low-Se Diet Research Articles

The Effects of Low Selenium on DNA Methylation in the Tissues of Chickens.

DNA methylation is involved in epigenetic mechanisms associated with gene suppression, and its abnormalities lead to gene instability and disease development. As an essential trace element in humans and animals, selenium (Se) is also associated with abnormal changes in DNA methylation. However, the effect of low Se on DNA methylation in avian tissues has not been reported. In the current study, chickens were fed a low-Se diet (0.033mgSe/kg) or supplemented with 0.15mgSe/kg as selenite for up to 55days. DNA methylation levels were examined by high-performance liquid chromatography (HPLC). DNA methyltransferases (DNMTs) and methyl-DpG-binding domain protein 2 (MBD2) mRNA levels were examined through the applications of RT-PCR. The experiment aims to explore the relationship between low Se and DNA methylation. The results showed that total DNA methylation levels in the muscle tissues, brain, immune tissues, and liver of the low-selenium diet group were decreased compared with the control group. The degree of DNA methylation reduction in different tissues from largest to smallest was liver > cerebellum > thymus > brain > spleen ≥ leg muscles > pectoral muscles > bursa of Fabricius > thalamus > wing muscles. DNMT1, DNMT3A, and DNMT3B mRNA expression levels of the low-selenium diet group were decreased compared with those in the control group. The mRNA expression of the MBD2 gene was increased. The results indicate that low Se can reduce the DNA methylation levels of tissues, especially within the liver. These conclusions provide a basis for exploring the pathogenesis of selenium deficiency from the perspective of DNA methylation and create a new basis for comparative medicine.

Maternal selenium status is profoundly involved in metabolic fetal programming by modulating insulin resistance, oxidative balance and energy homeostasis.

High and low levels of selenium (Se) have been related to metabolic disorders in dams and in their offspring. Their relationship to oxidative balance and to AMP-activated protein kinase (AMPK) is some of the mechanisms proposed. The aim of this study is to acquire information about how Se is involved in metabolic programming. Three experimental groups of dam rats were used: control (Se: 0.1ppm), Se supplemented (Se: 0.5ppm) and Se deficient (Se: 0.01ppm). At the end of lactation, the pups' metabolic profile, oxidative balance, Se levels, selenoproteins and IRS-1 hepatic expression, as well as hepatic AMPK activation were measured. The experimental groups present deep changes in Se homeostasis, selenoproteins and IRS-1 hepatic expression, oxidative balance, AMPK activation ratio and insulin levels. They do, however, have different metabolic profiles. High- and low-Se diets are linked to insulin resistance, yet the mechanisms involved are completely opposite.

Pharmacokinetics of Sodium Selenite Administered Orally in Blood and Tissues of Selenium-Deficient Ducklings.

Selenium (Se) is an essential trace element for humans and animals. Appropriate amount of Se in the body can prevent a variety of diseases. However, Se deficiency leads to pathological changes such as skeletal muscle necrosis and pancreatic atrophy in livestock and poultry. Se preparations are widely used in the prevention and treatment of Se-deficient disease, but there is no unified standard of medication, and the safe dose range of Se is narrow. Therefore, it is of great significance to study the pharmacokinetics of low-Se ducklings and to formulate drug administration schemes. In the present study, eighty 1-day-old healthy ducklings were randomly selected, and fed with low-Se diet to 30days of age (blood Se content ≦0.03μg/mL). After the low Se duckling models were duplicated, blood samples and tissues of livers, pancreases, and thigh muscles were collected at different time points to detect Se content following oral administration of 0.1% sodium selenite (Na2SeO3) at 0.8mg/kgBW, and the pharmacokinetics parameters were automatically calculated by MCPKP program. The results showed that pharmacokinetics characteristics of Na2SeO3 in blood, livers, and pancreases of ducklings were consistent with the first-order absorption and two-compartment open models; in thigh muscles was consistent with the first-order absorption and one compartment with a lag time open model. The primary kinetic parameters of Na2SeO3 in blood: the half-life of absorption was 5.9026h, the time of reaching maximum concentration was 23.03h, and the half-life of elimination was 131.13h. The absorption of Na2SeO3 in livers was the quickest, pancreases and thigh muscles were in order of becoming slower, and the elimination of Na2SeO3 in thigh muscles was the quickest, livers and pancreases were in order of becoming slower. The administration parameters of multi-dose were calculated according to the kinetic of single-dose: loading dose (D*) was 1.7046mg/kgBW, maintenance dose (D0) was 0.8mg/kgBW, and dosing interval (τ) was 120h. The results of this study can supplement and improve the theoretical system of Se metabolic kinetics, and provide experimental basis for the prevention and treatment of Se deficiency disease by rational drug use.

