Biomarkers Of Selenium Status Research Articles

Toenail selenium, plasma selenoprotein P and risk of advanced prostate cancer: A nested case-control study.

Low selenium status may be associated with increased risk of prostate cancer (PC), particularly aggressive PC, and variation in selenoprotein genes may constitute an important modifying factor. We aimed to investigate the association between two selenium status biomarkers [toenail selenium, plasma selenoprotein P (SELENOP)] and risk of advanced, high-grade and advanced-stage PC. We further studied whether variations in selenoprotein genes were associated with PC risk and selenium biomarker concentrations. In the "Diet, Cancer and Health" cohort, 27 178 men aged 50 to 65 years were enrolled from 1993 to 1997. Between baseline and 2012, 1160 cohort participants were diagnosed with advanced PC; among these 462 had high-grade and 281 had advanced-stage disease at diagnosis. Each case was risk set-matched to one control. Toenail selenium and plasma SELENOP concentrations were measured by neutron activation analysis and a SELENOP-ELISA, respectively, and genotyping was performed for 27 selected single nucleotide polymorphisms (SNPs) in 12 selenium pathway genes (including seven selenoproteins) by allele-specific PCR. Toenail selenium and circulating SELENOP concentrations were not associated with advanced, high-grade or advanced-stage PC. After adjustment for multiple testing, none of the genes were associated with PC risk. Neither toenail selenium nor plasma SELENOP was associated with advanced, high-grade or advanced-stage PC.

High dietary inorganic selenium has minimal effects on turkeys and selenium status biomarkers.

The current NRC turkey Se requirement is 0.2μg Se/g diet. Recent studies evaluating tissue Se, glutathione peroxidase (GPX) activities, and selenoprotein transcript expression concluded that the dietary Se requirement of the turkey poult should be raised to 0.4μg Se/g when supplemented with inorganic Se. The FDA currently limits Se inclusion in premixed diets for poultry and other livestock species to 0.3μg Se/g diet. Thus, there is a need to investigate the effect of high dietary Se (>1.0μg Se/g) in turkeys. The present study fed turkey poults 2 and 5μg Se/g diet to characterize tissue Se accumulation in turkey poults fed high dietary inorganic Se and to evaluate the efficacy of selenoprotein activity and transcript expression as biomarkers of high Se status. Day-old male poults were fed 0.4, 2, or 5μg Se/g for 28 d. There was no significant effect of Se supplementation on poult growth. Supplementation with 5μg Se/g diet resulted in Se concentrations that were 5.6X, 1.7X, 1.9X, and 2.0X greater than Se-adequate levels in liver, kidney, breast, and thigh, respectively, and GPX activities in plasma, red cells, liver, kidney, and heart that were ≤2.0X Se-adequate values. In liver, kidney, heart, gizzard, breast, or thigh, no selenoprotein transcript was increased ≥2.0X, and no selenoprotein transcript was decreased ≤0.5X by 2 or 5μg Se/g diet as compared to poults fed 0.4μg Se/g diet. Of the 112 Se status biomarkers reported in this study, liver Se concentration was the only biomarker markedly altered by high Se status. This study provides evidence of no adverse effects in turkey poults fed up to 5μg Se/g diet as inorganic Se. Thus, the FDA limit for Se supplementation in turkey feed can be safely raised to 0.5μg Se/g diet. Future studies are needed to identify biomarkers for high Se status and to better understand how turkeys maintain Se homeostasis and resist Se toxicity.

Influence of Gender and SNPs in GPX1 Gene on Biomarkers of Selenium Status in Healthy Brazilians.

