Background: Selenium (Se) is a rare essential element that plays a vital role in the health and performance of animals. By interfering in the production of antioxidant enzymes such as glutathione peroxidase, thioredoxin reductase and methionine sulfoxide, Se plays a role in reducing the effects of oxidative stress and animal performance., Objectives: This study aimed to investigate the effect of hydroxy-selenomethionine (OH-SeMet) in the diet of broiler breeder and old broiler breeder roosters on productive performance, reproduction and sperm quality parameters., Methods: For this purpose, 260 broiler breeders of the Ross 308 strain were used in a completely randomized design with four treatments and five replications (13 hens and one rooster in each replication). Experimental treatments included: (1) a basal diet without OH-SeMet (T1:control), (2) a broiler breeder diet without OH-SeMet and a rooster diet containing 0.1 mg/kg OH-SeMet (T2), (3) broiler breeder diet containing 0.1 mg/kg OH-SeMet and rooster diet without OH-SeMet (T3) and (4) broiler breeder and rooster diet contained 0.1 mg/kg OH-SeMet (T4)., Results: The results showed that T3 and T4 treatments improved egg production, egg weight, egg mass and feed conversion ratio (FCR) compared to the control treatment (p < 0.05). The fertility and hatchability percentages of T4 and T2 treatments increased compared to T1 and T3 treatments (p < 0.05). The rate of embryonic losses in T1 was higher than in other treatments. However, grade one chickens were higher in T4 than in other treatments (p < 0.05). Total motility and viability of sperms were significantly higher in T2 and T4 treatments than in T1 and T3 treatments. The sperm abnormality percentage and sperm MDA concentration decreased in T2 and T4 treatments., Conclusions: Therefore, using OH-SeMet may be a practical approach to help old broiler breeders' production and reproduction performance., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Heat stress is the most common environmental stressor in poultry production, negatively affecting growth performance, meat quality, and welfare. Therefore, the aim of this study was to compare the nutritional effects of dietary supplementation with selenomethionine, Bacillus subtilis (BS), and a combination of selenomethionine and BS on broilers challenged with heat stress. A total of 300 21-day-old male broilers (Ross 308) were randomly assigned to 5 groups with 6 replicates of 10 broilers per each: control group (CON, broilers raised at 22 ± 2 °C), heat stress exposure group (HS, broilers raised at 32 ± 2 °C for 8 h/d), HSS group (HS group supplemented with 0.3 mg/kg selenomethionine), HSB group (HS group supplemented with 1 × 109 cfu/kg BS), and HSBS group (HS group supplemented with 0.3 mg/kg selenomethionine and × 109 cfu/kg BS). The experiment lasted for 21 d. The results indicated that, compared to the CON group, heat stress reduces (P < 0.05) broiler growth performance and damages the meat quality in breast and thigh muscles. Dietary supplementation with selenomethionine and BS did not improve the growth performance of broilers under heat stress. However, compared to the HS group, the HSS, HSB, and HSBS groups showed significantly increased (P < 0.05) pH45 min, redness (a*) and yellowness (b*), muscle fiber density, intramuscular fat, triglyceride content, and expression levels of Myf5, CAPN 2, FM, SLC27A1, A-FABP, H-FABP, APOB-100, and ACC in breast and thigh muscles. Meanwhile, these groups showed reduced (P < 0.05) lightness (L*), drip loss, shear force, muscle fiber cross-sectional area, and FM gene expression level. The HSBS group showed greater improvement in the physicochemical quality of muscle and volatile substances compared to the HSS and HSB groups. In conclusion, selenomethionine and BS improved meat quality and flavor in broilers under heat stress by modulating muscle fiber composition and characteristics, as well as increasing intramuscular fat deposition., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Previously, insulin resistance and hepatic oxidative stress with increased expressions of glutathione peroxidase (GPx) 1 and selenoprotein P (SelP) were induced in NSY mice, a diabetic mouse model, by administrating a high fat diet (HFD) and seleno-L-methionine (SeMet) for 12 weeks. In this study we developed an analysis method for serum selenoproteins using LC-tandem mass spectrometry (LC-MS/MS) and investigated the effects of supplementary selenium on serum concentrations of selenoproteins as well as protein expression in skeletal muscle as a major insulin target tissue under the same experimental condition. The glucose area under the curves for oral glucose tolerance and insulin tolerance tests indicated that the HFD induced insulin resistance, whereas the treatment of SeMet + HFD showed insignificant promotion compared with the HFD-induced insulin resistance. Although the expressions of GPx1 in gastrocnemius and soleus were not significantly induced by supplementary SeMet nor HFD administration, the expressions of SelP in both skeletal muscles were significantly induced by the treatment of SeMet + HFD. There were also significant increases in serum concentrations of SelP by supplementary SeMet + HFD administration, whereas GPx3 was augmented by supplementary SeMet only. These results indicated that the HFD intake under the sufficient selenium status augmented the blood secretion of SelP, which may participate in the reduction of insulin sensitivity in skeletal muscles as well as liver or adipose tissues, and it is a better indicator of deterioration than GPx3 as it is a major selenoprotein in serum.