Selenium-sensitive miRNA-181a-5p targeting SBP2 regulates selenoproteins expression in cartilage.

Selenium (Se) deficiency brings about defects in the biosynthesis of several selenoproteins and has been associated with aberrant chondrogenesis. Selenocysteine (Sec) Insertion Sequence (SECIS) and SECIS binding protein 2 (SBP2) interaction is a very critical node for the metabolic balance between Se and selenoproteins. The Gpx1, Gpx4 and SelS have different binding affinities with SBP2 in cells. According to our results, both miR‐181a‐5p and SBP2 appeared to be selenium‐sensitive and regulated the expression of selenoproteins in C28/I2 cells under Se sufficient environment. However, they showed significantly opposite expression trend in Se deficiency rats cartilage and SeD C28/I2 cells. The SBP2 is a direct target gene of miR‐181a‐5p in C28/I2 cells as determined by reporter gene and off‐target experiments. And the miR‐181a‐5p could regulate SBP2 and the selenoproteins in C28/I2 cells. Depending upon the Se supply levels, C28/I2 cells were divided into three groups, that is normal Se, SeD and SeS, which underwent through a 7‐day Se deprivation process, then SBP2 was knocked‐down and overexpressed in all the groups. Moreover, the selected selenoproteins were down‐regulated in second‐generation low Se diet rat cartilage. The selenoproteins expression was decreased by Se deficiency which depended on the Selenium‐sensitive miR‐181a‐5p to participate and regulate SBP2 at post‐transcriptional level. It involves a series of antioxidant and ECM (extracellular matrix) genes, to overcome the ROS‐related stress for the protection of essential physiological functions and to maintain the balance between anabolism and catabolism of the cartilage.

Endogenous Hydrogen Sulfide Promotes Apoptosis via Mitochondrial Pathways in the Livers of Broilers with Selenium Deficiency Exudative Diathesis Disease.

Hydrogen sulfide (H2S), an endogenous gasotransmitter, plays an important role in apoptosis. Exudative diathesis (ED) disease is associated with dietary selenium (Se) deficiency in broilers. The liver is one of the target organs of Se deficiency; however, little is known about the effect of H2S on apoptosis via mitochondrial pathways in the livers of broilers with ED disease. In the present study, we aimed to investigate the correlation between endogenous H2S and mitochondrial-mediated apoptosis in the livers of broilers with ED disease, as induced by Se deficiency. One hundred twenty healthy, 1-day-old broilers were randomly assigned to one of two groups (60 each) based on diet: Basal diet (control group, 0.2mg/kg Se) or a low-Se diet (-Se group, 0.033mg/kg Se). At day 20, 15 broilers of a similar weight were sacrificed from the control group, while the same number of broilers were euthanatized from the -Se group when displaying typical symptoms of ED between days 18 and 25. The livers were collected, and apoptosis was measured using a TUNEL assay. Additionally, H2S concentration, the expression of H2S synthases of cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MST), as well as mitochondrial apoptosis-related genes of Bcl-2, Bax, Bak, Cyt-C, Caspase-9, Caspase-3, and p53, were examined in livers. The results indicated that Se deficiency could induce apoptosis in the livers of broilers. Swelling, fractures, and vacuolization were visible in the mitochondrial cristae in the livers of the -Se group. The expression of H2S synthase-related genes and H2S concentration was significantly enhanced (P < 0.05) in the livers of the -Se group compared to controls. Moreover, a low-Se diet downregulated (P < 0.05) the level of Bcl-2 and upregulated (P < 0.05) the levels of Bax, Bak, Cyt-C, Caspase-9, Caspase-3, and p53. These results suggest that an H2S increase in the livers of ED broilers, which was induced by Se deficiency, is related to apoptosis mediated by mitochondrial pathways.