Selenium (Se) status varies worldwide as a result of natural variation of Se content in soils, dietary pattern, and the presence of SNPs. Further, Se status in Brazilians and its relationship between genetic variation and Se biomarkers is unknown. This work investigated the association between SNPs in glutathione peroxidase genes and biomarkers of Se status in healthy Brazilians. The study was conducted in 116 healthy adults in São Paulo, Brazil. Plasma and erythrocyte Se were measured by HGFAAS. Erythrocyte GPx (eGPx) activity was measured spectrometrically in a biochemical analyzer. Genotypes were determined by real-time PCR using Taqman® Assays. eGPx activity was higher in females compared with males. Lower erythrocyte Se concentrations were found in heterozygous GC carriers for GPX1 rs8179169. eGPx activity was higher in females with the common genotypes, except for rs8179169. GC carriers for rs8179169 had lower erythrocyte Se in both genders, and only male carriers of the variant alleles of both rs1050450 and rs1800668 had higher eGPx activity. In conclusion, the genotype for SNPs in GPX1 and gender affected biomarkers of Se status in this pilot study with healthy Brazilians.

Biomarkers of selenium status in dogs.

BackgroundInadequate dietary selenium (Se) intake in humans and animals can lead to long term health problems, such as cancer. In view of the owner’s desire for healthy longevity of companion animals, the impact of dietary Se provision on long term health effects warrants investigation. Little is currently known regards biomarkers, and rate of change of such biomarkers in relation to dietary selenium intake in dogs. In this study, selected biomarkers were assessed for their suitability to detect changes in dietary Se in adult dogs within eight weeks.ResultsTwenty-four dogs were fed a semi-purified diet with an adequate amount of Se (46.1 μg/MJ) over an 8 week period. They were then divided into two groups. The first group remained on the adequate Se diet, the second were offered a semi-purified diet with a low Se concentration (6.5 μg/MJ; 31 % of the FEDIAF minimum) for 8 weeks. Weekly urine and blood was collected and hair growth measurements were performed. The urinary Se to creatinine ratio and serum Se concentration were significantly lower in dogs consuming the low Se diet from week 1 onwards, by 84 % (adequate 25.3, low 4.1) and 7 % (adequate 257 μg/L, low 238 μg/L) respectively. Serum and whole blood glutathione peroxidase were also significantly lower in dogs consuming the low Se diet from weeks 6 and 8 respectively. None of the other biomarkers (mRNA expression and serum copper, creatine kinase, triiodothyronine:thyroxine ratio and hair growth) responded significantly to the low Se diet over the 8 week period.ConclusionsThis study demonstrated that urinary Se to creatinine ratio, serum Se and serum and whole blood glutathione peroxidase can be used as biomarkers of selenium status in dogs. Urinary Se to creatinine ratio and serum Se concentrations responded faster to decreased dietary Se than the other parameters. This makes these biomarkers candidates for early screening of long term effects of dietary Se provision on canine health.

EURRECA—Estimating Selenium Requirements for Deriving Dietary Reference Values

Current reference values for selenium, an essential micronutrient, are based on the intake of selenium that is required to achieve maximal glutathione peroxidase activity in plasma or erythrocytes. In order to assess the evidence of relevance to setting dietary reference values for selenium, the EURRECA Network of Excellence focused on systematic searches, review, and evaluation of (i) selenium status biomarkers and evidence for relationships between intake and status biomarkers, (ii) selenium and health (including the effect of intake and/or status biomarkers on cancer risk, immune function, HIV, cognition, and fertility), (iii) bioavailability of selenium from the diet, and (iv) impact of genotype/single nucleotide polymorphisms on status or health outcomes associated with selenium. The main research outputs for selenium and future research priorities are discussed further in this review.