Cow's milk allergy is a common food allergy in infants, and is associated with an increased risk of developing other allergic diseases. Dietary selenium (Se), one of the essential micronutrients for humans and animals, is an important bioelement which can influence both innate and adaptive immune responses. However, the effects of Se on food allergy are still largely unknown. In the current study it was investigated whether dietary Se supplementation can inhibit whey-induced food allergy in an animal research model. Three-week-old female C3H/HeOuJ mice were intragastrically sensitized with whey protein and cholera toxin and randomly assigned to receive a control, low, medium or high Se diet. Acute allergic symptoms, allergen specific immunoglobulin (Ig) E levels and mast cell degranulation were determined upon whey challenge. Body temperature was significantly higher in mice that received the medium Se diet 60 min after the oral challenge with whey compared to the positive control group, which is indicative of impaired anaphylaxis. This was accompanied by reductions in antigen-specific immunoglobulins and reduced levels of mouse mast cell protease-1 (mMCP-1). This study demonstrates that oral Se supplementation may modulate allergic responses to whey by decreasing specific antibody responses and mMCP-1 release.

Background: T-2 toxin is a mycotoxin produced by Fusarium species that is highly toxic to animals. Recent studies have indicated that Selenomethionine (SeMet) have protective effect against mycotoxins-induced toxicity. The aim of the present study was to investigate the protective effect of SeMet on T-2-toxin-induced liver injury in rabbit and explore its molecular mechanism. Fifty rabbits (30 d, 0.5 ± 0.1 kg) were randomly divided into 5 groups: control group, T-2 toxin group, low, medium and high dose SeMet treatment group. The SeMet-treated group was orally pretreated with SeMet (containing selenium 0.2 mg/kg, 0.4 mg/kg and 0.6 mg/kg) for 21 days. On the 17th day, T-2 toxin group and SeMet-treated group were orally administered with T-2 toxin (0.4 mg/kg body weight) for 5 consecutive days., Results: The results showed that low-dose SeMet significantly improved T-2 toxin-induced liver injury. We found that low-dose SeMet can reduce the level of oxidative stress and the number of hepatocyte apoptosis. Moreover, the levels of Bax, caspase-3 and caspase-9 were significantly reduced and the levels of Bcl-2 were increased., Conclusions: Therefore, we confirmed that low-dose SeMet may protect rabbit hepatocytes from T-2 toxin by inhibiting the mitochondrial-caspase apoptosis pathway.

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.)

Background: Selenium (Se) is a nutritionally essential trace element and health may be improved by increased Se intake. Previous kinetic studies have shown differences in metabolism of organic vs. inorganic forms of Se [e.g., higher absorption of selenomethionine (SeMet) than selenite (Sel), and more recycling of Se from SeMet than Sel]. However, the effects on Se metabolism after prolonged Se supplementation are not known., Objective: To determine how the metabolism and transport of Se changes in the whole-body in response to Se-supplementation by measuring Se kinetics before and after 2 years of Se supplementation with SeMet., Methods: We compared Se kinetics in humans [n = 31, aged 40 ± 3 y (mean ± SEM)] studied twice after oral tracer administration; initially (PK1), then after supplementation for 2 y with 200 µg/d of Se as selenomethionine (SeMet) (PK2). On each occasion, we administered two stable isotope tracers of Se orally: SeMet, the predominant food form, and selenite (Na 2 76 SeO 3, or Sel), an inorganic form. Plasma and RBC were sampled for 4 mo; urine and feces were collected for the initial 12 d of each period. Samples were analyzed for tracers and total Se by isotope dilution GC-MS. Data were analyzed using a compartmental model, we published previously, to estimate fractional transfer between pools and pool masses in PK2., Results: We report that fractional absorption of SeMet or Sel do not change with SeMet supplementation and the amount of Se absorbed increased. The amount of Se excreted in urine increases but does not account for all the Se absorbed. As a result, there is a net incorporation of SeMet into various body pools. Nine of the 11 plasma pools doubled in PK2; two did not change. Differences in metabolism were observed for SeMet and Sel; RBC uptake increased 247% for SeMet, urinary excretion increased from two plasma pools for Sel and from two different pools for SeMet, and recycling to liver/tissues increased from one plasma pool for Sel and from two others for SeMet. One plasma pool increased more in males than females in PK2., Conclusions: Of 11 Se pools identified kinetically in human plasma, two did not increase in size after SeMet supplementation. These pools may be regulated and important during low Se intake., Competing Interests: JM was employed by the company Information Management Services, Inc., and MW was employed by Metabolic Modeling Services. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Patterson, Combs, Taylor, Patterson, Moler and Wastney.)

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.)