Sensitivity and toxic mode of action of dietary organic and inorganic selenium in Atlantic salmon (Salmo salar)

Depending on its chemical form, selenium (Se) is a trace element with a narrow range between requirement and toxicity for most vertebrates. Traditional endpoints of Se toxicity include reduced growth, feed intake, and oxidative stress, while more recent finding describe disturbance in fatty acid synthesis as underlying toxic mechanism. To investigate overall metabolic mode of toxic action, with emphasis on lipid metabolism, a wide scope metabolomics pathway profiling was performed on Atlantic salmon (Salmo salar) (572±7g) that were fed organic and inorganic Se fortified diets. Atlantic salmon were fed a low natural background organic Se diet (0.35mg Se kg−1, wet weight (WW)) fortified with inorganic sodium selenite or organic selenomethionine-yeast (SeMet-yeast) at two levels (∼1–2 or 15mgkg−1, WW), in triplicate for 3 months. Apparent adverse effects were assessed by growth, feed intake, oxidative stress as production of thiobarbituric acid-reactive substances (TBARS) and levels of tocopherols, as well as an overall metabolomic pathway assessment. Fish fed 15mgkg−1 selenite, but not 15mgkg−1 SeMet-yeast, showed reduced feed intake, reduced growth, increased liver TBARS and reduced liver tocopherol. Main metabolic pathways significantly affected by 15mgkg−1 selenite, and to a lesser extent 15mgkg−1 SeMet-yeast, were lipid catabolism, endocannabinoids synthesis, and oxidant/glutathione metabolism. Disturbance in lipid metabolism was reflected by depressed levels of free fatty acids, monoacylglycerols and diacylglycerols as well as endocannabinoids. Specific for selenite was the significant reduction of metabolites in the S-Adenosylmethionine (SAM) pathway, indicating a use of methyl donors that could be allied with excess Se excretion. Dietary Se levels to respectively 1.1 and 2.1mgkg−1 selenite and SeMet-yeast did not affect any of the above mentioned parameters. Apparent toxic mechanisms at higher Se levels (15mgkg−1) included oxidative stress and altered lipid metabolism for both inorganic and organic Se, with higher toxicity for inorganic Se.

Variable Effects of Dietary Selenium in Mice That Spontaneously Develop a Spectrum of Thyroid Autoantibodies.

Selenium (Se) is a critical element in thyroid function, and variable dietary Se intake influences immunity. Consequently, dietary Se could influence development of thyroid autoimmunity and provide an adjunct to treat autoimmune thyroid dysfunction. Nonobese diabetic (NOD).H2h4 mice spontaneously develop autoantibodies to thyroglobulin (Tg) and thyroid peroxidase (TPO). This mouse strain expressing a human thyroid-stimulating hormone receptor (TSHR) A-subunit transgene in the thyroid also develops pathogenic TSHR autoantibodies. In this report, we investigated whether dietary Se influences these immune processes. Male and female wild-type and transgenic NOD.H2h4 mice were maintained on normal-, low-, or high-Se (0.1, 0, or 1.0 mg/kg) rodent diets. After 4 months, Se serum levels were extremely low or significantly increased on 0 or 1.0 mg/kg Se, respectively. Varying Se intake affected Tg antibody (TgAb) levels after 2 (but not 4) months; conversely, TPO antibody (TPOAb) levels were altered by dietary Se after 4 (but not 2) months. These data correspond to the earlier development of TgAb than TPOAb in NOD.H2h4 mice. In males, TgAb levels were enhanced by high Se and in females by low Se intake. Se intake had no effect on pathogenic TSHR autoantibodies in TSHR transgenic NOD.H2h4 females. In conclusion, in susceptible NOD.H2h4 mice, we found no evidence that a higher dietary Se intake ameliorates thyroid autoimmunity by reducing autoantibodies to Tg, TPO, or the TSHR. Instead, our finding that low dietary Se potentiates the development of autoantibodies to Tg and TPO in females is consistent with reports in humans of an increased prevalence of autoimmune thyroiditis in low-Se regions.

