SeMet Group Research Articles

Selenomethionine Supplementation Contributes to Reducing Oxidative Stress and Inflammation Markers following Exercise-Induced Muscle Damage

Background. Exercise-induced muscle damage (EIMD) is a temporary response to intense or prolonged exercise that can cause muscle pain, inflammation, and impaired muscle function. Antioxidant supplementation is a proposed strategy to reduce EIMD symptoms by targeting reactive oxygen and nitrogen species (RONS) involved in the process. Objective. The study aimed to investigate the effect of Selenomethionine supplementation on malondialdehyde (MDA) and C-reactive protein (CRP) levels resulting from Exercise-Induced Muscle Damage (EIMD). Materials and methods. This study used a randomized pretest-posttest control group design, involving a total of 32 male recreational students from the State University of Surabaya (Indonesian: Universitas Negeri Surabaya), (age 19.25 ± 0.76 years, body mass 63.16 ± 3.38 kg, height 167.28 ± 4.54 cm, body fat 19.60% ± 4.57%). The participants were randomly assigned to the selenomethionine group (SEM, 100 µg/day) or placebo group (PLA, corn starch 100 mg/day) for a period of 28 days (4 weeks). On days 1 (baseline) and 29, participants underwent a single bout of EIMD. Blood samples were collected 24 hours post-EIMD to measure MDA and CRP concentrations in plasma. The statistical analysis was conducted using paired sample t-test. Results. The placebo group experienced a significant increase in plasma MDA and CRP concentrations after EIMD compared with baseline values (p < 0.05). However, the SeMet group showed lower plasma MDA and CRP levels than the placebo group. Conclusions. Daily Selenomethionine supplementation for 28 days has been found to reduce oxidative stress by lowering MDA levels in the blood and to decrease inflammation by reducing CRP levels post-exercise-induced muscle damage. This indicates a lower risk of EIMD due to reduced oxidative stress and inflammation.

Selenomethionine alleviates decabromodiphenyl ether-induced oxidative stress and ferroptosis via the NRF2/GPX4 pathway in the chicken brain

Decabromodiphenyl ether (BDE209) is a toxic environmental pollutant that can cause neurotoxicity, behavioral abnormalities, and cognitive impairment in animals. However, the specific mechanisms of BDE209-induced neurological injury and effective preventative and therapeutic interventions are lacking. Even though selenomethionine (Se-Met) has a significant detoxification effect and protects the nervous system, it remains unclear whether Se-Met can counteract the toxic effects of BDE209. For the in vivo test, we randomly divided 60 1-week-old hy-line white variety chicks into the Con, BDE209, Se-Met, and BDE209 +Se-Met groups. In vitro experiments were performed, exposing chick embryo brain neurons to BDE209, Se-Met, N-Acetylcysteine (NAC, a ROS inhibitor), and RSL3 (a GPX4 inhibitor). We demonstrated that BDE209 induced oxidative stress and ferroptosis in the chicken brain, which mainly manifested as mitochondrial atrophy, cristae breakage, increased Fe2+ and MDA content, decreased antioxidant enzyme activity, and the inhibition of the NRF2/GPX4 signaling pathway in the brain neurons. However, Se-Met supplementation reversed these changes by activating the NRF2/GPX4 pathway, reducing mitochondrial damage, enhancing antioxidant enzyme activity, and alleviating ferroptosis. This study provides insight into the mechanism of BDE209-related neurotoxicity and suggests Se-Met as an effective preventative and control measure against BDE209 poisoning.

SeMet alleviates LPS-induced eggshell gland necroptosis mediated inflammation by regulating the Keap1/Nrf2/HO-1 pathway

