Se-deficient Diet Research Articles

Upregulated expression of transforming growth factor-\u03b2 receptor I/II in an endemic Osteoarthropathy in China

BackgroundKashin–Beck disease (KBD) is a chronic, deforming, endemic osteochondropathy that begins in patients as young as 2–3 years of age. The pathogenesis of KBD remains unclear, although selenium (Se) deficiency and T-2 toxin food contamination are both linked to the disease. In the present study, we evaluated transforming growth factor-β receptor (TGF-βR I and II) levels in clinical samples of KBD and in pre-clinical disease models.MethodsHuman specimens were obtained from the hand phalanges of eight donors with KBD and eight control donors. Animal models of the disease were established using Sprague–Dawley rats, which were fed an Se-deficient diet for 4 weeks and later administered the T-2 toxin. Cartilage cellularity and morphology were examined by hematoxylin and eosin staining. Expression and localization of TGF-βRI and II were evaluated using immunohistochemical staining and western blotting.ResultsIn the KBD samples, chondral necrosis was detected based on cartilage cell disappearance and alkalinity loss in the matrix ground substance. In the necrotic areas, TGF-βRI and II staining were strong. Positive percentages of TGF-βRI and II staining were higher in the cartilage samples of KBD donors than in those of control donors. TGF-βRI and II staining was also increased in cartilage samples from rats administered T-2 toxin or fed on Se-deficient plus T-2 toxin diets.ConclusionTGF-βRI and II may be involved in the pathophysiology of KBD. This study provides new insights into the pathways that contribute to KBD development.

Effects of maternal and progeny dietary selenium supplementation on growth performance and antioxidant capacity in ducklings

This study evaluated the effects of selenium (Se) supplementation in maternal and offspring diets on performance and antioxidant capacity of ducklings aged from 0 to 2 wk. A total of 144 female Longyan duck breeders aged 22-wk were allotted into 2 treatments and fed a control diet or a 0.16 mg Se/kg supplemented diet. At 40-wk, 120 offspring from each treatment were divided into 2 groups, with 6 replicates of 10 birds. Using a 2 × 2 factorial design, ducklings from each maternal dietary treatment were assigned to a control diet or a 0.16 mg Se/kg supplemented diet from hatch to 2-wk. Compared with Se-deficient diet, maternal diet supplemented with 0.16 mg Se/kg increased the BW of hatchlings (P < 0.01). There were interactions between maternal and progeny diet with 0.16 mg Se/kg in BW of ducklings aged 2 wk and BW gain (BWG) as ducklings from maternal Se/progeny none treatment had the lightest BW and BWG (P < 0.01). Maternal diet with 0.16 mg Se/kg decreased plasma concentration of uric acid and insulin-like growth factor 1 (P < 0.01), and progeny diet supplemented with 0.16 mg Se/kg increased the activities of glutathione peroxidase 3 (GPx3) in plasma and glutathione peroxidase 1 in erythrocyte (P < 0.01). Maternal diet with 0.16 mg Se/kg increased (P < 0.05) the hepatic activity of total superoxide dismutase (T-SOD). Progeny diet supplemented with 0.16 mg Se/kg increased (P < 0.01) hepatic activity of GPx3 and decreased (P < 0.01) the hepatic concentration of malondialdehyde. Interactions were detected between maternal and progeny diet with 0.16 mg Se/kg in hepatic activity of T-SOD and maternal and progeny diet supplemented with Se displayed the highest hepatic activity of T-SOD (P < 0.05). Overall, Se supplementation in the diet of duck breeders and offspring increased the antioxidant capacity of ducklings. Maternal Se supplementation increased the BW of hatchlings, whereas maternal and progeny dietary Se supplementation did not affect the BWG of ducklings aged from 0 to 2 wk. Se supplementation with additional 0.16 mg/kg in the diet of duck breeders and offspring displayed beneficial effects particularly on the antioxidant capacity in ducklings.

Calcium overload and reactive oxygen species accumulation induced by selenium deficiency promote autophagy in swine small intestine.