Many bioactive natural compounds are being increasingly used for therapeutics and nutraceutical applications to counteract male infertility, particularly varicocele. The roles of selenium and Polydeoxyribonucleotide (PDRN) were investigated in an experimental model of varicocele, with particular regard to the role of NLRP3 inflammasome. Male rats underwent sham operation and were daily administered with vehicle, seleno-L-methionine (Se), PDRN, and with the association Se-PDRN. Another group of rats were operated for varicocele. After twenty-eight days, sham and varicocele rats were sacrificed and both testes were weighted and analyzed. All the other rats were challenged for one month with the same compounds. In varicocele animals, lower testosterone levels, testes weight, NLRP3 inflammasome, IL-1β and caspase-1 increased gene expression were demonstrated. TUNEL assay showed an increased number of apoptotic cells. Structural and ultrastructural damage to testes was also shown. PDRN alone significantly improved all considered parameters more than Se. The Se-PDRN association significantly improved all morphological parameters, significantly increased testosterone levels, and reduced NLRP3 inflammasome, caspase-1 and IL-1β expression and TUNEL-positive cell numbers. Our results suggest that NLRP3 inflammasome can be considered an interesting target in varicocele and that Se-PDRN may be a new medical approach in support to surgery.

Exercise overproduces oxygen reactive species (ROS) and eventually exceeds the body's antioxidant capacity to neutralize them. The ROS produce damaging effects on the cell membrane and contribute to skeletal muscle damage. Selenium (Se), a natural mineral trace element, is an essential component of selenoproteins that plays an important role in antioxidant defense. The activity of the enzyme glutathione peroxidase (GPx), a highly-efficient antioxidant enzyme, is closely dependent on the presence of Se. These properties of Se may be potentially applicable to improve athletic performance and training recovery. We systematically searched for published studies to evaluate the effectiveness of Se supplementation on antioxidant defense system, muscle performance, hormone response, and athletic performance among physically active individuals. We used the Preferred Reporting Elements for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and searched in SCOPUS, Web of Science (WOS), and PubMed databases to identify published studies until March 2020. The systematic review incorporated original studies with randomized controlled crossover or parallel design in which intake of Se administered once a day was compared with the same placebo conditions. No exclusions were applied for the type of physical exercise performed, the sex, nor the age of the participants. Among 150 articles identified in the search, 6 met the criteria and were included in the systematic review. The methodological quality of the studies was evaluated using the McMaster Critical Review Form. Oral Se supplementation with 180 µg/day or 240 µg/day (selenomethionine) and 200 µg/day (Sodium Selenite), significantly decreased lipid hydroperoxide levels and increased GPx in plasma, erythrocyte, and muscle. No significant effects were observed on athletic performance, testosterone hormone levels, creatine kinase activity, and exercise training-induced adaptations on oxidative enzyme activities or on muscle fiber type myosin heavy chain expression. In addition, Se supplementation showed to have a dampening effect on the mitochondria changes in chronic and acute exercise. In summary, the use of Se supplementation has no benefits on aerobic or anaerobic athletic performance but it may prevent Se deficiencies among athletes with high-intensity and high-volume training. Optimal Se plasma levels may be important to minimize chronic exercise-induced oxidative effects and modulate the exercise effect on mitochondrial changes.

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.)

Selenium (Se) is an essential trace element of concern that is known to contaminate aquatic ecosystems as a consequence of releases from anthropogenic activities. Selenium is of particular toxicological concern for egg-laying vertebrates as they bioaccumulate Se through the diet and deposit excess Se to embryo-offspring via maternal transfer, a process which has been shown to result in significant teratogenic effects. The purpose of the present study was to determine and compare the in ovo effects of Se exposure on early development of a laboratory model fish species native to North American freshwater systems, the fathead minnow (Pimephales promelas), through two different exposure routes, maternal transfer and microinjection. For maternal transfer studies, fathead minnow breeding groups (3 females: 2 males) were exposed to diets containing Se-background levels (1.21 μg Se/g food, dry mass [dm]) or environmentally relevant concentrations of selenomethionine (SeMet; 3.88, 8.75 and 26.5 μg Se/g food dm) and bred for 28 days. Embryos were collected at different time points throughout the study to measure Se concentrations and to assess teratogenicity in embryos. While exposure to dietary Se did not negatively affect fecundity among treatment groups, the lowest treatment group (3.88 μg Se/g food dm) produced on average the most embryos per day, per female. The maternal transfer of excess Se occurred rapidly upon onset of exposure, reaching steady-state after approximately 14 days, and embryo Se concentrations increased in a dose-dependent manner. The greatest concentrations of maternally transferred Se significantly increased the total proportion of deformed embryo-larval fathead minnows but did not impact hatchability or survival. In a second study, fathead minnow embryos were injected with SeMet at concentrations of 0.00 (vehicle control), 9.73, 13.5 and 18.9 μg Se/g embryo dm. Microinjection of SeMet did not affect hatchability but significantly increased the proportion of deformed embryo-larval fish in a dose-dependent manner. There was a greater proportion of deformed fathead minnows at embryo Se concentrations of 18.9 μg Se/g embryo dm when exposed via microinjection versus maternal transfer at concentrations of 28.4 μg Se/g embryo dm. However, the findings suggest that both exposure routes induced analogous developmental toxicities in early life stage fish at Se concentrations between 9.73 and 13.5 μg Se/g embryo dm. Overall, this study demonstrated that microinjection has utility for studying the effects of Se in embryo-larval fish and is a promising method for the study of early life stage Se exposure in egg-laying vertebrates., (Copyright © 2019. Published by Elsevier B.V.)

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.

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.