Exposure to lipopolysaccharide (LPS) can lead to inflammation in a variety of tissues and organs. Selenium (Se) plays a crucial role in mitigating inflammatory damage. Compared with inorganic selenium, organic selenium, such as selenomethionine (SeMet), has the advantages of a higher absorption rate and lower toxicity in animals. This study examined the protective effects of SeMet on eggshell gland tissue damage caused by LPS. Hy-Line Brown laying hens were chosen as the experimental animals and were randomly assigned to four groups: control group (C), lipopolysaccharide group (LPS), SeMet group (Se), and SeMet + lipopolysaccharide group (Se + LPS). H&E staining and transmission electron microscope were performed to observe the pathological changes of eggshell glands, oxidative stress related indicators were measured using relevant kits, qRT‒PCR and western blotting were used to evaluate the mRNA and protein levels of the Nrf2 pathway, necroptosis, and inflammation related indicators. The results showed that LPS treatment increased the content of malondialdehyde (MDA), decreased the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX), and decreased the content of glutathione (GSH). LPS increased the levels of Keap1, RIPK1, RIPK3, MLKL, TNF-α, COX-2, and NF-κB, while decreasing the levels of HO-1, NQO1, Nrf2, and Caspase-8. However, SeMet treatment effectively reversed the changes of the above indicators, indicating that SeMet alleviates eggshell gland cell necroptosis-mediated inflammation induced by LPS via regulating the Keap1/Nrf2/HO-1 pathway. This study elucidated the mechanism by which SeMet alleviates LPS-induced eggshell gland tissue damage in Hy-Line Brown laying hens and provided a new direction for expanding the application of SeMet in the feeding and production of laying hens.

Selenomethionine Antagonized microRNAs Involved in Apoptosis of Rat Articular Cartilage Induced by T-2 Toxin.

T-2 toxin and selenium deficiency are considered important etiologies of Kashin-Beck disease (KBD), although the exact mechanism is still unclear. To identify differentially expressed microRNAs (DE-miRNAs) in the articular cartilage of rats exposed to T-2 toxin and selenomethionine (SeMet) supplementation, thirty-six 4-week-old Sprague Dawley rats were divided into a control group (gavaged with 4% anhydrous ethanol), a T-2 group (gavaged with 100 ng/g·bw/day T-2 toxin), and a T-2 + SeMet group (gavaged with 100 ng/g·bw/day T-2 toxin and 0.5 mg/kg·bw/day SeMet), respectively. Toluidine blue staining was performed to detect the pathological changes of articular cartilage. Three rats per group were randomly selected for high-throughput sequencing of articular cartilage. Target genes of DE-miRNAs were predicted using miRanda and RNAhybrid databases, and the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway were enriched. The network map of miRNA-target genes was constructed using Cytoscape software. The expression profiles of miRNAs associated with KBD were obtained from the Gene Expression Omnibus database. Additionally, the DE-miRNAs were selected for real-time quantitative PCR (RT-qPCR) verification. Toluidine blue staining demonstrated that T-2 toxin damaged articular cartilage and SeMet effectively alleviated articular cartilage lesions. A total of 50 DE-miRNAs (28 upregulated and 22 downregulated) in the T-2 group vs. the control group, 18 DE-miRNAs (6 upregulated and 12 downregulated) in the T-2 + SeMet group vs. the control group, and 25 DE-miRNAs (5 upregulated and 20 downregulated) in the T-2 + SeMet group vs. the T-2 group were identified. Enrichment analysis showed the target genes of DE-miRNAs were associated with apoptosis, and in the MAPK and TGF-β signaling pathways in the T-2 group vs. the control group. However, the pathway of apoptosis was not significant in the T-2 + SeMet group vs. the control group. These results indicated that T-2 toxin induced apoptosis, whereas SeMet supplementation antagonized apoptosis. Apoptosis and autophagy occurred simultaneously in the T-2 + SeMet group vs. T-2 group, and autophagy may inhibit apoptosis to protect cartilage. Compared with the GSE186593 dataset, the evidence of miR-133a-3p involved in apoptosis was more abundant. The results of RT-qPCR validation were consistent with RNA sequencing results. Our findings suggested that apoptosis was involved in articular cartilage lesions induced by T-2 toxin, whereas SeMet supplementation antagonized apoptosis, and that miR-133a-3p most probably played a central role in the apoptosis process.

Selenium Uptake, Translocation, and Metabolization Pattern during Barley Malting: A Comparison of Selenate, Selenite, and Selenomethionine.

