SeMet Supplementation Research Articles

Effects of n-3 polyunsaturated fatty acids and selenomethionine supplementation on physicochemical properties, oxidative stability and endogenous enzyme activities of fresh pork loin

This study evaluated the physicochemical properties, oxidative stability, and endogenous enzyme activities in fresh pork loin from pigs fattened by supplementation of 3 % soybean oil (control), 3 % linseed oil or 3 % linseed oil combined with 0.3 mg/kg selenomethionine (SeMet). Both linseed oil treatments led to higher n-3 polyunsaturated fatty acids (PUFA) levels, lower L* values, n-6/n-3 ratios, and lipoxygenase activity compared to the control (P < 0.001). Supplementation with linseed oil alone reduced a*, n-6 PUFA, saturated and monounsaturated fatty acids, and GPx activity in pork loin compared to other treatments (P < 0.05). Adding SeMet decreased neutral lipase activity but did not affect a* or GPx activity (P > 0.05), likely due to the antioxidant property of SeMet. Overall, linseed oil and SeMet supplementation is a promising strategy to significantly increase n-3 PUFA content in pork without compromising color properties or oxidative stability.

Selenomethionine alleviates kidney necroptosis and inflammation by restoring lipopolysaccharide-mediated mitochondrial dynamics imbalance via the TLR4/RIPK3/DRP1 signaling pathway in laying hens

Selenomethionine (SeMet) is a beneficial organic source of selenium that is extensively used as a food additive owing to its antioxidant and anti-inflammatory properties. Due to the sensitivity of the kidneys to noxious stimuli, they are more susceptible to various injuries. To investigate the protective mechanisms of SeMet supplementation against kidney injury, we established an in vivo experimental model using laying hens treated with SeMet (0.5 mg/kg diet) and/or lipopolysaccharide (LPS) (0.2 mg/kg. BW) and an in vitro model of chicken embryo primary kidney (CEK) cells treated with SeMet (0.075 mM) and with/ without LPS (60 μg/mL). SeMet treatment alleviated the LPS-induced kidney insufficiency and mitochondrial damage. Furthermore, it reduced the expression of TLR4, RIPK3, MLKL, DRP1, NLRP3, and IL-1β in the kidneys of laying hens. RIPK3 is known to induced necroptosis and inflammation by activating of the downstream factors DRP1 and MLKL. To investigate the mechanism whereby SeMet alleviates LPS-induced necroptosis in the kidney, we pretreated CEK cells with TLR4, RIPK3, and DRP1 inhibitors. The results demonstrated that RIPK3 inhibition resulted in a significantly increased in the mitochondrial membrane potential and downregulation of DRP1. Upon the inhibition of DRP1 expression, MLKL, NLRP3, and IL-1β expression also decreased. In summary, SeMet regulates the TLR4/RIPK3/DRP1 signaling pathway to restore the LPS-induced imbalances in mitochondrial dynamics, thereby alleviating necroptosis and inflammation in the kidneys of laying hen. Selenium also increases the expression of selenoproteins. This study provides valuable information for the development of new therapeutic strategies using SeMet to alleviate kidney injury.

Selenium participates in the formation of kidney stones by alleviating endoplasmic reticulum stress and apoptosis of renal tubular epithelial cells

ABSTRACT Objectives: To investigate the role of selenium and selenium-containing proteins in the etiology and pathogenesis of kidney stones. Methods: The HK-2 cell line was subjected to supersaturation oxalate treatment to establish an in vitro model of calcium oxalate kidney stones, while SD rats were administered with ethylene glycol to establish an in vivo model of calcium oxalate kidney stones. qPCR analysis was employed to investigate the alterations in selenoproteins within the models, and subsequently, genes exhibiting significant changes were identified. Subsequently, based on the functions of these genes, their regulatory effects on endoplasmic reticulum stress (ERS) and apoptosis during the disease progression were examined both in HK-2 cells and rat kidneys. Finally, Selenomethionine (SeMet) supplementation was introduced to explore its therapeutic potential for kidney stone management. Results: The involvement of Selenoprotein K in the pathogenesis of calcium oxalate kidney stone disease has been confirmed, exhibiting significant alterations. Manipulation of its expression levels through overexpression and knockdown techniques resulted in a corresponding reduction or increase in oxidative stress, ERS, and apoptosis within renal tubular epithelial cells. SelK regulates ERS and apoptosis by controlling the IRE1-ASK1-JNK pathway. In addition, SeMet treatment, which contains selenium, effectively reduced the levels of oxidative stress, ERS, and apoptosis in vivo and in vitro models, thereby alleviating tubular epithelial cell damage and reducing the formation of kidney stones in experimental rats. Discussion: Selenium is involved in the occurrence and development of kidney stones by regulating oxidative damage to renal tubular epithelial cells. The results suggest that dietary selenium supplementation in daily life may be of great significance for the prevention and treatment of kidney stones.