S-Adenosylmethionine-dependent Protein Methylation Is Required for Expression of Selenoprotein P and Gluconeogenic Enzymes in HepG2 Human Hepatocytes

Cellular methylation processes enable expression of gluconeogenic enzymes and metabolism of the nutrient selenium. Selenium status has been proposed to relate to type II diabetes risk, and plasma levels of selenoprotein P (SEPP1) have been positively correlated with insulin resistance. Increased expression of gluconeogenic enzymes glucose-6-phosphatase (G6PC) and phosphoenolpyruvate carboxykinase 1 (PCK1) has negative consequences for blood glucose management in type II diabetics. Transcriptional regulation of SEPP1 is directed by the same transcription factors that control the expression of G6PC and PCK1, and these factors are activated by methylation of arginine residues. We sought to determine whether expression of SEPP1 and the aforementioned glucoconeogenic enzymes are regulated by protein methylation, the levels of which are reliant upon adequate S-adenosylmethionine (SAM) and inhibited by S-adenosylhomocysteine (SAH). We treated a human hepatocyte cell line, HepG2, with inhibitors of adenosylhomocysteine hydrolase (AHCY) known to increase concentration of SAH before analysis of G6PC, PCK1, and SEPP1 expression. Increasing SAH decreased 1) the SAM/SAH ratio, 2) protein-arginine methylation, and 3) expression of SEPP1, G6PC, and PCK1 transcripts. Furthermore, hormone-dependent induction of gluconeogenic enzymes was reduced by inhibition of protein methylation. When protein-arginine methyltransferase 1 expression was reduced by siRNA treatment, G6PC expression was inhibited. These findings demonstrate that hepatocellular SAM-dependent protein methylation is required for both SEPP1 and gluconeogenic enzyme expression and that inhibition of protein arginine methylation might provide a route to therapeutic interventions in type II diabetes.

Selenium and cancer: biomarkers of selenium status and molecular action of selenium supplements

The relationship between selenium and cancer involves many different aspects. These include the forms of selenium present in the diet and in the body, their functions and mechanisms of action, and methods employed in assessing an individual's selenium nutritional status-both in general, and in epidemiological studies of the risk of cancer in relation to diet, as well as in connection with long-term trials for investigating the disease-preventive potential of selenium supplementation. To review different aspects on selenium metabolism, the occurrence of different selenoproteins and their use as biomarkers of selenium status, the results of intervention trials of the cancer-preventive effects of selenium supplementation, the mechanisms of action involved, together with epidemiological findings on relations between the selenium status in the body and risk of cancer. The rapid advance in the knowledge of different selenoproteins and their biological functions has opened up new possibilities for the understanding of the biological effects of selenium supplementation. A wide variety of effects of different forms and doses of selenium has been observed in a number of experimental systems, and it is at present difficult to pinpoint the mechanism that may explain the positive preventive effects of selenium supplementation observed in some human long-term trials. Moreover, additional such trials are needed to define the benefits and risks of different types and doses of selenium supplements which in the future may be implemented for public health reasons. Another necessary focus for future research is a better understanding of the mechanisms by which selenium interferes with the carcinogenesis process.

Biomarkers of selenium status in the amazonian context: Blood, urine and sequential hair segments

Selenium (Se) is an essential element and deficit or excess of dietary Se is associated with health disorders. Relatively elevated Se levels have been reported in the Brazilian Amazon, where there are also important annual variations in the availability of different foods. The present study was conducted among six riparian communities of the Tapajós River to evaluate seasonal variations in blood and sequential hair cm Se concentrations, and to examine the relationships between Se in blood and hair, and blood and urine. Two cross-sectional studies were conducted, at the descending water (DWS, n=259) and the rising water (RWS, n=137) seasons, with repeated measures for a subgroup (n=112). Blood Se (B-Se), hair Se (H-Se) and urine Se (U-Se) were determined. Match-paired analyses were used for seasonal comparisons and the method of best fit was used to describe the relationships between biomarkers. B-Se levels presented a very large range (142-2447 microg/l) with no overall seasonal variation (median 284 and 292 microg/l, respectively). Sequential analysis of 13 cm hair strands showed significant variations over time: Se concentrations at the DWS were significantly lower compared with the rising water season (medians: 0.7 and 0.9 microg/g; ranges: 0.2-4.3 microg/g and 0.2-5.4 microg/g, respectively). At both seasons, the relationships between B-Se and H-Se were linear and highly significant (r(2)=67.9 and 63.6, respectively), while the relationship between B-Se and U-Se was best described by a sigmoid curve. Gender, age, education and smoking did not influence Se status or biomarker relationships. Variations in H-Se suggest that there may be seasonal availability of Se sources in local food. For populations presenting a large range and/or elevated Se exposure, sequential analyses of H-Se may provide a good reflection of variations in Se status.