Selenium (Se) is an essential trace element for human and animal health. Understanding the uptake and translocation of Se in crops is critical from the perspective of Se biofortification. In this study, barley was malted to investigate the uptake, translocation, and metabolism of exogenous Se including Na2SeO4, Na2SeO3, and selenomethionine (Se-Met). The results showed that the uptake rates of different forms of Se in barley decreased in the following order: Se-Met > Na2SeO3 > Na2SeO4, with the peak uptake occurring at the end of the steeping stages. In the early stages of germination, Se was mainly distributed in the husk and endosperm. Exogenous Se upregulated the transcription levels of Se transport and metabolic enzyme genes in the barley to varying degrees, which promoted Se transformation in various tissues, and improved Se bioeffectiveness. Compared to the Na2SeO3 and Se-Met groups, more Se was transferred from husk and endosperm to acrospire and rootlets in the Na2SeO4 group during the germination stage. Na2SeO4 and Se-Met stimulated the development of rootlets, and accelerated Se metabolism, resulting in a higher Se loss rate. Thus, these comparative findings provide new insights into Se uptake, transformation, and metabolization in barley.

Antitumor effect of selenium-rich Brazil nuts and selenomethionine dietary supplementation on pre-existing 4T1 mammary tumor growth in mice.

Selenium (Se) is an essential micronutrient known to play an important role in the antioxidant system that can potentially influence tumor growth. We aimed to investigate the effects of dietary Se supplementation after detection of 4T1 mammary tumor growth in BALB/c mice. Thirty female mice received subcutaneous inoculation of 4T1 cells. After five days, all animals presenting palpable tumors were randomly assigned to three groups: a control group (Se-control) receiving a diet with adequate Se (0.15 mg/kg) and two other groups that received Se-supplemented diets (1.4 mg/kg of total Se) with either Brazilian nuts (Se-Nuts) or selenomethionine (SeMet). Data were assessed by either One or Two-way ANOVA followed by Tukey's HSD or Bonferroni's post hoc tests, respectively. Both Se-supplemented diets reduced tumor volume from the thirteenth day of feeding compared with the Se-adequate (control) diet (p < 0.05). The SeMet group presented a higher Se blood concentration (p < 0.05) than the Se-control group, with the Se-Nuts group presenting intermediate values. Selenoprotein P gene expression in the liver was higher in the Se-Nuts group than in the Se-control group (p < 0.05), while the SeMet group presented intermediate expression. Dietary Se supplementation, starting after detection of 4T1 palpable lesions, reduced tumor volume in mice.

Protective Effect of SeMet on Liver Injury Induced by Ochratoxin A in Rabbits.

Ochratoxin A (OTA) is second only to aflatoxin in toxicity among mycotoxins. Recent studies have shown that selenomethionine (SeMet) has a protective effect on mycotoxin-induced toxicity. The purpose of this study was to investigate the protective effect and mechanism of SeMet on OTA-induced liver injury in rabbits. Sixty 35-day-old rabbits with similar body weight were randomly divided into five groups: control group, OTA group (0.2 mg/kg OTA), OTA + 0.2 mg/kg SeMet group, OTA + 0.4 mg/kg SeMet group and OTA + 0.6 mg/kg SeMet group. Rabbits were fed different doses of the SeMet diet for 21 d, and OTA was administered for one week from day 15 (the control group was provided the same dose of NaHCO3 solution). The results showed that 0.4 mg/kg SeMet could significantly improve the liver injury induced by OTA poisoning. SeMet supplementation can improve the changes in physiological blood indexes caused by OTA poisoning in rabbits and alleviate pathological damage to the rabbit liver. SeMet also increased the activities of SOD, GSH-Px and T-AOC and significantly decreased the contents of ROS, MDA, IL-1β, IL-6 and TNF-α, effectively alleviating the oxidative stress and inflammatory response caused by OTA poisoning. In addition, OTA poisoning inhibits Nrf2 and HO-1 levels, ultimately leading to peroxide reaction, while SeMet activates the Nrf2 signaling pathway and enhances the expression of the HO-1 downstream Nrf2 gene. These results suggest that Se protects the liver from OTA-induced hepatotoxicity by regulating Nrf2/HO-1 expression.