Reduced Dietary Selenium Impairs Vascular Function by Increasing Oxidative Stress in Sprague-Dawley Rat Aortas.

This study aimed to determine whether low dietary Se content affects the function and mechanisms mediating the vascular relaxation of rat aortas, and to test the role of oxidative stress in observed differences. Male Sprague Dawley (SD) rats were maintained for 10 weeks on low Se (low-Se group; N = 20) or normal Se content (norm-Se group; N = 20) rat chow. Dose responses to acetylcholine (ACh; 10−9–10−5M) and the response to reduced pO2 were tested in noradrenaline-precontracted aortic rings in the absence/presence of the nitric oxide synthase (NOS) inhibitor nitro-l-arginine methyl ester (l-NAME), the cyclooxygenase 1 and 2 (COX-1, 2) inhibitor Indomethacin, and the antioxidative agent Tempol in tissue bath. mRNA expression of glutathione peroxidase 1 (GPx1), catalase (CAT), and Cu/Zn superoxide dismutase (SOD) was measured in rat aortas. Oxidative stress (Thiobarbituric Acid Reactive Substances; TBARS), antioxidative plasma capacity (ferric reducing ability of plasma assay; FRAP), and protein levels of GPx1 were measured in plasma and serum samples, respectively. Reduced ACh-induced relaxation (AChIR) (dominantly mediated by NO) in the low-Se group compared to the norm-Se group was restored by Tempol administration. Hypoxia-induced relaxation (HIR) (dominantly mediated by COX-1, 2), TBARS, and FRAP as well as GPx1 serum concentrations were similar between the groups. mRNA GPx1 expression in rat aortas was significantly decreased in the low-Se compared to the norm-Se group. These data suggest that low dietary Se content increases the local oxidative stress level, which subsequently affects the NO-mediated vascular response.

Selenium deficiency risk predicted to increase under future climate change

Deficiencies of micronutrients, including essential trace elements, affect up to 3 billion people worldwide. The dietary availability of trace elements is determined largely by their soil concentrations. Until now, the mechanisms governing soil concentrations have been evaluated in small-scale studies, which identify soil physicochemical properties as governing variables. However, global concentrations of trace elements and the factors controlling their distributions are virtually unknown. We used 33,241 soil data points to model recent (1980-1999) global distributions of Selenium (Se), an essential trace element that is required for humans. Worldwide, up to one in seven people have been estimated to have low dietary Se intake. Contrary to small-scale studies, soil Se concentrations were dominated by climate-soil interactions. Using moderate climate-change scenarios for 2080-2099, we predicted that changes in climate and soil organic carbon content will lead to overall decreased soil Se concentrations, particularly in agricultural areas; these decreases could increase the prevalence of Se deficiency. The importance of climate-soil interactions to Se distributions suggests that other trace elements with similar retention mechanisms will be similarly affected by climate change.

Oxidative stress induced by Se-deficient high-energy diet implicates neutrophil dysfunction via Nrf2 pathway suppression in swine.

The mechanism of the interaction between Se deficiency and high energy remains limited. The aim of the current study was to identify whether Se-deficient, high-energy diet can induce oxidative stress, and downregulate the Nrf2 pathway and phagocytic dysfunction of neutrophils. We detected the phagocytic activity, ROS production, protein levels of Nrf2 and Nrf2 downstream target genes, and the mRNA levels of 25 selenoproteins, heat shock proteins, and cytokines in neutrophils. Cytokine ELISA kits were used to measure the serum cytokines. The concentration of ROS was elevated (P < 0.05) in obese swine fed on a low Se diet (less than 0.03 mg/kg Se) compared to control swine. The protein levels of Nrf2 and its downstream target genes were depressed during Se deficiency and high-energy intake. The mRNA levels of 16 selenoproteins were significantly decreased (P < 0.05) in the Se-deficient group and Se-deficient, high-energy group compared to the control group. However, the mRNA levels of 13 selenoproteins in peripheral blood neutrophils were upregulated in high energy group, except TrxR1, SelI and SepW. In summary, these data indicated that a Se-deficient, high-energy diet inhibits the Nrf2 pathway and its regulation of oxidative stress, and prompted a pleiotropic mechanism that suppresses phagocytosis.