Selenium (Se) deficiency can seriously affect the small intestine of swine, and cause diarrhea in swine. However, the specific mechanism of Se deficiency-induced swine diarrhea has rarely been reported. Here, to explore the damage of Se deficiency on the calcium homeostasis and autophagy mechanism of swine, in vivo and in vitro models of swine intestinal Se deficiency were established. Twenty-four pure line castrated male Yorkshire pigs (45 d old, 12.50 ± 1.32 kg, 12 full-sibling pairs) were divided into 2 equal groups and fed Se-deficient diet (0.007 mg Se/kg) as the Se-deficiency group, or fed Se-adequate diet (0.3 mg Se/kg) as the control group for 16 weeks. The intestinal porcine enterocyte cell line (IPEC-J2) was divided into 2 groups, and cultured by Se-deficient medium as the Se-deficient group, or cultured by normal medium as the control group. Morphological observations showed that compared with the control group, intestinal cells in the Se-deficiency group were significantly damaged, and autophagosomes increased. Autophagy staining and cytoplasmic calcium staining results showed that in the Se-deficiency group, autophagy increased and calcium homeostasis was destroyed. According to the reactive oxygen species (ROS) staining results, the percentage of ROS in the Se-deficiency group was higher than that in the control group in the in vitro model. Compared with the control group, the protein and mRNA expressions of autophagy-calcium-related genes including Beclin 1, microtubule-associated proteins 1A (LC3-1), microtubule-associated proteins 1B (LC3-2), autophagy-related protein 5 (ATG5), autophagy-related protein 12 (ATG12), autophagy-related protein 16 (ATG16), mammalian target of rapamycin (mTOR), calmodulin-dependent protein kinase kinase β (CAMKK-β), adenosine 5′-monophosphate-activated protein kinase (AMPK), sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA), and calpain in the Se-deficiency group were significantly increased which was consistent in vivo and in vitro (P < 0.05). Altogether, our results indicated that Se deficiency could destroy the calcium homeostasis of the swine small intestine to trigger cell autophagy and oxidative stress, which was helpful to explain the mechanism of Se deficiency-induced diarrhea in swine.

Selenium Deficiency Aggravates Heat Stress Pneumonia in Chickens by Disrupting the M1/M2 Balance

Selenium (Se) is an essential trace element found in the body. Se deficiency and M1/M2 imbalance are closely related to inflammation. Heat stress can decrease immune function and cause inflammation. In order to investigate whether Se deficiency can aggravate pneumonia caused by heat stress and the role of M1/M2 imbalance in the occurrence of pneumonia, 100 AA broilers were divided into two groups and fed the conventional diet (0.2mg/kg Se) and the Se-deficient diet (0.03mg/kg Se). After 40days of feeding, the normal feeding group was randomly divided into a control group and a heat stress group. At the same time, the Se-deficient diet feeding group was randomly divided into a low Se group and a low Se heat stress group, with 25 chickens in each group. The model was established by exposure at 40℃. Six hours later, broilers were euthanized, and their lung tissues were collected. Hematoxylin and eosin staining, immunofluorescence, quantitative real-time PCR, and western blotting were used to detect lung histopathological changes and the expression of M1/M2 markers, nuclear receptor-κB (NF-κB) pathway genes, and heat shock proteins. Meanwhile, the activity and content of oxidative stress-related indices were also detected. We found that the expression of interleukin-1β, interleukin-6, interleukin-12, and tumor necrosis factor-α was upregulated and the expression of interleukin-2, interleukin-10, and interferon-γ was downregulated. Immunofluorescence showed that the expression of CD16 was increased, the expression of CD163 was weakened, and the M1/M2 imbalance was present. In addition, the NF-κB pathway was activated by the increased expressions of heat shock proteins and oxidative stress. There was an increase in malondialdehyde, nitric oxide, and inducible nitric oxide synthase content, while the activity of total antioxidant capacity, glutathione peroxidase, catalase, and superoxide dismutase decreased, and the expression of NF-κB and cyclooxygenase-2 increased. These results suggest that low Se induces M1/M2 imbalance through oxidative stress activation of the NF-κB pathway and aggravates lung tissue inflammation caused by heat stress. This study offers a theoretical basis for exploring the pathogenesis of various kinds of inflammation induced by Se deficiency from the perspective of M1/M2 and provides a reference for the prevention of such diseases.

Selenoproteins Protect Against Avian Liver Necrosis by Metabolizing Peroxides and Regulating Receptor Interacting Serine Threonine Kinase 1/Receptor Interacting Serine Threonine Kinase 3/Mixed Lineage Kinase Domain-Like and Mitogen-Activated Protein Kinase Signaling.