Study of selenomethionine on the selenoproteins expression in hepatocyte L02 and the synergistic effect of serine

To observe the effect of selenomethionine(SeMet)on the selenoproteins expression in hepatocyte L02 and the synergistic effect of serine. The L02 cells were cultured and divided into SeMet group and Serine+SeMet group. SeMet dose was set as 0. 001, 0. 01, 0. 1, 1 and 10 μmol/L. Serine and SeMet were mixed according to 2∶1 molar ratio(Serine∶SeMet=2∶1). The L02 cells were cultured for 48 h after SeMet and Serine added. Finally, the cell culture supernatants and homogenates were collected for the selenoprotein P(SEPP)and glutathione peroxidase 1(GPx1)concentrations detection by a double-antibody sandwich enzyme-linked immuno-sorbent assay(ELISA). The expression of SEPP and GPx1 in cell homogenates was detected by western blot(WB). ELISA and WB results showed that GPx1 and SEPP expressions were dose dependent in a low SeMet concentration range, reached their inflection points when SeMet concentration was 1 μmol/L and 0. 1 μmol/L respectively, and began to decrease when SeMet concentration was further increased to 10 μmol/L. WB result showed that serine had a synergistic effect on GPx1 and SEPP expressions as SeMet concentration was 0. 001 μmol/L to 10 μmol/L. There was an inflection point in selenium protein synthesis when SeMet acted on normal hepatocyte(L02), the specific mechanism needs to be further explored. Secondly, serine had a synergistic effect on GPx1 and SEPP expressions of SeMet in hepatocyte(L02).

Quantitative proteomic analysis reveals that the Rap1/MAPK/ERK pathway is inhibited through selenomethionine strengthening antioxidant activity.

To investigate the influence on the proteome of chicken skeletal muscles of Selenomethionine (SeMet) use, 36 chicks were fed with SeMet feeding for 35days. A total of 72 1-day old broiler chicks were randomly allocated into two groups (n = 36/group): the control group (C group), the SeMet supplemented group (SeMet group). The Selenium (Se) concentrations of skeletal muscles from the chicks with basaldiet (negative control group) and SeMet feeding were found to be 0.01mg/kg and 0.40mg/kg, respectively. The skeletal muscles from the two groups were investigated using isobaric Tags for Relative and Absolute Quantitation (iTRAQ), coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. This proteomic analysis identified proteins that were differentially expressed between the two groups. A total of 3564 proteins from the SeMet and the control (C) groups at 35days were analyzed. 86 proteins were found by iTRAQ to be differentially expressed in the SeMet group, including 38 up-regulated proteins and 48 down-regulated proteins. These differential proteins were later identified as being mainly involved in antioxidant and enzyme-regulating activities. Fluorescent quantitative PCR(qPCR) and Western blot analyse proved to be consistent with the results of iTRAQ identification. The differentially expressed proteins (DEPs) identified in our work could be specific biomarkers related to SeMet intake in chicks. SeMet intake may strengthen antioxidant activity through Rap1/mitogen-activated protein kinases (MAPK)/extracellular signal-regulated kinase (ERK) signal pathways.

Beneficial antioxidant status of piglets from sows fed selenomethionine compared with piglets from sows fed sodium selenite

BackgroundStudies in mammals proved dietary organic selenium (Se) being superior to inorganic Se regarding effects on growth performance, antioxidative status, immune response, and Se homeostasis. However, the picture of possible effects of different Se sources and – levels can be expanded. The present field study evaluated the effects on weight gain, hematological and selected biochemical variables as well as plasma concentrations of vitamin E (vitE), total Se and selenobiomolecules in piglets throughout the suckling period. MethodsPiglets were monitored from birth to 38 days of age (d). The mother sows’ diets were enriched with l-selenomethionine (SeMet-0.26 and -0.43 mg Se/kg feed) or sodium selenite (NaSe-0.40 and -0.60 mg Se/kg feed) from 1 month prior to farrowing until the end of lactation period. Piglets received pelleted feed supplemented with Se similarly to the sows’ diets from one week of age. Selenite at 0.40 mg Se/kg (NaSe-0.40) represents a common Se source and -level in pig feed and served as control diet. ResultsFrom 24d, piglets in SeMet-groups had higher mean body weight (BW) compared with piglets from sows fed NaSe-0.40. Furthermore, from five-d and above, piglets from sows fed NaSe-0.60 had significantly higher BW than offspring from sows fed NaSe-0.40. Neonatal piglets in group SeMet-0.43 had significantly lower red blood cell counts (RBC), hemoglobin (Hgb) and hematocrit (Hct) concentrations compared with piglets from sows fed with NaSe-0.40. Neonatal and 5d-old piglets in group SeMet-0.26 showed higher gamma-glutamyl transferase activity than piglets in group NaSe-0.40. From five d and above, group NaSe-0.60 excelled with increased specific hematological variables culminating at age 38d with increased Hct, mean corpuscular volume (MCV), and MC hemoglobin (MCH) as well as increased activities of aspartate transaminase and lactate dehydrogenase compared with the other groups. Generally, offspring in the SeMet groups had higher total Se-concentrations in plasma than those from sows fed selenite, and showed a dose-response effect on plasma Se-concentrations. Furthermore, SeMet-fed piglets had higher plasma levels of the selenoproteins (Sel) glutathione peroxidase 3 (GPx3) and SelP as well as selenoalbumin. Plasma vitE levels were significantly negatively correlated with RBC throughout trial period. ConclusionsMaternal supplementation with SeMet during gestation influenced hematology and clinical biochemistry in neonatal piglets in a different way than in offspring from sows receiving selenite enriched diets. Growth performance was positively influenced by both dietary Se source and Se level. Higher plasma levels of GPx3 observed in piglets receiving SeMet probably improved the protection against birth or growth related oxidative stress. These might prime the piglets for demanding situations as indicated by higher weight gain in offspring from sows fed with SeMet-supplemented diets. Our results on some enzyme activities might indicate that piglets fed NaSe-0.60 had to cope with increased levels of oxidative stress compared with those originating from sows fed SeMet or lower dietary levels of selenite. We assume that combining inorganic and organic Se sources in complete feed for breeding sows might be beneficial fro reproduction and the offspring’s performance.