Selenosis, or selenium toxicosis, occurs in wildlife and livestock, usually because of excessive intake of selenium via selenium-containing plants. Although it is known that wild slider turtles can accumulate large amounts of selenium, little is known about how selenium exposure may affect these reptiles. In this study, the authors report histopathologic changes in yellow-bellied sliders ( Trachemys scripta scripta) caused by experimental exposure to selenomethionine. Microscopic changes in kidney and claw tissue were most significant and resembled those reported in birds. Turtles in the selenium treatment groups had acute tubular degeneration and regeneration in the kidney, with hyaline droplets in the high-dose animals, and changes in the claws ranging from epidermal hyperplasia with disorganization and intercellular edema to ulceration, and accumulation of seroheterophilic exudate between the epidermis and cornified layer. Although selenium burdens in this study are comparable with values found in wild slider turtles, more data are needed to determine if similar histopathologic abnormalities arise in wild animals exposed to high levels of selenium.

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.

This study aimed to evaluate the effect of hydroxy-selenomethionine (HMSeBA), a novel organic selenium (Se) source, on milk performance, antioxidative status, and Se concentrations in the milk and plasma of mid-lactation dairy cows compared with that of sodium selenite (SS). Fifty mid-lactation dairy cows with similar days in milk, milk yield, and parity received the same basal diet containing 0.06 mg of Se/kg of DM. They were assigned to 1 of 5 treatments according to a randomized complete block design: negative control (without Se supplementation), SS supplementation (0.3 mg of Se/kg of DM; SS-0.3) or HMSeBA supplementation (0.1, 0.3, or 0.5 mg of Se/kg of DM: SO-0.1, SO-0.3, and SO-0.5, respectively). The experiment lasted for 10 wk, including a pretrial period of 2 wk. The results indicated that neither Se supplementation nor Se source affected dry matter intake, milk yield, milk composition, or blood biochemical parameters, except for milk fat percentage. Simultaneously, milk fat percentage and milk fat yield increased linearly as the quantity of HMSeBA supplementation was increased. Production of 4% FCM and ECM was elevated linearly as dietary HMSeBA increased. The SO-0.3 group showed higher serum activity of glutathione peroxidase, total antioxidant capacity, and superoxide dismutase than the SS-0.3 group, but malondialdehyde content was not affected by Se source. Furthermore, HMSeBA supplementation linearly increased the activities of serum glutathione peroxidase and superoxide dismutase, but decreased malondialdehyde content. Compared with the SS-0.3 group, the SO-0.3 group showed augmented concentrations of total Se in milk and plasma, and total Se milk-to-plasma concentration ratio. In addition, increasing doses of HMSeBA linearly increased the concentrations of total Se in the milk and plasma. This study demonstrates that HMSeBA improves antioxidant status and increases milk and plasma Se concentrations more effectively than SS, indicating that HMSeBA could replace SS as an effective organic Se source for lactating dairy cows., (Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

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.)

According to the Nutritional Prevention of Cancer (NPC) trial, a selenized yeast supplement containing selenium, 200 mcg/day, decreased the incidence of total cancer, cancers of the prostate, colon and lung, and cancer mortality. The active agent in the selenized yeast supplement was assumed to be selenomethionine (SEMET), although the supplement had not been well speciated. The SELECT study, largely motivated by the NPC trial, enrolling nearly 40 times as many subjects, showed unequivocally that selenium 200 mcg/day, with selenium in the form of SEMET, does not protect selenium-replete men against prostate or other major cancer. The agent tested by SELECT, pure SEMET, could have been different from the selenized yeast tested in NPC. One of the selenium forms suspected of having chemopreventive effects, and which may have been present in the NPC agent, is methyl selenocysteine (MSC). This study, with 29 selenium-replete patients enrolled in a randomized, double-blind trial, compared the multiple-dose toxicity, pharmacokinetics and pharmacodynamics of MSC and SEMET. Patients were on trial for 84 days. No toxicity was observed. Although SEMET supplementation increased blood selenium concentration more than MSC did, neither form had a more than minimal impact on the two major selenoproteins: selenoprotein P(SEPP1) and glutathione peroxidase(GPX).

Aim: To evaluate molecular mechanisms of tissue-protective effects of antioxidants selenomethionine (SeMet) and D-pantethine (D-Pt) applied in combination with doxorubicin (Dx) in B16 melanoma-bearing-mice., Methods: Impact of the chemotherapy scheme on a survival of tumor-bearing animals, general nephro- and hepatotoxicity, blood cell profile in vivo, and ROS content in B16 melanoma cells in vitro was compared with the action of Dx applied alone. Nephrotoxicity of the drugs was evaluated by measuring creatinine indicator assay, hepatotoxicity was studied by measuring the activity of ALT/AST enzymes, and myelotoxicity was assessed by light microscopic analysis of blood smears. Changes in ROS content in B16 melanoma cells under Dx, SeMet, and D-Pt action in vitro were measured by incubation with fluorescent dyes dihydrodichlorofluoresceindiacetate (DCFDA, H2O2-specific) and dihydroethidium (DHE, O2--specific), and further analysis at FL1 (DCFDA) or FL2 channels (DHE) of FACScan flow cytometer. The impact of aforementioned compounds on functional status of mitochondria was measured by Rhodamine 123 assay and further analysis at FL1 channel of FACScan flow cytometer., Results: Selenomethionine (1200 µg/kg) and D-pantethine (500 mg/kg) in combination with Dx (10 mg/kg) significantly reduced tumor-induced neutrophilia, lymphocytopenia, and leukocytosis in comparison to Dx treatment alone. Moreover, SeMet and D-Pt decreased several side effects of Dx, namely an elevated creatinine level in blood and monocytosis, thus normalizing health conditions of B16 melanoma-bearing animals., Conclusions: Our results showed that antioxidants selenomethionine and D-pantethine possess significant nephroprotective and myeloprotective activity toward Dx action on murine B16 melanoma in vivo, but fail to boost a survival of B16 melanoma-bearing animals. The observed cytoprotective effects of studied antioxidants are not directly connected with their ROS scavenging.