Liver necroptosis of chicks is induced by selenium (Se)/vitamin E (VE) deficiencies and may be associated with oxidative cell damage. To reveal the underlying mechanisms of liver necrosis, a pool of the corn–soy basal diet (10 μg Se/kg; no VE added), a basal diet plus all-rac-α-tocopheryl acetate (50 mg/kg), Se (sodium selenite at 0.3 mg/kg), or both of these nutrients were provided to day-old broiler chicks (n = 40/group) for 6 weeks. High incidences of liver necrosis (30%) of chicks were induced by –SE–VE, starting at day 16. The Se concentration in liver and glutathione peroxidase (GPX) activity were decreased (P < 0.05) by dietary Se deficiency. Meanwhile, Se deficiency elevated malondialdehyde content and decreased superoxide dismutase (SOD) activity in the liver at weeks 2 and 4. Chicks fed with the two Se-deficient diets showed lower (P < 0.05) hepatic mRNA expression of Gpx1, Gpx3, Gpx4, Selenof, Selenoh, Selenok, Selenom, Selenon, Selenoo, Selenop, Selenot, Selenou, Selenow, and Dio1 than those fed with the two Se-supplemented diets. Dietary Se deficiency had elevated (P < 0.05) the expression of SELENOP, but decreased the downregulation (P < 0.05) of GPX1, GPX4, SELENON, and SELENOW in the liver of chicks at two time points. Meanwhile, dietary Se deficiency upregulated (P < 0.05) the abundance of hepatic proteins of p38 mitogen-activated protein kinase, phospho-p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, phospho-c-Jun N-terminal kinase, extracellular signal-regulated kinase, phospho-mitogen-activated protein kinase, receptor-interacting serine-threonine kinase 1 (RIPK1), receptor-interacting serine-threonine kinase 3 (RIPK3), and mixed lineage kinase domain-like (MLKL) at two time points. In conclusion, our data confirmed the differential regulation of dietary Se deficiency on several key selenoproteins, the RIPK1/RIPK3/MLKL, and mitogen-activated protein kinase signaling pathway in chicks and identified new molecular clues for understanding the etiology of nutritional liver necrosis.

Downregulation of Insulin-Like Growth Factor-1 Receptor Mediates Chondrocyte Death and Matrix Degradation in Kashin-Beck Disease.

To explore the relationship between insulin-like growth factor (IGF)-1R expression and the pathological progression of Kashin-Beck disease (KBD). KBD cartilage samples were collected from 5 patients. Additionally, T-2 toxin was administered to rats fed a selenium (Se)-deficient diet, and their knee joints were collected. Human C28/I2 chondrocytes and mouse hypertrophic ATDC5 chondrocytes were cultured in vitro and treated with T-2 toxin and Se supplementation. Subsequently, the cultured human and mouse chondrocytes were treated with the IGF-1R inhibitor, picropodophyllin. Chondrocyte death and caspase-3 activity were analyzed using flow cytometry and a specific kit, respectively. Protein and mRNA expression levels of IGF-1R and matrix molecules were measured using immunohistochemistry, western blotting, and quantitative real-time reverse transcription-polymerase chain reaction analyses. The cartilages from patients with KBD and T-2 toxin-treated rats on a Se-deficient diet showed significantly decreased expression of IGF-1R compared to cartilages from controls. T-2 toxin decreased IGF-1R mRNA and protein levels in both C28/I2 and hypertrophic ATDC5 chondrocytes in a dose-dependent manner; however, Se supplementation reduced the decrease of IGF-1R induced by T-2 toxin. Furthermore, inhibition of IGF-1R resulted in chondrocyte death of C28/I2 and hypertrophic ATDC5 chondrocytes, as well as decreased type II collagen expression and increased MMP-13 expression at the mRNA and protein levels. Downregulation of IGF-1R was associated with KBD cartilage destruction. Therefore, inhibition of IGF-1R may mediate chondrocyte death and extracellular matrix degeneration related to the pathological progression of KBD.

Selenium deficiency induces spleen pathological changes in pigs by decreasing selenoprotein expression, evoking oxidative stress, and activating inflammation and apoptosis

BackgroundThe immune system is one aspect of health that is affected by dietary selenium (Se) levels and selenoprotein expression. Spleen is an important immune organ of the body, which is directly involved in cellular immunity. However, there are limited reports on Se levels and spleen health. Therefore, this study established a Se-deficient pig model to investigate the mechanism of Se deficiency-induced splenic pathogenesis.MethodsTwenty-four pure line castrated male Yorkshire pigs (45 days old, 12.50 ± 1.32 kg, 12 full-sibling pairs) were divided into two equal groups and fed Se-deficient diet (0.007 mg Se/kg) or Se-adequate diet (0.3 mg Se/kg) for 16 weeks. At the end of the trial, blood and spleen were collected to assay for erythroid parameters, the osmotic fragility of erythrocytes, the spleen index, histology, terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) staining, Se concentrations, the selenogenome, redox status, and signaling related inflammation and apoptosis.ResultsDietary Se deficiency decreased the erythroid parameters and increased the number of osmotically fragile erythrocytes (P < 0.05). The spleen index did not change, but hematoxylin and eosin and TUNEL staining indicated that the white pulp decreased, the red pulp increased, and splenocyte apoptosis occurred in the Se deficient group. Se deficiency decreased the Se concentration and selenoprotein expression in the spleen (P < 0.05), blocked the glutathione and thioredoxin antioxidant systems, and led to redox imbalance. Se deficiency activated the NF-κB and HIF-1α transcription factors, thus increasing pro-inflammatory cytokines (IL-1β, IL-6, IL-8, IL-17, and TNF-α), decreasing anti-inflammatory cytokines (IL-10, IL-13, and TGF-β) and increasing expression of the downstream genes COX-2 and iNOS (P < 0.05), which in turn induced inflammation. In addition, Se-deficiency induced apoptosis through the mitochondrial pathway, upregulated apoptotic genes (Caspase3, Caspase8, and Bak), and downregulated antiapoptotic genes (Bcl-2) (P < 0.05) at the mRNA level, thus verifying the results of TUNEL staining.ConclusionsThese results indicated that Se deficiency induces spleen injury through the regulation of selenoproteins, oxidative stress, inflammation and apoptosis.