Toxicity effects of different dietary selenium forms on sea cucumber, Apostichopus japonicus

This experiment was conducted to determine the toxicological effect of selenomethionine (Se-met) and bio-fermenting Selenium (Se-bio) supplementation with basal diet to investigate growth performance, bioaccumulation and non-specific immune function in sea cucumber, (Apostichopus japonicus). Three groups of sea cucumbers in triplicate were given basal diet or supplemented with selenium (Se) from Se-met or Se-bio for 30 days. No significant difference in survival was observed among three treatments, but both groups fed with Se exhibited significant inhibition in body weight gain, specific growth rate and protein efficiency ratio compared to control group, meanwhile, feed conversion rate was significantly (P < 0.05) higher than control group. The Se content in the body wall significantly (P < 0.05) increased in Se-treated animals as compared with the control group. Antioxidant enzyme activities (superoxide dismutase and total antioxidant capacity) were significantly (P < 0.05) lower in body wall of sea cucumber fed Se-met supplemented diet compared to other groups. Se-met group resulted in significantly lower level of lysozyme activity compared to the control group. Therefore, when comparing similar doses from different Se sources, responses in bioaccumulation and non-specific immune function were markedly greater in Se-met as opposed to Se-bio.

Antagonistic effects of different selenium sources on growth inhibition, oxidative damage, and apoptosis induced by fluorine in broilers

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

Effects of dietary organic, inorganic, and nanoparticulate selenium sources on growth, hemato-immunological, and serum biochemical parameters of common carp (Cyprinus carpio).

An 8-week feeding trial was conducted to compare the effects of supplementing (0.7mgkg-1) different dietary selenium (Se) sources including organic [selenomethionine (SeMet)], inorganic [sodium selenite (Na2SeO3)], and nanoparticulate Se (nano-Se) on physiological responses of common carp, Cyprinus carpio juveniles (9.7 ± 0.1g). Basal diet without Se supplementation used as control. Fish fed nano-Se supplemented diet had the highest weight gain (97.2 ± 10.8%) and feed efficiency ratio (42.4 ± 0.8%). Intestinal villi height was significantly taller in fish fed nano-Se diet than in the control group in both foregut and midgut sections. Serum glutathione peroxidase and superoxide dismutase activities were significantly higher in nano-Se and SeMet groups than in control and sodium selenite groups. Fish fed Se-supplemented diets had greater red blood cell counts and hematocrit and hemoglobin values than the control group (P < 0.05). Nano-Se and SeMet groups showed a significant increase in white blood cell counts, neutrophil percentage, and serum lysozyme activity than the other groups. Fish fed nano-Se diet had the highest serum hemolytic activity, total immunoglobulin, and total protein and albumin contents, as well as the lowest serum total cholesterol and low density lipoprotein levels (P < 0.05). Overall, significant improvements in growth performance, feed utilization, intestinal morphology, and hemato-immunological and serum biochemical parameters of common carp juveniles suggest nano-Se as an efficient source for providing dietary Se in this species.