Selenium and vitamin E micronutrients have been advocated for the prevention of colorectal cancer. Colorectal adenoma occurrence was used as a surrogate for colorectal cancer in an ancillary study to the Selenium and Vitamin E Cancer Prevention Trial (SELECT) for prostate cancer prevention. The primary objective was to measure the effect of selenium (as selenomethionine) on colorectal adenomas occurrence, with the effect of vitamin E (as α-tocopherol) supplementation on colorectal adenoma occurrence considered as a secondary objective. Participants who underwent lower endoscopy while in SELECT were identified from a subgroup of the 35,533 men randomized in the trial. Adenoma occurrence was ascertained from the endoscopy and pathology reports for these procedures. Relative Risk (RR) estimates and 95% confidence intervals (CI) of adenoma occurrence were generated comparing those randomized to selenium versus placebo and to vitamin E versus placebo based on the full factorial design. Evaluable endoscopy information was obtained for 6,546 participants, of whom 2,286 had 1+ adenomas. Apart from 21 flexible sigmoidoscopies, all the procedures yielding adenomas were colonoscopies. Adenomas occurred in 34.2% and 35.7%, respectively, of participants whose intervention included or did not include selenium. Compared with placebo, the RR for adenoma occurrence in participants randomized to selenium was 0.96 (95% CI, 0.90-1.02; P = 0.194). Vitamin E did not affect adenoma occurrence compared with placebo (RR = 1.03; 95% CI, 0.96-1.10; P = 0.38). Neither selenium nor vitamin E supplementation can be recommended for colorectal adenoma prevention. Cancer Prev Res; 10(1); 45-54. ©2016 AACR., (©2016 American Association for Cancer Research.)

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.)

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.

In previous studies we demonstrated that exposure to selenomethionine (SeMet) causes developmental toxicities in zebrafish (Danio rerio). The objectives of this study were to establish a dose-response relationship for developmental toxicities in zebrafish after embryo microinjection of Se (8, 16 or 32 μg/g dry mass of eggs) in the form of SeMet, and to investigate potential underlying mechanism(s) of SeMet-induced developmental toxicities. A dose-dependent increase in frequencies of mortality and total deformities, and reduced hatchability were observed in zebrafish exposed to excess Se via embryo microinjection. The egg Se concentration causing 20% mortality was then used to investigate transcript abundance of proteins involved in antioxidant protection and methylation. Excess Se exposure modified gene expression of oxidant-responsive transcription factors (nuclear factor erythroid 2-related factor nrf2a and nrf2b), and enzymes involved in cellular methylation (methionine adenosyltransferase mat1a and mat2ab) in zebrafish larvae. Notably, excess Se exposure up-regulated transcript abundance of aryl hydrocarbon receptor 2 (ahr2), a signalling pathway involved in the toxicity of dioxin-related compounds. Our findings suggest that oxidative stress or modification of methylation, or a combination of these mechanisms, might be responsible for Se-induced developmental toxicities in fishes.

Aim: To investigate the potential tissue-protective effects of antioxidants selenomethionine and D-pantethine applied together with doxorubicin (Dx) on NK/Ly lymphoma-bearing mice. The impact of this chemotherapy scheme on animal survival, blood cell profile, hepatotoxicity, glutathione level, and activity of glutathione-converting enzymes in the liver was compared with the action of Dx applied alone.., Methods: The hematological profile of animals was studied by the analysis of blood smears under light microscopy. Hepatotoxicity of studied drugs was evaluated measuring the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzymes, De Ritis ratio, and coenzyme A fractions by McDougal assay. Glutathione level in animal tissues was measured with Ellman reagent, and the activity of glutathione reductase, transferase, and peroxidase was measured using standard biochemical assays., Results: D-pantethine (500 mg/kg) and, to a lower extent, selenomethionine (600 µg/kg) partially reduced the negative side effects (leukocytopenia and erythropenia) of Dx (5 mg/kg) in NK/Ly lymphoma bearing animals on the 14th day of their treatment. This increased animal survival time from 47-48 to 60+ days and improved the quality of their life. This ability of D-pantethine and selenomethionine was realized via hepatoprotective and immunomodulating activities. D-pantethine also restored the levels of acid-soluble and free CoA in the liver of tumor-bearing animals, while selenomethionine caused the recovery of glutathione peroxidase levels in the liver, which was significantly diminished under Dx treatment. Both compounds decreased glutathione level in the liver, which was considerably induced by Dx., Conclusions: Antioxidants selenomethionine and D-pantethine partially reversed the negative side effects of Dx in NK/Ly lymphoma-bearing mice and significantly increased the therapeutic efficiency of this drug in tumor treatment.