Dietary Selenium Deficiency and Excess Accelerate Ubiquitin-Mediated Protein Degradation in the Muscle of Rainbow Trout (Oncorhynchus mykiss) via Akt/FoxO3a and NF-κB Signaling Pathways.

Selenium (Se) deficiency and excess can lead to protein degradation in fish. However, the underlying mechanisms remain unclear. Ubiquitin proteasome system (UPS) is the main pathway of muscle proteolysis. This study aimed to investigate the effect and molecular mechanism of dietary Se on ubiquitin-mediated muscle protein degradation in rainbow trout (Oncorhynchus mykiss). The fish were fed with the Se-deficient diet (0 mg/kg, DSe), Se-adequate diet (4 mg/kg, ASe), and Se-excessive diet (16 mg/kg, ESe), respectively. After a 10-week feeding trial, the growth performance, body composition, antioxidant enzyme activities, and UPS-related gene and protein expressions were detected. Results indicated that DSe and ESe diets significantly decreased the weight gain rate, specific growth rate, feed efficiency, and muscle crude protein content compared with ASe diet. The histological analysis showed that the mean diameter of muscle fibers was significantly decreased in DSe and ESe groups. And DSe and ESe diets significantly increased the contents of malondialdehyde and nitric oxide, but reduced the glutathione peroxidase activity. Additionally, the abundance of muscle ubiquitinated proteins and the expression levels of MuRF1 and Atrogin-1 were significantly increased in DSe and ESe groups. Compared to ASe diet, DSe and ESe diets significantly decreased the phosphorylation level of Akt Ser473 and the ratio of p-FoxO3a/FoxO3a, but significantly increased the phosphorylation level of IκBα and upregulated the expressions of TNF-α, IL-8, and NF-κB. Overall, this study indicated that dietary Se deficiency and excess accelerated the ubiquitin-mediated muscle protein degradation through regulating Akt/FoxO3a and NF-κB signaling pathways in rainbow trout.

Selenium Deficiency Leads to Changes in Renal Fibrosis Marker Proteins and Wnt/β-Catenin Signaling Pathway Components.

Renal fibrosis is the final result of the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD). Earlier studies confirmed that selenium (Se) displays a close association with kidney diseases. However, the correlation between Se and fibrosis has rarely been explored. Thus, this article mainly aimed to investigate the effect of Se deficiency on renal fibrosis and the Wnt/β-catenin signaling pathway. Twenty BALB/c mice were fed a diet containing 0.02-mg/kg Se (Se-deficient diet) or 0.18-mg/kg Se (standard diet) for 20 weeks. A human glomerular mesangial cell (HMC) cell line was transfected with lentiviral TRNAU1AP-shRNA vector to establish a stable Se deficiency model in vitro. As indicated in this study, the glutathione (GSH) content in the Se-deficient group displayed an obvious decline compared with that in the control group, whereas the content of malondialdehyde (MDA) was obviously elevated. The results of Masson staining showed fibrosis around the renal tubules, and the results of immunohistochemistry showed that the area of positive fibronectin expression increased. In the Se-deficient group, the levels of collagen I, collagen III, matrix metalloproteinase 9 (MMP9), and other fibrosis-related proteins changed significantly in vivo and in vitro. Compared with the control group, the TRNAU1AP-shRNA group showed markedly reduced cell proliferation and migration abilities. Our data indicate that Se deficiency can cause kidney damage and renal fibrosis. Furthermore, the Wnt pathway is critical for the development of tissue and organ fibrosis. The data of this study demonstrated that the expression of Wnt5a, β-catenin, and dishevelled 1 (Dvl-1) was significantly upregulated in the Se-deficient group. Therefore, the Wnt/β-catenin pathway may play an important role in renal fibrosis caused by Se deficiency.

Neonatal Selenoenzyme Expression Is Variably Susceptible to Duration of Maternal Selenium Deficiency.