Effects of selenium exposure on the hematology, innate immunity, and metabolic rate of yellow-bellied sliders (Trachemys scripta scripta).

Selenium (Se) is a naturally occurring essential element that can be toxic to vertebrates at high concentrations. Despite studies that have documented that wild reptile species can accumulate copious amounts of Se, little is known regarding specific toxicologic effects of Se. In this study, 70 juvenile yellow-bellied sliders (Trachemys scripta scripta) were exposed to one of three seleno-L-methionine (SetMet) treatments (control, n = 24; 15 mg/kg, n = 23; and 30 mg/kg, n = 23) via weekly oral gavage for 5 weeks. At the conclusion of the experiment, kidney, liver, muscle, and blood samples were collected for quantitative Se analysis. Turtles in the SeMet treatment groups accumulated significantly higher amounts of Se in all tissue types relative to controls (all p < 0.001). Turtles in the 30 mg/kg SeMet group also accumulated significantly higher amounts of Se compared to the 15 mg/kg group (all p < 0.001). Although toxicity thresholds for reptiles have not been established, Se concentrations in liver tissue from both SeMet treatment groups exceeded reported avian toxicity thresholds for liver tissue. Neither oxygen consumption nor innate bactericidal capacity were impacted by SeMet exposure. However, turtles in the 30 mg/kg SeMet group exhibited anemia, which has been reported in other vertebrates exposed to Se. Furthermore, juvenile T. s. scripta in the 30 mg/kg SeMet group experienced 17% mortality compared to 0% in the 15 mg/kg treatment and control groups. To our knowledge, this study is the first to report dose-dependent Se-associated anemia and mortality in a chelonian species.

IFNγ-Inducible Chemokines Decrease upon Selenomethionine Supplementation in Women with Euthyroid Autoimmune Thyroiditis: Comparison between Two Doses of Selenomethionine (80 or 160 μg) versus Placebo

Background: Several studies have suggested that selenium may influence the natural history of autoimmune thyroiditis (AIT). Recently, IFNγ-inducible chemokines (CXCL-9, -10 and -11) were shown to be elevated in AIT patients. Objective: This prospective, randomized, controlled study was conducted to evaluate the effect of two doses of selenomethionine (Semet; 80 or 160 µg/day) versus placebo in euthyroid women with AIT, in terms of reduction of anti-thyroid antibodies, CXCL-9, -10 and -11 and improvement of thyroid echogenicity, over 12 months. Patients and Methods: Sixty patients, aged 21-65 years, were equally randomized into 3 groups: placebo, 80 µg/day of Semet (80-Semet) or 160 µg/day of Semet (160-Semet). Results: Anti-thyroperoxidase antibody (TPOAb) levels remained unaffected by Semet supplementation; anti-thyroglobulin antibody levels showed a significant reduction in the 160-Semet and the placebo group at 12 months. No significant change in thyroid echogenicity, thyroid volume and quality of life was observed within and between the groups. Subclinical hypothyroidism was diagnosed in 2 patients of the placebo group versus 1 patient in each Semet group. Serum CXCL-9 and -10 were significantly reduced in both Semet groups at 6 and 12 months, while they remained unchanged or increased in the placebo group. CXCL-11, TNFα and IFNγ showed a transient decrease at 6 months in both Semet groups but returned nearly to the basal levels at 12 months. Conclusions: Semet supplementation had no positive effect on thyroid echogenicity or TPOAb in our patients. However, we observed a Semet-dependent downregulation of the IFNγ-inducible chemokines, especially CXCL-9 and -10, which may serve as helpful biomarkers in future selenium supplementation trials.

A randomized-controlled, double-blind study of the impact of selenium supplementation on thyroid autoimmunity and inflammation with focus on the GPx1 genotypes.