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.)

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.)

Selenium (Se) is known to cause chronic toxicity in aquatic species. In particular, dietary exposure of fish to selenomethionine (SeMet), the primary form of Se in the diet, is of concern. Recent studies suggest that chronic exposure to elevated dietary SeMet alters energy and endocrine homeostasis in adult fish. However, little is known about the direct effects of dietary SeMet exposure in juvenile fish. The objective of the present study was to investigate sublethal physiological effects of dietary SeMet exposure in juvenile fathead minnow (Pimephales promelas). Twenty days-post-hatch fathead minnow were exposed for 60 days to different measured concentrations (2.8, 5.4, 9.9, 26.5 μg Se/g dry mass [dm]) of Se in food in the form of SeMet. After exposure, samples were collected for Se analysis and fish were subjected to a swimming performance challenge to assess critical swim speed (Ucrit), tail beat frequency and tail beat amplitude, oxygen consumption (MO2), cost of transport (COT), standard metabolic rate (SMR), active metabolic rate (AMR), and factorial aerobic scope (F-AS). Ucrit was decreased in the 26.5 μg Se/g dm exposure group compared to the control group. Tail beat frequency and tail beat amplitude were significantly reduced in fish fed 9.9 and 26.5 μg Se/g. An increase in MO2 and COT was observed in the 9.9 and 26.5 μg Se/g exposure groups compared to the control group. While the AMR of the high dose group was increased relative to control, there were no significant differences in SMR and F-AS. Energy storage capacity was measured via whole body triglyceride and glycogen concentrations. Triglyceride concentrations in non-swam fish were elevated in the 5.4 μg Se/g group relative to controls. Fatigued (swam) fish had significantly lower whole body triglycerides than non-swam fish. All non-swam SeMet exposure groups had significantly decreased whole body glycogen concentrations compared to controls, while the 5.4 and 26.5 μg Se/g exposure groups had significantly greater whole body glycogen concentrations in swam versus non-swam fish. A decrease in whole body cortisol was observed in swam fish in the 5.4 μg Se/g exposure group compared to control fish. Whole body cortisol was greater in control, 9.9 and 26.5 μg Se/g swam fish compared to non-swam fish. These results suggest that exposure to environmentally relevant concentrations of dietary SeMet impairs swimming performance, aerobic capacity, and energy homeostasis, potentially impacting survivability of juvenile fish in Se impacted aquatic ecosystems., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Selenium may play a beneficial role in multi-factorial illnesses with genetic and environmental linkages via epigenetic regulation in part via glutathione peroxidase (GPx) activity. A meta-analysis was undertaken to quantify the effects of dietary selenium supplementation on the activity of overall GPx activity in different tissues and animal species and to compare the effectiveness of different forms of dietary selenium. GPx activity response was affected by both the dose and form of selenium (p < 0.001). There were differences between tissues on the effects of selenium supplementation on GPx activity (p < 0.001); however, there was no evidence in the data of differences between animal species (p = 0.95). The interactions between dose and tissue, animal species and form were significant (p < 0.001). Tissues particularly sensitive to changes in selenium supply include red blood cells, kidney and muscle. The meta-analysis identified that for animal species selenium-enriched foods were more effective than selenomethionine at increasing GPx activity.

Epidemiologic and laboratory studies indicate that dietary selenium protects against prostate cancer. Results from clinical trials suggest that selenium-enriched yeast (SY) but not selenomethionine (SeMet) may be effective at reducing prostate cancer risk. Our objectives were to directly compare for the first time the effects of SeMet and SY on prostate cancer relevant biomarkers in men. We performed a randomized double blind, placebo-controlled trial of SY (200 or 285 μg/day) and SeMet (200 μg/day) administered for 9 months in 69 healthy men. Primary endpoints included blood levels of selenium-containing compounds and oxidative stress biomarkers [urine 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-iso-prostaglandin-F2α (8-iso-PGF2α) and blood glutathione (GSH)]. Secondary endpoints included plasma glucose and PSA levels. Compliance was high in all groups (>95%). Plasma selenium levels were increased 93%, 54%, and 86% after 9 months in SeMet and low- and high-dose SY groups, respectively, and returned to baseline levels after a 3-month washout (P < 0.05). Levels of 8-OHdG and 8-iso-PGF2α were decreased 34% and 28%, respectively, after 9 months in the high-dose SY group (P < 0.05). These decreases were greatest in individuals with low baseline plasma levels of selenium (<127 ng/mL). No changes in serum PSA or blood glucose and GSH were observed. Overall, we showed for the first time, reductions in biomarkers of oxidative stress following supplementation with SY but not SeMet in healthy men. These findings suggest that selenium-containing compounds other than SeMet may account for the decrease in oxidative stress., (©2014 American Association for Cancer Research.)