Maternal selenium (Se) deficiency is associated with decreased neonatal Se levels, which increases the risk for neonatal morbidities. There is a hierarchy to selenoprotein expression after Se deficiency in adult rodents, depending on the particular protein and organ evaluated. However, it is unknown how limited Se supply during pregnancy impacts neonatal selenoprotein expression. We used an Se-deficient diet to induce perinatal Se deficiency (SeD), initiated 2–4 weeks before onset of breeding and continuing through gestation. Neonatal plasma, liver, heart, kidney, and lung were collected on the day of birth and assessed for selenoproteins, factors required for Se processing, and non-Se containing antioxidant enzymes (AOE). Maternal SeD reduced neonatal circulating and hepatic glutathione peroxidase (GPx) activity, as well as hepatic expression of Gpx1 and selenophosphate synthetase 2 (Sps2). In contrast, the impact of maternal SeD on hepatic thioredoxin reductase 1, hepatic non-Se containing AOEs, as well as cardiac, renal, and pulmonary GPx activity, varied based on duration of maternal exposure to SeD diet. We conclude that the neonatal liver and circulation demonstrate earlier depletion in selenoenzyme activity after maternal SeD. Our data indicate that prolonged maternal SeD may escalate risk to the neonate by progressively diminishing Se-containing AOE across multiple organs.

Low-Se Diet Can Affect Sperm Quality and Testicular Glutathione Peroxidase-4 activity in Rats.

This study aimed to observe the influence of selenium (Se) deficiency on sperm quality and selenoprotein expression in rats. Four-week male Wista rats were randomly divided into three groups: Se-A, Se-L, and Se-D (respectively for Se- adequate, low, and deficient group). After 9 weeks, the rats were sacrificed by anesthesia, with the cauda epididymidis quickly fetched for sperm count, motility, and deformity. Meanwhile the blood, liver, brain, heart, and testis were collected for Se and biochemical analysis. It was found that the rats in Se-D had poor growth, while the Se concentrations in blood, liver, and heart for Se-D decreased significantly, compared with Se-A and Se-L (p < 0.01). But no significant difference was observed in testis and brain and also no statistical significance for sperm count. The sperm motility for Se-A (63.07%) was significantly higher than Se-L (53.91%) and Se-D (54.15%). Deformities were observed in both Se-L and Se-D. Both glutathione peroxidases (GPxs) and selenoprotein-P (SEPP1) levels in plasma and tissues of Se-D were significantly lower than those of Se-A and Se-L (p < 0.01). The SEPP1 levels in heart and brain of Se-L were lower than Se-A (p < 0.01). There was no statistical difference for GPx1 between Se-A and Se-L. The GPx4 level in testis of Se-L was lower than Se-A (p < 0.05). However, the SEPP1 in plasma, liver, testis, and the GPx3 level in plasma of Se-L were higher than those of Se-A (p < 0.05 or p < 0.01). Our results show that dietary Se deficiency could reduce GPx4 and SEPP1 expression in testis, which further influence sperm motility and may cause sperm deformity. Selenoprotein expression in some tissues of Se-L was higher than that of Se-A, but sperm quality and GPx4 expression in testis were not improved for Se-L. Low active pseudoselenoproteins might be synthesized in low-Se condition. The underlying mechanism needs to be further investigated.

Dietary Se deficiency dysregulates metabolic and cell death signaling in aggravating the AFB1 hepatotoxicity of chicks

The objective of this study was to use isobaric tags for relative and absolute quantitation (iTRAQ) proteomic technology to systematically analyze the hepatotoxic mechanism of aflatoxin B1 (AFB1) and its prevention by Se in broilers. Four groups of day-old broilers were allocated into a 2 × 2 factorial design trial that fed a Se-deficient based diet (BD) or the BD + 1.0 mg AFB1/kg, 0.3 mg Se/kg, or 1.0 mg AFB1/kg plus 0.3 mg Se/kg for 3 wk. Dietary AFB1 increased serum ALT and decreased total protein and albumin concentrations, and induced hepatic histopathological lesions in Se adequate groups. Notably, Se deficiency exacerbated these AFB1-induced changes. Furthermore, Se deficiency reduced hepatic glutathione peroxidase but increased thioredoxin reductase and glutathione S-transferase activities and 8-hydroxydeoxyguanosine concentration in AFB1 administrated groups. Moreover, AFB1 dysregulated 261 co-differentially expressed proteins (DEPs) in both Se adequate and deficiency diets, and Se deficiency dysregulated 64 DEPs in AFB1 administrated diets. These DEPs are mainly related to phase I and II metabolizing enzymes, heat shock proteins, DNA repair, fatty acid metabolism and apoptosis. The in vitro study has verified that aldo-keto reductase family1, member10 plays an important role in AFB1-induced hepatotoxicity and Se-mediated detoxification of AFB1 in a chicken leghorn male hepatoma cells. Conclusively, this study has analyzed the hepatic proteome response to dietary AFB1 and Se, and thus shed new light on the mechanisms of hepatotoxicity of AFB1 and its detoxification by Se in broilers.