To analyze the impact of selenium supplementation on serum antiTPO levels and thyroid echogenicity in patients with CAT, evaluating the response in subgroups with different GPx1 genotypes. CAT patients (n=55) with positive antiTPO were randomized to selenomethionine (SeMet) 200μg daily (n=28) or placebo (n=27) for 3months. Assessments included GPx1 genotyping at baseline and serum levels of plasma selenium, erythrocyte GPx1 activity, antiTPO and thyroid echogenicity at baseline, and 3 and 6months. In the SeMet group, the increase in plasma levels of selenium and erythrocyte GPx1 activity was similar among patients with different GPx1 genotypes. In the overall cohort, patients randomized to SeMet showed a 5% decrease in antiTPO levels at 3months (p=non-significant) and 20% at 6months (p<0.001 versus 3months). In contrast, patients in the placebo group did not show significant changes in antiTPO levels at any time point. Subgroup analysis showed that patients with different GPx1 genotypes presented comparable responses in antiTPO levels and echogenicity index to SeMet. Selenium supplementation decreased serum antiTPO levels in CAT patients, with similar response among patients with different GPx1 genotypes.

Selenium Attenuates HPV-18 Associated Apoptosis in Embryo-Derived Trophoblastic Cells but Not Inner Cell Mass In Vitro.

Objectives. Human papillomaviruses (HPV) are associated with cell cycle arrest. This study focused on antioxidant selenomethionine (SeMet) inhibition of HPV-mediated necrosis. The objectives were to determine HPV-18 effects on embryonic cells and to evaluate SeMet in blocking HPV-18 effects. Methods. Fertilized mouse embryos were cultured for 5 days to implanted trophoblasts and exposed to either control medium (group 1), HPV-18 (group 2), combined HPV-18 and 0.5 µM SeMet (group 3), or combined HPV-18 and 5.0 µM SeMet (group 4). After 48 hrs, trophoblast integrity and, apoptosis/necrosis were assessed using morphometric and dual-stain fluorescence assays, respectively. Results. HPV-18 exposed trophoblasts nuclei (253.8 ± 28.5 sq·µ) were 29% smaller than controls (355.6 ± 35.9 sq·µ). Supplementation with 0.5 and 5.0 µM SeMet prevented nuclear shrinkage after HPV-18 exposure. HPV-18 infected trophoblasts remained larger with SeMet supplementation. HPV-18 decreased cell viability by 44% but SeMet supplementation sustained cell viability. Apoptosis was lower when SeMet was present. HPV-18 decreased inner cell mass (ICM) viability by over 60%. Conclusions. HPV-18 decreased nuclear size and trophoblast viability but these effects were attenuated by the antioxidant SeMet. SeMet blocked HPV-18 associated apoptosis process in trophoblasts but not ICM cells suggesting involvement of different oxidative stress pathways.

Effects of organic and inorganic selenium supplementation during late pregnancy on colostrum and serum Se status, performance and passive immunity in Merghoz goats

This study was conducted to determine the effects of organic and inorganic selenium (Se) supplementation during late pregnancy on serum Se status, colostrum, performance and passive immunity in Merghoz goats in Iran. Thirty Merghoz goats (30 ± 3 kg) were given the same basal diet containing 0.11 mg Se/kg DM and were randomly allocated to one of three dietary treatments in a randomised complete block design. Four weeks before the expected kidding, the basal diets were supplemented with 0 (control), 0.3 mg Se/head.day in the form of L-selenomethionin (Se-Met) and 0.3 mg Se/head.day in the form of sodium selenite. Blood samples were collected from the goats in three phases: (1) a couple of days before starting the supplementation; (2) before the expected kidding; and (3) on the day of kidding. Blood samples were also taken from the newborn kids from the jugular vein at birth and 7 days of age. The serum Se and immunoglobulin G (IgG) concentrations, the white blood cells (WBC) and differential leukocyte counts were measured. The reproductive parameters such as the number of kids born per kidding, total weight of kids born per goat mating, the pregnancy period and kid birthweights were determined. The results indicated that the serum Se concentration increased in supplemented goats compared with controls. The Se concentrations also significantly increased in the colostrum of treated goats (P &lt; 0.05). Similarly, serum Se concentrations in kids of treated goats were increased at birth. On the other hand, colostrum and daily milk production were not affected by Se supplementation. Likewise, the change in the mean serum IgG levels was not different among goats and kids (P &gt; 0.05). However, the WBC, neutrophil and lymphocyte counts were higher in the kids of goats in the Se-Met group compared with the control group on the day of birth and 7 days of age (P &lt; 0.05). It seemed that Se-Met could have influenced the lamb’s immunity at birth and 7 days of age. By contrast, selenite has not affected the performance and passive immunity in Merghoz goats.