Delineating hierarchy of selenotranscriptome expression and their response to selenium status in chicken central nervous system

Selenium (Se) incorporated in selenoproteins as selenocysteine and supports various important cellular and organismal functions. We recently reported that chicken brain exhibited high priority for Se supply and retention under conditions of dietary Se deficiency and supernutrition Li et al. (2012) . However, the selenotranscriptome expressions and their response to Se status in chicken central nervous system (CNS) are unclear. To better understand the relationship of Se homeostasis and selenoproteins expression in chicken CNS, 1day-old HyLine White chickens were fed a low Se diet (Se-L, 0.028mg/g) supplemented with 4 levels of dietary Se (0 to 5.0mgSe/kg) as Na2SeO3 for 8weeks. Then chickens were dissected for getting the CNS, which included cerebral cortex, cerebellum, thalamus, bulbus cinereus and marrow. The expressions of selenoproteome which have 24 selenoproteins were detected by the quantitative real-time PCR array. The concept of a selenoprotein hierarchy was developed and the hierarchy of different regions in chicken CNS was existence, especially cerebral cortex and bulbus cinereus. The expression of selenoproteins has a hierarch while changing Se content, and Selenoprotein T (Selt), Selenoprotein K (Selk), Selenoprotein W (Selw), Selenoprotein U (Selu), Glutathione peroxidase 3 (Gpx3), Glutathione peroxidase 4 (Gpx4), Selenoprotein P (Sepp1), Selenoprotein O (Selo), Selenoprotein 15 (Sel15), Selenoprotein N (Seln), Glutathione peroxidase 2 (Gpx2) and Selenoprotein P 2 (Sepp2) take more necessary function in the chicken CNS. Therefore, we hypothesize that hierarchy of regulated the transcriptions of selenoproteome makes an important role of CNS Se metabolism and transport in birds.

Effects of Dietary Selenium on Inflammation and Hydrogen Sulfide in the Gastrointestinal Tract in Chickens.

Selenium (Se) is an essential trace element for humans and animals and is associated with many physiological functions. Previous studies have shown that low-Se diet may affect inflammatory cytokine productions and histology in the digestive system and that sulfide hydrogen (H2S) may contribute to the protection against tissue injury and the inhibition of inflammation in the gastrointestinal tract. In this study, we investigated the relationship between Se deficiency-induced inflammation and H2S production in the small intestine in chickens. One hundred twenty 1-day-old chickens were fed with diets with different Se concentrations (0.15mg/kg in the control and 0.028mg/kg in the low-Se-diet group). Chickens were euthanized and small intestinal tissues were extracted. We observed histology, measured H2S concentration, and evaluated the mRNA expression of H2S-producing enzymes cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MST), and inflammatory factors TNF-α, NF-κB p50, COX-2, and PTGES. Our results showed that chickens fed with low-Se diet exhibited histological changes, lower H2S production, and lower mRNA expression of H2S-producing enzymes (CSE, CBS, and 3-MST) whereas higher mRNA expression of intestinal inflammatory factors (TNF-α, NF-κB p50, COX-2, and PTGES) compared to controls. Our results indicate that low-Se diet could impact H2S, H2S-producing enzymes, and inflammatory factors in the small intestine, implying that Se is important in maintaining intestinal functions and H2S production is downregulated in Se deficiency-induced inflammation. The downregulation exacerbates the inflammation and impacts H2S-mediated intestinal functions.