Se deficiency induces renal pathological changes by regulating selenoprotein expression, disrupting redox balance, and activating inflammation.

Selenium (Se) is closely associated with kidney disease, and renal injury often occurs together with hyposelenemia. This study was designed to reveal the mechanism underlying renal injury induced by Se deficiency in pigs. Twenty-four castrated male Yorkshire pigs were divided into two groups fed either a Se-deficient diet (0.007 mg Se per kg) or a Se-adequate diet (0.3 mg Se per kg). Serum and kidney samples were collected at the 16th week of the trial, processed, and analyzed for serum biochemistry, Se concentration, kidney index markers, histology, selenoprotein mRNA expression, redox status, and inflammatory cytokines. Dietary Se deficiency induced kidney injury, decreased (P < 0.05) Se concentrations, and increased (P < 0.05) kidney index and serum blood urea nitrogen, creatinine, and carbon dioxide values. Histological analysis indicated that Se deficiency induced inflammatory lesions and renal tubular atrophy in the renal medulla. Se deficiency downregulated (P < 0.05) nine selenoprotein genes (GPX1, SELENOW, SELENOH, SELENOP, GPX3, TXNRD2, SELENOI, SELENON, and SELENOM) and upregulated (P < 0.05) SEPHS2 in the kidneys. Se deficiency decreased (P < 0.05) the activity of glutathione peroxidase, thioredoxin reductase, and catalase, as well as the hydroxyl radical inhibition capacity, and increased (P < 0.05) the content of malondialdehyde and nitric oxide. Se deficiency increased (P < 0.05) the expression of the transcription factors NF-κB and HIF-1α, and regulated inflammatory cytokines. Se deficiency increased (P < 0.05) the expression of IL-6, IL-8, IL-12, IL-17, and cyclooxygenase-2, and decreased (P < 0.05) the expression of IL-10, IL-13, and TGF-β. These results indicated that Se deficiency induces kidney injury through the regulation of selenoproteins, oxidative stress, and inflammation.

Dietary selenium deficiency and supplementation differentially modulate the expression of two ER-resident selenoproteins (selenoprotein K and selenoprotein M) in the ovaries of aged mice: Preliminary data

In the present report, we determined the impact of dietary selenium (Se) deficiency and supplementation on the expression of two ER-resident selenoproteins i.e., Selenok and Selenom in the ovaries of aging mice. The mRNA expression of Selenok and Selenom (RT-qPCR) was significantly higher in the ovaries of mice fed diets supplemented with inorganic (ISe-S: 0.33 mg Se/kg) and organic (OSe-S: 0.33 mg Se/kg) Se compared to those fed a Se-deficient (Se-D: 0.08 mg Se/kg) diet and both Se-adequate (ISe-A: 0.15 mg Se/kg and OSe-A: 0.15 mg Se/kg) diets. Similarly, the protein signals of SELENOK (immunofluorescence assay) were also significantly higher in the Se-supplemented groups compared to those fed Se-D and Se-adequate (ISe-A and OSe-A) diets. Meanwhile, the rate of in vitro-produced blastocysts developing from MII oocytes was also evaluated and it was revealed that this rate was significantly higher in the Se-supplemented mice compared to those fed a Se-D diet. Altogether, the dietary Se supplementation increased the expression of Selenok (also its protein expression) and Selenom in the ovaries of aging mice, potentially contributing to an improved developmental potential of in vitro-matured M II oocytes.

Selenium deficiency induced necroptosis, Th1/Th2 imbalance, and inflammatory responses in swine ileum.

Selenium (Se) deficiency has a significant impact on the swine breeding industry by inducing digestive system damage and diarrhea. However, the molecular mechanism remains unclear. Our objectives were to investigate if different amounts of necroptosis, inflammatory responses, and T helper cell 1/T helper cell 2 (Th1/Th2) imbalances were induced by Se deficiency in intestinal porcine jejunal epithelial cells (IPEC-J2) and swine ileum tissue. Therefore, Se-deficient models were successfully established both in vitro and in vivo. In the current study, the cell morphological observation results showed that Se deficiency seriously affected the growth and differentiation of IPEC-J2 cells. Moreover, the necroptosis staining and histomorphology observation results showed that the number of necroptotic cells increased significantly, and the ileal tissue exhibited abnormal structures, including necroptotic features and inflammatory cell infiltration, in the Se-deficient group. Furthermore, Se deficiency resulted in accelerated cell necroptosis by increasing (p < .05) the expression of genes related to the tumor necrosis factor-α pathway at both the protein and messenger RNA (mRNA) levels compared to the control group. Moreover, the relative mRNA and protein expression of the inflammatory genes and their responses to dietary Se deficiency were consistent with the resultant Th1/Th2 imbalances in vitro and in vivo. Taken together, the results suggested that Se deficiency caused necroptosis, inflammatory responses, and abnormal expression of cytokines in swine ileum tissue. These findings might help us to explain the damage induced by Se deficiency to the digestive system of swine.