Effects of selenomethionine and sodium selenite supplementation on meat quality, selenium distribution and antioxidant status in broilers

This study was conducted to investigate the effects of selenomethionine (Se-Met) and sodium selenite (SS) supplementation on meat quality, selenium (Se) distribution, and antioxidant status in broilers. A total of 360 seven-days-old Ross 308 broilers of an average body weight 162 &amp;plusmn; 0.59 g were randomly allotted to three treatments, each of which included three replications of 40 birds. The treatments included a control diet containing 0.04 mg Se/kg and other two diets that contained 0.15 mg Se/kg supplemented by SS or Se-Met. The experiment lasted for 42 days. Selenium supplementation improved (P &amp;lt; 0.05) the Hunter a value of breast muscle in 8 and 16 h and decreased (P &amp;lt; 0.05) the drip loss of breast muscle in 24 and 48 h. Both Se sources and exposed time significantly influenced (P &amp;lt; 0.01) the drip loss of breast muscle. Selenium and glutathione concentrations in serum and in the studied organs were significantly higher (P &amp;lt; 0.05) after dietary Se supplementation while the Se-Met group showed the highest value (P &amp;lt; 0.05). Glutathione peroxidase activity in serum and in the studied organs was also significantly elevated (P &amp;lt; 0.05) by dietary Se supplementation while SS increased the glutathione peroxidase activities in pancreas and breast muscle to a larger extent (P &amp;lt; 0.05) than did Se-Met. The addition of Se from either source caused a significant increase (P &amp;lt; 0.05) in superoxide dismutase activities in tissues (except for kidney) whereas the Se-Met group was more effective (P &amp;lt; 0.05) than the SS group in breast muscle. Selenium supplementation increased (P &amp;lt; 0.05) the total antioxidant capability in serum, liver, kidney and breast muscle while the Se-Met group proved to be more effective (P &amp;lt; 0.05) than the SS group except for kidney. The Se-supplemented diets had a lower (P &amp;lt; 0.05) malondialdehyde concentration in serum and in the studied organs but the effect was more pronounced (P &amp;lt; 0.05) when Se-Met was used except for the serum. These results indicated that Se-Met supplementation was more effective than SS supplementation for depositing Se in serum and tissues, enhancing the antioxidant status and reducing the drip loss of breast muscle.

A preoperative model evaluating the tissue effects of chemopreventive agents in low-volume prostate cancer

1007 Background: To identify and assess biomarkers modulated by prostate cancer chemopreventive agents, we created a model that, by exploiting the time between histologic diagnosis of prostate cancer and definitive therapy (prostatectomy), expedites tissue cross comparison and confronts the multifocality and multizonal heterogeneity of prostate cancer. Methods: Between February 2001 and April 2002, 48 presurgical patients were enrolled in a single-institution, randomized, double-blind trial of vitamin E (VE) and L-selenomethionine (SeMET) based on the framework of the ongoing Selenium and Vitamin E Cancer Prevention Trial. Patients were treated with 400 IU VE, 200 μg SeMET, a combination of VE and SeMET, or placebo for 3 to 6 weeks before prostatectomy. All patients also received a multivitamin and vitamin C 250 mg each day. Ex vivo simulated sextant biopsies on the radical prostatectomy specimen (RPS) were performed, and 36 of 39 evaluable patients had RPS sections that were suitable for pathologic evaluation. Blood components were collected at baseline and prior to prostatectomy. We derived an apoptotic index (AI) morphologically and a proliferation index (PI) by using immunohistochemistry and counting Ki-67-positive nuclei. Cells were counted and identified by cell type (normal and cancerous) and by zone (peripheral [PZ], transition [TZ], and central [CZ]). Results: In normal epithelial cells when the Wilcoxon rank sum test was used to compare AI and PI changes between groups, the AI was higher in the TZ than in the CZ, a difference independent of treatment effects (p = .01). Between the largest PZ and TZ tumor foci, a statistically significant difference in PI was observed (p = .006). Using a multiple linear regression model fitted for AI from the largest RPS PZ tumor focus, we found a statistically significant difference between the SeMET group and the placebo group (p = .02). Conclusions: Besides introducing new findings, the clinicopathologic model proved itself a platform for biomarker discovery by leveraging molecular technologies to full advantage, including serum protein profiling (Kim et al., CEBP 2005) and gene expression profiling of different cell types. Supported by NIH grant CA88761. No significant financial relationships to disclose.