Chemopreventive effects of the essential trace element selenium against prostate cancer have been shown in preclinical models and human observational studies, but results from clinical trials have been disappointing. It appears that there is a threshold selenium (Se) status below which improvement will decrease prostate cancer risk, but above which supplemental Se may be deleterious. Different forms of selenium have different effects, and genetic and other factors modify selenium's chemopreventive potential. Identification of men most likely to benefit from Se status improvement could have significant public health benefits., (©2014 American Association for Cancer Research.)

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.

Despite some controversy, selenomethionine (SeMet)-mediated protection against colorectal cancer (CRC) might be a very promising non-cytotoxic option. However, responsive molecular targets and underlying mechanisms of SeMet-mediated chemoprevention are still unclear. Our aim was to discover new targets of SeMet-mediated chemoprevention in CRC using proteomics analysis. We found dietary SeMet supplementation before carcinoma initiation effectively suppressed polyp incidence and dysplastic lesions without any adverse effects. To determine chemopreventive targets of SeMet, we employed two-dimensional gel electrophoresis-based proteomics analysis in CRC mouse model. Pretreatment with SeMet apparently modulated the expression of 30 proteins with functions in major processes like chronic inflammation, oxidative stress and apoptosis as discovered through pathway analysis with Pathway Studio software. We validated four proteins selected from pathway analysis including prohibitin, purine nucleoside phosphorylase, annexin 2 and c-reactive protein by immunohistochemistry. 8-Hydroxy-2'-deoxyguanosine (8-OHdG), a known oxidative stress marker, was decreased by SeMet treatment in CRC mice as seen by immunohistochemistry. Further network analysis was done among these new four validated proteins, 8-OHdG and colorectal cancer. These four proteins found by proteomics analysis might be considered as potential chemopreventive biomarkers of SeMet against colon cancer and can help develop and improve approaches in preventive, therapeutic and prognostic aspects.

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.

Prostate cancer is the product of dysregulated homeostasis within the aging prostate. Supplementation with selenium in the form of selenized yeast (Se-yeast) significantly reduced prostate cancer incidence in the Nutritional Prevention of Cancer Trial. Conversely, the Selenium and Vitamin E Cancer Prevention Trial (SELECT) showed no such cancer-protective advantage using selenomethionine (SeMet). The possibility that SeMet and Se-yeast are not equipotent in promoting homeostasis and cancer risk reduction in the aging prostate has not been adequately investigated; no direct comparison has ever been reported in man or animals. Here, we analyzed data on prostatic responses to SeMet or Se-yeast from a controlled feeding trial of 49 elderly beagle dogs-the only non-human species to frequently develop prostate cancer during aging-randomized to one of five groups: control; low-dose SeMet, low-dose Se-yeast (3 μg/kg); high-dose SeMet, high-dose Se-yeast (6 μg/kg). After seven months of supplementation, we found no significant selenium form-dependent differences in toenail or intraprostatic selenium concentration. Next, we determined whether SeMet or Se-yeast acts with different potency on six markers of prostatic homeostasis that likely contribute to prostate cancer risk reduction-intraprostatic dihydrotestosterone (DHT), testosterone (T), DHT:T, and epithelial cell DNA damage, proliferation, and apoptosis. By analyzing dogs supplemented with SeMet or Se-yeast that achieved equivalent intraprostatic selenium concentration after supplementation, we showed no significant differences in potency of either selenium form on any of the six parameters over three different ranges of target tissue selenium concentration. Our findings, which represent the first direct comparison of SeMet and Se-yeast on a suite of readouts in the aging prostate that reflect flux through multiple gene networks, do not further support the notion that the null results of SELECT are attributable to differences in prostatic consequences achievable through daily supplementation with SeMet, rather than Se-yeast.

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.

To evaluate the potential efficacy of selenium and vitamin E as inhibitors of prostate carcinogenesis, four chemoprevention studies using a common protocol were done in a rat model of androgen-dependent prostate cancer. After stimulation of prostate epithelial cell proliferation by a sequential regimen of cyproterone acetate followed by testosterone propionate, male Wistar-Unilever rats received a single i.v. injection of N-methyl-N-nitrosourea (MNU) followed by chronic androgen stimulation via subcutaneous implantation of testosterone pellets. At 1 week post-MNU, groups of carcinogen-treated rats (39-44/group) were fed either a basal diet or a basal diet supplemented with l-selenomethionine (3 or 1.5 mg/kg diet; study 1), dl-alpha-tocopherol (vitamin E, 4,000 or 2,000 mg/kg diet; study 2), l-selenomethionine + vitamin E (3 + 2,000 mg/kg diet or 3 + 500 mg/kg diet; study 3), or selenized yeast (target selenium levels of 9 or 3 mg/kg diet; study 4). Each chemoprevention study was terminated at 13 months post-MNU, and prostate cancer incidence was determined by histopathologic evaluation. No statistically significant reductions in prostate cancer incidence were identified in any group receiving dietary supplementation with selenium and/or vitamin E. These data do not support the hypotheses that selenium and vitamin E are potent cancer chemopreventive agents in the prostate, and when considered with the recent clinical data reported in the Selenium and Vitamin E Cancer Prevention Trial (SELECT), show the predictive nature of this animal model for human prostate cancer chemoprevention.