Renal changes and apoptosis caused by subacute exposure to Aroclor 1254 in selenium-deficient and selenium-supplemented rats.

Aroclor 1254 (A1254), a mixture of polychlorinated biphenyls, exerts hepatic, renal, and reproductive toxicity in rodents. This study aimed to determine a protective role of selenium on histopathological changes, oxidative stress, and apoptosis caused by A1254 in rat kidney. It included a control group, which received regular diet containing 0.15 mg/kg Se (C), a Se-supplemented group (SeS) receiving 1 mg/kg Se, a Se-deficient group (SeD) receiving Se-deficient diet of ≤0.05 mg/kg Se, an A1254-treated group (A) receiving 10 mg/kg of Aroclor 1254 and regular diet, an A1254-treated group receiving Se-supplementation (ASeS), and an A1254-treated group receiving Se-deficient diet (ASeD). Treatments lasted 15 days. After 24 h of the last dose of A1254, the animals were decapitated under anaesthesia and their renal antioxidant enzyme activities, lipid peroxidation (LP), glutathione, protein oxidation, and total antioxidant capacity levels measured. Histopathological changes were evaluated by light and electron microscopy. Apoptosis was detected with the TUNEL assay. Kidney weights, CAT activities, and GSH levels decreased significantly in all A1254-treated groups. Renal atrophic changes and higher apoptotic cell counts were observed in the A and ASeD groups. Both groups also showed a significant drop in GPx1 activities (A – 34.92 % and ASeD – 86.46 %) and rise in LP (A – 30.45 % and ASeD – 20.44 %) vs control. In contrast, LP levels and apoptotic cell counts were significantly lower in the ASeS group vs the A group. Histopathological changes and renal apoptosis were particularly visible in the ASeD group. Our findings suggest that selenium supplementation provides partial protection against renal toxicity of Aroclor 1254.

Selenosugars Are the Major Selenometabolites in Liver of Turkeys Fed High Selenium

Abstract Objectives Liver and other tissues accumulate selenium (Se) when animals are supplemented with high dietary Se as inorganic Se. Because the nature of this accumulated Se is not well characterized, we studied selenometabolomics in Se-deficient, Se-adequate, and high-Se liver. Methods Turkey poults were fed 0, 0.4, and 5 μg Se/g diet as Na2SeO3 in a Se-deficient (0.005 μg Se/g) diet for 28 days, and the effects of Se status determined using HPLC-ICP-MS and HPLC-ESI-MS/MS. Results In liver from turkeys fed a true Se-deficient diet and supplemented with inorganic Se (selenite), no selenomethionine (SeMet) was detected showing that the turkey cannot synthesize SeMet de novo from inorganic Se. Selenocysteine (Sec) was also below the level of detection in Se-deficient turkey liver, as expected in animals with negligible selenoprotein levels. Sec content in liver of turkeys fed high Se only doubled compared with Se-adequate liver, indicating that the 6-fold incryscease in liver Se in these birds was not due to increases in selenoproteins. What increased dramatically in high Se liver were the low molecular weight (MW) selenometabolites, glutathione-, cysteine- and methyl- conjugates of the selenosugar, seleno-N-acetyl galactosamine (SeGalNac). In addition, size-exclusion chromatography and followup analysis demonstrated that a substantial amount of Se in Se-adequate liver was present as selenosugars decorating general proteins via mixed-disulfide links, in addition to Sec-containing selenoproteins. In high-Se liver, these “selenosugar-decorated” proteins comprised ∼50% of the Se in the water-soluble fraction, in addition to the low MW selenometabolites. Conclusions In Se-adequate liver, far more Se is present as the selenosugar moiety, mostly decorating general proteins, than is present as Sec in selenoproteins. With high Se supplementation, increased selenosugar formation occurs, further increasing selenosugar-decorated proteins, but also increasing selenosugar linked to low MW thiols, leading to the formation of methyl-SeGalNac. This suggested pathway, underlying adaptation to high Se status in animals, needs further investigation including study of the potential of selenosugar compounds as biomarkers of high Se status. Funding Sources USDA, Hatch project 1,004,389, and by the Wisconsin Alumni Foundation, Selenium Nutrition Research Fund 12,046,295.

Dietary Selenium Deficiency Facilitated Reduced Stomatin and Phosphatidylserine Externalization, Increasing Erythrocyte Osmotic Fragility in Mice.