Selenium (Se) Homeostasis in Chicken Central Nervous System Involves Selenoprotein Expression from Insufficient to Excess Se

Selenium (Se) incorporated in selenoproteins as selenocysteine and supports various important cellular and organismal functions. When Se deficient, brain present the first priority grade to get it. It becomes a homeostasis of Se content. We recently reported that O‐Phosphoseryl‐tRNA: selenocysteinyl‐tRNA synthase (SepSecS) plays an important role in Se homeostasis regulation in the avian brain (PloS One 7:e35761 (2012)). To better understand the relationship of Se homeostasis and selenoprotein expression in chicken central nervous system (CNS), day‐old HyLine White chickens were fed a low Se diet (Se‐L, 0.028 mg/g) supplemented with 4 levels of dietary Se (0 to 5.0 mg Se/kg) as Na2SeO3 for 8 wk. Then chickens were dissected for getting the CNS, which included cerebral contex, cerebellum, thalamus, bulbus cinereus and marrow. Se content in CNS was measured. The expression of selenoproteome which have 24 selenoproteins were detected by the qRT‐PCR array. Se homeostasis was observed during changed the content of Se in chicken CNS from insufficient to excess Se, especially in cerebral contex and bulbus cinereus. In cerebellum, the expression of SePP1 had augmented when Se content was abundant. It implied that SePP1 was the main Se transporters. In bulbus cinereus, the selenoprotein had increased obviously as the content of Se was 3.0 mg/kg. Furthermore, at the 5.0 mg/kg Se, there was a special increase about the selenoprotein expression in the marrow. The distribution of Se in chicken CNS is very notable. The expression of selenoproteins has a hierarch while changing Se content, and Selt, Selk, Selw, Selu, Gpx3, Gpx4, Sepp1, Selo, Sel15, Seln, Gpx2 and Sepp2 take more necessary function in the chicken CNS. In summary, hierarchy of regulated selenoprotein expression makes an important role of CNS Se metabolism and transport in avian.Support or Funding InformationChina New Century Excellent Talents in University (NECT‐1207‐02), China Program for New Century Excellent Talents In Heilongjiang Provincial University (1252‐NCET‐009), Doctor Initial Funding of Northeast Agricultural University (2012RBC52), Research Special funds for Scientific Innovation Talents of Haerbin (2012RFQXN006) and Science Foundation of the Education Department of Heilongjiang Province (12511031).

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.

Selenium Deficiency Affects the mRNA Expression of Inflammatory Factors and Selenoprotein Genes in the Kidneys of Broiler Chicks.

The aim of this study was to investigate the influence of Se deficiency on the transcription of inflammatory factors and selenoprotein genes in the kidneys of broiler chicks. One hundred fifty 1-day-old broiler chicks were randomly assigned to two groups fed with either a low-Se diet (L group, 0.033 mg/kg Se) or an adequate Se diet (C group, 0.2 mg/kg Se). The levels of uric acid (UA) and creatinine (Cr) in the serum and the mRNA levels of 6 inflammatory factors and 25 selenoprotein genes in the kidneys were measured as the clinical signs of Se deficiency occurred at 20 days old. The results indicated that the contents of UA and Cr in the serum increased in L group (p < 0.05), and the mRNA levels of the inflammatory factors (NF-κB, iNOS, COX-2, and TNF-α) increased in L group (p < 0.05). Meanwhile, the mRNA levels of PTGEs and HO-1 were not changed. In addition, 25 selenoprotein transcripts displayed ubiquitous expression in the kidneys of the chicks. The mRNA levels of 14 selenoprotein genes (Dio1, Dio2, GPx3, Sepp1, SelH, SelI, SelK, Sepn1, SelO, SelW, Sep15, SelT, SelU, and SelS) decreased, and 9 selenoprotein genes (GPx1, GPx2, GPx4, SelPb, Txnrd1, Txnrd2, Txnrd3, SPS2, and SelM) increased in L group (p < 0.05), but the Dio3 and Sepx1 mRNA levels did not change. The results indicated that Se deficiency resulted in kidney dysfunction, activation of the NF-κB pathway, and a change in selenoprotein gene expression. The changes of inflammatory factor and selenoprotein gene expression levels were directly related to the abnormal renal functions induced by Se deficiency.