Previous epidemiologic observational and experimental studies investigated the potential of antioxidant micronutrients to modulate cancer risk, but these studies produced inconsistent results. In this pilot, randomized, double-blind, placebo-controlled clinical trial (n = 47), we assessed the effects of an antioxidant micronutrient combination (800 mg dl-alpha-tocopherol acetate, 24 mg beta-carotene, 1.0 g vitamin C, 200 microg l-selenomethionine, 7.2 mg riboflavin, 80 mg niacin, 60 mg zinc, 5 mg manganese) given daily over 4 months on oxidative and inflammatory biomarkers in patients with a history of sporadic colorectal adenoma. Plasma tumor necrosis factor-alpha (TNF-alpha), interleukin-6, and F2-isoprostane concentrations were measured using ELISAs, and cystine (CySS) was measured using high-performance liquid chromatography. Plasma TNF-alpha concentration decreased in the active treatment group by 37% relative to the placebo group (P = 0.002), and CySS decreased by 19% (P = 0.03); however, interleukin-6 and F2-isoprostane concentrations decreased in antioxidant-treated nonsmokers but increased in smokers, although these findings were not statistically significant. The decreases of TNF-alpha and CySS were more pronounced in nonsmokers. These data suggest that (a) an antioxidant micronutrient cocktail can modulate biomarkers of oxidative stress and inflammation in humans and (b) the effects of antioxidant micronutrient supplementation on biomarkers of inflammation and oxidative stress may differ according to smoking status.

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.

This study examined the localization of cellular glutathione peroxidase (GPx1) and extracellular glutathione peroxidase (GPx3) in lactating mammary tissue and in primary cultures of bovine mammary epithelial cells (BMEC). The effect of selenium as selenomethionine (SeMet) on the growth and viability of BMEC and GPx protein expression and activity were also studied. Single mammary epithelial cells were recovered by serial collagenase/hyaluronidase digestion from lactating bovine mammary tissue and cultured in a low-serum collagen gel system enriched with lactogenic hormones and 0, 10, 20, or 50 nM SeMet. Positive immunostaining with anti-cytokeratin and bovine anti-casein confirmed the epithelial nature and differentiated state of BMEC. Addition of SeMet to media facilitated rapid confluence of BMEC and formation of dome structures. Immunohistochemical and immunocytochemical staining revealed that both GPx1 and GPx3 are synthesized by BMEC and localized in the cytoplasm and nucleus. Up to 50 nM SeMet linearly increased BMEC number and viability over 5 d of culture. Bovine mammary epithelial cells cultured in SeMet-supplemented medium also exhibited markedly elevated GPx activity and linear increases in abundance of GPx1 and GPx3 proteins. It is apparent that SeMet degradation to release Se for synthesis of selenoproteins is carried out by BMEC. Results indicate that bovine mammary epithelial cells express GPx1 and GPx3 in vivo and in vitro; SeMet enhances expression of these selenoproteins in vitro and the growth and viability of BMEC.

Background: Secondary analyses of two randomized, controlled phase III trials demonstrated that selenium and vitamin E could reduce prostate cancer incidence. To characterize pharmacodynamic and gene expression effects associated with use of selenium and vitamin E, we undertook a randomized, placebo-controlled phase IIA study of prostate cancer patients before prostatectomy and created a preoperative model for prostatectomy tissue interrogation., Methods: Thirty-nine men with prostate cancer were randomly assigned to treatment with 200 microg of selenium, 400 IU of vitamin E, both, or placebo. Laser capture microdissection of prostatectomy biopsy specimens was used to isolate normal, stromal, and tumor cells. Gene expression in each cell type was studied with microarray analysis and validated with a real-time polymerase chain reaction (PCR) and immunohistochemistry. An analysis of variance model was fit to identify genes differentially expressed between treatments and cell types. A beta-uniform mixture model was used to analyze differential expression of genes and to assess the false discovery rate. All statistical tests were two-sided., Results: The highest numbers of differentially expressed genes by treatment were 1329 (63%) of 2109 genes in normal epithelial cells after selenium treatment, 1354 (66%) of 2051 genes in stromal cells after vitamin E treatment, and 329 (56%) of 587 genes in tumor cells after combination treatment (false discovery rate = 2%). Validation of 21 representative genes across all treatments and all cell types yielded Spearman correlation coefficients between the microarray analysis and the PCR validation ranging from 0.64 (95% confidence interval [CI] = 0.31 to 0.79) for the vitamin E group to 0.87 (95% CI = 0.53 to 0.99) for the selenium group. The increase in the mean percentage of p53-positive tumor cells in the selenium-treated group (26.3%), compared with that in the placebo-treated group (5%), showed borderline statistical significance (difference = 21.3%; 95% CI = 0.7 to 41.8; P = .051)., Conclusions: We have demonstrated the feasibility and efficiency of the preoperative model and its power as a hypothesis-generating engine. We have also identified cell type- and zone-specific tissue effects of interventions with selenium and vitamin E that may have clinical implications.