Selenium (Se) is an essential trace element that maintains normal physiological functions in organisms. Since the discovery of glutathione peroxidase (GSH-PX), public interest in selenoproteins has gradually increased. Based on previous studies, dietary Se maintains erythrocyte homeostasis through selenoprotein-induced mediation of redox reactions. Furthermore, both the surface phosphatidylserine (PS) and intramembrane stomatin contents can be used as indicators of erythrocyte osmotic fragility. This study focused on the mechanism by which dietary Se deficiency increases erythrocyte osmotic fragility. We fed Se-deficient grain to mice for 8weeks to establish a Se deficiency model in mice. We measured Se levels in the blood as well as the activities of antioxidant enzymes associated with selenoproteins in a Se-deficient environment. We used Western blotting, routine blood analysis, and other methods to detect red blood cell oxidative stress levels, membrane stomatin levels, and PS externalization. Fresh blood was collected to test erythrocyte osmotic fragility. The results showed that antioxidant enzyme activity was affected by dietary Se deficiency. Oxidative stress increased lipid peroxidation and the ROS content in the blood of the mice. Under such conditions, decreased PS exposure and stomatin content in the erythrocyte membrane eventually affected the structure of the erythrocyte membrane and increased erythrocyte osmotic fragility.

Selenium Deficiency-Induced Pancreatic Pathology Is Associated with Oxidative Stress and Energy Metabolism Disequilibrium.

Selenium (Se) is an essential micronutrient that plays a crucial role in development and physiological processes. The present study aimed to investigate the effects of Se deficiency on pancreatic pathology and the potential mechanism in pigs. Twenty-four castrated male Yorkshire pigs were divided into two groups and fed a Se-deficient diet (0.007mgSe/kg) or a Se-adequate diet (0.3mgSe/kg) for 16weeks. The serum concentrations of insulin and glucagon, Se concentration, histologic characteristics, apoptotic status, antioxidant activity, free radical content, and major metabolite concentrations were analyzed. The results showed that Se deficiency reduced the concentrations of insulin and glucagon in the serum and of Se in pancreas, decreased the number of islets and cells in the local islets, and induced pancreatic apoptosis. Se deficiency caused a redox imbalance, which led to an increase in the content of free radicals and decreased the activity of antioxidant enzymes. Of 147 targeted metabolites judged to be present in pancreas, only hypotaurine and D-glucuronic acid had differential concentrations with the false discovery rate < 0.05. Pathway analysis using metabolites with differential expression (unadjusted P < 0.05, fold change > 1.4 or < 0.67) found that 8 glycolytic metabolites were significantly increased by Se-deficient, whereas most of the tricarboxylic acid cycle and pentose phosphate pathway metabolites were not significantly changed. Our studies indicated that Se deficiency-induced pancreatic pathology was associated with oxidative stress and enhanced activity of glycolysis, which may provide gaining insight into the actions of Se as a diabetogenic factor.

Identification and determination of selenocysteine, selenosugar, and other selenometabolites in turkey liver.

Liver and other tissues accumulate selenium (Se) when animals are supplemented with high dietary Se as inorganic Se. To further study selenometabolites in Se-deficient, Se-adequate, and high-Se liver, turkey poults were fed 0, 0.4, and 5 μg Se g-1 diet as Na2SeO3 (Se(iv)) in a Se-deficient (0.005 μg Se g-1) diet for 28 days, and the effects of Se status determined using HPLC-ICP-MS and HPLC-ESI-MS/MS. No selenomethionine (SeMet) was detected in liver in turkeys fed either this true Se-deficient diet or supplemented with inorganic Se, showing that turkeys cannot synthesize SeMet de novo from inorganic Se. Selenocysteine (Sec) was also below the level of detection in Se-deficient liver, as expected in animals with negligible selenoprotein levels. Sec content in high Se liver only doubled as compared to Se-adequate liver, indicating that the 6-fold increase in liver Se was not due to increases in selenoproteins. What increased dramatically in high Se liver were low molecular weight (MW) selenometabolites: glutathione-, cysteine- and methyl-conjugates of the selenosugar, seleno-N-acetyl galactosamine (SeGalNac). Substantial Se in Se-adequate liver was present as selenosugars decorating general proteins via mixed-disulfide bonds. In high-Se liver, these "selenosugar-decorated" proteins comprised ∼50% of the Se in the water-soluble fraction, in addition to low MW selenometabolites. In summary, more Se is present as the selenosugar moiety in Se-adequate liver, mostly decorating general proteins, than is present as Sec in selenoproteins. With high Se supplementation, increased selenosugar formation occurs, further increasing selenosugar-decorated proteins, but also increasing selenosugar linked to low MW thiols.