Depletion of selenium in blood, liver and muscle from beef heifers previously fed forages containing high levels of selenium

Beef heifers which had grazed ‘Jose’ tall wheatgrass (TWG; Thinopyrum ponticum var. ‘Jose’; 10 heifers) and creeping wildrye (CWR; Leymus triticoides var. ‘Rio’; 10 heifers) with high levels of Se (>2mg/kg DM) due to growth in saline soils, accumulated high Se levels in blood, liver and muscle (Juchem et al., 2012). We determined the decrease in Se levels in blood, liver and muscle from these heifers, particularly the decrease of Se in muscle, in order to determine the maximum feeding length of a low Se diet (LSeD) required sustaining Se-enriched beef. Immediately after grazing, all heifers were fed a LSeD containing <0.30mg/kg DM for 209d. Blood, liver and muscle samples, as well as body weight (BW), were collected at the beginning and end of the LSeD feeding period and at intermediate times. After grazing, CWR and TWG heifers had similar BW, but TWG heifers had higher levels of Se in whole blood (1.19 versus 0.81mg/L), liver (2.67 versus 2.12mg/kg wet weight (WW)), and muscle tissue (0.87 versus 0.63mg/kg WW) than CWR heifers. The Se levels decreased with exposure time to the LSeD and, at 82d of feeding the LSeD, Se levels were 77 (liver), 49 (blood) and 31% (muscle) lower. The BW gains for both groups were ~0.5kg/d during the first 82d of feeding, but increased thereafter. Levels of Cu in serum (0.28 versus 0.50mg/L) and liver (1.14 versus 22.9mg/kg WW) were lower at the end of grazing in TWG heifers, and suggested a potential Cu deficiency. Grazing forages with high Se levels can result in Se-enriched beef, but a LSeD feeding period of <82d is required to maintain enrichment.

T-2 Toxin Alters the Levels of Collagen II and Its Regulatory Enzymes MMPs/TIMP-1 in a Low-Selenium Rat Model of Kashin-Beck Disease.

The objectives of this study are to assess T-2 toxin's involvement in low selenium (Se)-induced Kashin-Beck disease (KBD) in rats and unveil the mechanisms underlying this disease. Two hundred thirty rats were randomly divided into two groups after weaning and fed normal or low-Se diets (n=115), respectively, for a month. After low-Se model confirmation, rats in each group were subdivided into five: two subgroups (n=20) were fed their current diets (normal or low-Se diets, respectively) for 30 and 90days, respectively; two other subgroups (n=25) received their current diets + low T-2 toxin (100ng/g BW/day) for 30 and 90days, respectively; and 25 rats were fed their current diets + high T-2 toxin (200ng/g BW/day) for 30days. Articular cartilage samples were extracted for hematoxylin and eosin (H&E) staining and immunohistochemistry. Western blot and reverse transcription-polymerase chain reaction (RT-PCR) were used to assess protein and mRNA levels, respectively, of collagen II, matrix metalloproteinase (MMP-1), MMP -3, MMP-13, and tissue inhibitor of metalloproteinase-1 (TIMP-1). Low Se and T-2 toxin synergistically affected animal fitness. Interestingly, low Se + T-2 toxin groups showed KBD characteristics. MMP-1, -3, and -13 mRNA and protein levels generally increased in low-Se groups, while collagen II and TIMP-1 levels showed a downward trend, compared with normal diet fed animals for the same treatment (P<0.05). T-2 toxin's effect was dose but not time dependent. Low Se and T-2 toxin synergistically alter the expression levels of collagen II as well as its regulatory enzymes MMP-1, MMP-3, MMP-13, and TIMP-1, inducing cartilage damage. Therefore, T-2 toxin may cause KBD in low-Se conditions.

Abnormality of epiphyseal plate induced by selenium deficiency diet in two generation DA rats.

This study aimed to observe the effects of Se deficiency on epiphyseal plates of two generation DA rats fed with artificial total synthetic low Se diet. All F0 and F1 DA rats were fed with synthetic low Se diet (SeD group) and low Se diet supplied with Se (SeS group). The levels of selenium and enzyme activities of GPx were detected in plasma of the rats. General growth of bone and articular cartilage was measured macroscopically and microscopically. The epiphyseal plate of femur heads or tibia were obtained to histological and immunohistochemical examinations. The cartilage from left knee joints and femur heads was used to detect the gene expression of collagens, ADAMTSs and several selenoproteins by RT-qPCR. Two generation SeD rats showed Se insufficiency status. The thicknesses of the femur and tibial epiphyseal plates in both F0 and F1 SeD rats were significantly less than that of SeS rats. In F1 generation, SeD rats showed much fewer proliferative chondrocyte layers than SeS ones. Importantly, two generation SeD rats both showed significantly more serious pathological changes of epiphyseal plates. In two generation rats, gene expressions of COL II, GPx1 and GPx4 were significantly down-regulated in SeD rats than SeS ones; meanwhile ADAMTS-4 showed an up-regulated expression in cartilage. Dietary Se deficiency can apparently cause epiphyseal plate lesion and decrease cartilage type II collagen production and GPx1 activity in two generation DA rats fed with the artificial total synthesis low Se diet.