Renal function of chloralkali workers after the cessation of exposure to mercury vapor

The aims of the study were to assess renal function in chloralkali workers previously exposed to mercury vapor and to assess the impact of selenium status on the biomarkers of kidney function. Forty-nine chloralkali workers previously exposed to mercury vapor were compared with 49 age-matched referents in a cross-sectional study. Selected biomarkers of kidney function and biomarkers of selenium status were measured. The index group had been exposed for 13.1 (range 2.8-34.5) years on the average at a mean urinary mercury excretion of 9.3 (range 4.0-25.4) nmol/mmol creatinine a year. The exposure had ceased on an average of 4.8 (range 4.2-10.0) years prior to the examinations. No statistically significant differences were found between the groups for the measured biomarkers of kidney function. The serum selenium concentration and serum glutathione peroxidase activity were associated with the activity of N-acetyl-beta-D-glucosaminidase in urine (U-NAG). The results indicate that having higher glutathione peroxidase activity or a higher serum selenium concentration results in a lower excretion of U-NAG. This effect was the most pronounced in the oldest third of the participants. Apparently the well-known association between U-NAG and age could only be found for the participants with a lower selenium status. Increased activities of U-NAG during ongoing exposure to mercury vapor appear to be reversible upon cessation of exposure. Selenium status has a substantial impact on U-NAG activity and should be considered in studies of U-NAG excretion.

Glutathione Peroxidase, Selenoprotein P and Selenium in Serum of Elderly Subjects in Relation to Other Biomarkers of Nutritional Status and Food Intake

The relation of the intake of selenium and different food groups to serum levels of selenium, glutathione peroxidase and selenoprotein P, and urinary selenium was studied in 50- to 69-year-old subjects (101 men, 105 women). Blood was sampled six times during the course of 1 year, and during the same time the subjects performed six 3-day weighed dietary records. The concentration of glutathione peroxidase in serum was higher among men (4.3 (0.74) mg/L) (mean (SD)) than among women (4.0 (0.76) mg/L, P < 0.03), whereas men had lower serum selenium (1.10 (0.17) μmol/L) vs. 1.17 (0.19) μmol/L, P < 0.01). The intake of selenium among men was calculated to be 36 (18–54) μg/day and among women 29 (13–48) μg/day (geometric means (90% central range)), but there was no significant gender difference when the selenium intake was corrected for energy intake. No difference between men and women was observed for serum selenoprotein P (1.47 (0.25) a.u. versus 1.47 (0.24) a.u. (mean(SD)) or urinary selenium excretion (0.31 (0.09) μmol/d vs. 0.27 (0.08) μmol/d). Serum selenium was significantly associated with selenoprotein P in both sexes but with glutathione peroxidase only in men. Serum selenium had a marked association with urinary selenium excretion. Selenium intake was significantly associated with serum selenium in men, and with selenoprotein P and urinary selenium in women. Among 11 major food groups, the intakes of fish and milk products were significantly associated with biomarkers of selenium status among women. Calculation of the association between biomarkers of selenium status and variables on intake and serum content of nutrients using multiple regression analysis resulted in most cases in low explanatory power. The variables most consistently related to more than one variable of selenium status were serum levels of retinol, α-tocopherol and eicosapentaenoic acid, and intake of protein. The study shows that individual biomarkers of selenium status are associated differently to variables on dietary intake and nutritional status.