Changes in Growth and Feed Efficiency in Chickens Supplemented with Supernutritional and Excess Selenium are Associated with Changes in Appetite

Selenium (Se) is an essential nutrient for the chicken. We recently reported that both insufficient and excess Se decreased growth in chickens (Biol Trace Elem Res 159:174(2014)). Oral Se administration to Se‐deficient chickens has been reported to increase appetite within hours. To better understand the relationship of Se status with growth and appetite, 1‐day‐old Hy‐Line White chickens were fed a low Se diet (Se‐L, 0.028 mg/g) supplemented with 4 levels of dietary Se (0 to 5.0 mg Se/kg) as Na2SeO3 for 8 wk. Body weight (BW) and feed intake (FI) were decreased significantly by Se‐L and Se‐excess (Se‐E, 5.0 mg/kg) vs. Se‐adequate (Se‐A, 0.15 mg/kg), whereas Se‐supernutrition (Se‐S, 3.0 mg/kg) increased BW and FI as compared to Se‐A birds. FI relative to metabolic size (FI/BW0.67) of Se‐S birds was significantly higher than other groups. Se‐S lowered and Se‐E increased blood glucose relative to Se‐A and Se‐L birds. At 8 wk, gene expression of Neuropeptide Y (NPY) in hypothalamus was increased by Se‐S but leptin receptor (LEPR) mRNA levels were unchanged relative to Se‐A birds, suggesting that increased FI in Se‐S birds was due to increased appetite. In Se‐E birds, LEPR mRNA levels were increased at 8 wk, suggesting appetite was decreased in Se‐E birds. There were no differences in NPY or LEPR mRNA in Se‐L vs. Se‐A birds. In summary, these results demonstrate that changes in growth and feed efficiency with supernutritional Se and excess Se are associated with changes in appetite. Support: China NECT‐1207‐02; 1252‐NCET‐009 and 2012RBC52.

Genotoxic effects of two-generational selenium deficiency in mouse somatic and testicular cells.

Many studies have investigated genotoxic effects of high Se diets but very few have addressed the genotoxicity of Se deprivation and its consequences in germ cells and none in somatic cells. To address these data gaps, C57BL/6 male mice were subjected to Se deprivation starting in the parental generation, i.e. before conception. Mice were given a diet of either low (0.01mg Se/kg diet) or normal (0.23mg Se/kg diet) Se content. Ogg1-deficient (Ogg1 (-/-) ) mice were used as a sensitive model towards oxidative stress due to their reduced capacity to repair oxidised purines. Ogg1 (-/-) mice also mimic the repair characteristics of human post-meiotic male germ cells which have a reduced ability to repair such lesions. The genotoxicity of Se deficiency was addressed by measuring DNA lesions with the alkaline single cell gel electrophoresis (+ Fpg to detect oxidised DNA lesions) in somatic cells (nucleated blood cells and lung cells) and male germ cells (testicular cells). Total Se concentration in liver and GPx activity in plasma and testicular cells were measured. Gene mutation was evaluated by an erythrocyte-based Pig-a assay. We found that Se deprivation of F1 from their conception and until early adulthood led to the induction of DNA lesions in testicular and lung cells expressed as significantly increased levels of DNA lesions, irrespective of the mouse genotype. In blood cells, Se levels did not appear to affect DNA lesions or mutant cell frequencies. The results suggest that the testis was the most sensitive tissue. Thus, genotoxicity induced by the low Se diet in the spermatozoal genome has potential implications for the offspring.