Effect of dietary supplementation of selenium-L-methionine on growth, antioxidant capacity and resistance to nitrite stress of spotted seabass (Lateolabrax maculatus) under two rearing water temperatures

A 10-week feeding trial, followed by 24-h nitrite stress, was performed to evaluate the effects of dietary selenium-L-methionine (Se-Met) on growth, Se accumulation, antioxidant capacity, transcripts of selenoproteins and histological changes of muscle as well as resistance to nitrite stress in spotted seabass (Lateolabrax maculatus) reared at optimal (27 °C) and high (33 °C) temperatures. Five experimental diets were formulated to contain 0, 0.9, 1.8, 3.5, and 7.0 mg Se-Met/kg. Each diet was fed to fish (2.60 ± 0.2 g) in two parallel treatments at 27 or 33 °C. The results showed that elevated temperature (33 °C) induced thermal stress in fish, and fish under thermal stress exhibited lower weight gain (WG) and hepatosomatic index (HSI) but a higher condition factor (CF) compared to those reared at 27 °C. However, the growth and feed utilisation were promoted in L. maculatus with 0.9 to 3.5 mg/kg Se-Met treatments. The protein and lipid content in the muscle increased with the dietary Se-Met level, and the total Se level in the whole body and muscle showed a linear increase with dietary Se-Met supplementation. Thermal stress changed the histology of the muscle, leading to raised levels of malondialdehyde (MDA), reduced antioxidant parameters in the serum and liver, and a decrease in the transcripts of selenoprotein genes in the muscle. Meanwhile, increased antioxidant capacity of serum and liver and up-regulated transcripts of selenoprotein of muscle were observed in L. maculatus reaching a maximum with 3.5 mg Se-Met/kg treatment. After 24 h of nitrite stress, thermal stress exacerbated oxidative damage caused by nitrite stress in L. maculatus. In contrast, dietary Se-Met enhanced the resistance to nitrite stress of L. maculatus fed with Se-Met enriched diets containing 0.9 to 1.8 mg Se-Met/kg. Based on the effects of dietary Se-Met on the growth, antioxidant capacity and resistance to nitrite stress of L. maculatus, this study suggests that the optimal range of Se-Met supplementation in L. maculatus diets is 1.80 to 2.39 mg Se-Met/kg of diet at 27 °C and 1.80 to 4.46 mg Se-Met/kg of diet at 33 °C.

Selenomethionine Supplementation Mitigates Liver Dysfunction, Oxidative Injury and Apoptosis through Enhancing Antioxidant Capacity and Inhibiting JNK MAPK Pathway in Piglets Fed Deoxynivalenol-Contaminated Diets.

This research evaluated the impacts of selenomethionine (Se-Met) on hepatic functions, oxidative stress, mitochondrial function, and apoptosis of piglets fed deoxynivalenol (DON)-contaminated diets. Twenty-four piglets were allocated four dietary treatments (n = 6) in a 28-day feeding trial. The four treatments included the control group, which received 0.3 mg/kg of Se (as Se-Met) without DON treatment, and the DON treatment groups received 0, 0.3, or 0.5 mg/kg Se as Se-Met. A dietary addition of 0.5 mg/kg Se improved liver pathology and reduced serum aspartate aminotransferase and lactate dehydrogenase levels in piglets fed DON-contaminated diets. Furthermore, 0.5 mg/kg Se mitigated the oxidative stress and apoptosis of piglets fed DON-contaminated diets, as indicated by the decreased reactive oxygen species level, and the down-regulated mRNA levels of NRF-1, Bax, and CASP9 in the liver. Importantly, 0.5 mg/kg Se enhanced the hepatic antioxidant capacity, as evidenced by increased hepatic total antioxidant capacity, catalase, glutathione peroxidase, and total superoxide dismutase activities, as well as the up-regulated mRNA levels of Nrf2, Gclm, NQO1, SOD1, and GPX1 in the liver. Moreover, 0.5 mg/kg Se down-regulated the p-JNK protein level in the liver of piglets fed DON-contaminated diets. Collectively, Se-Met supplementation mitigated liver dysfunction, oxidative injury, and apoptosis through enhancing antioxidant capacity and inhibiting the JNK MAPK pathway in piglets fed DON-contaminated diets.

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.

Selenomethionine protects the liver from dietary deoxynivalenol exposure via Nrf2/PPARγ-GPX4-ferroptosis pathway in mice

Deoxynivalenol (DON) is a significant Fusarium toxin that has gained global attention due to its high frequency of contamination in food and feed. It was reported to have hepatotoxicity, immunotoxicity, and reproduction toxicity in organs. On the other hand, Selenomethionine (SeMet) was proven to have anti-oxidation, tissue repairing, immunity improvement, and antifungal mycotoxin infection functions. However, the molecular mechanism by which SeMet alleviates DON damage is not yet clear. C57BL/6 mice were randomly divided into three groups, Se-A and Se-A+DON were fed with a diet containing 0.2 mg/kg Se whereas Se-S+DON were fed with a diet of 1.0 mg/kg Se. After feeding for four weeks, the mice were gavaged for 21 days with DON (2.0 mg/kg BW) or ultrapure water once per day. In the present study, we showed that SeMet significantly decreased the lipid peroxidation product malondialdehyde, and increased activities of antioxidant enzymes superoxide dismutase and total antioxidant capacity after DON exposure. In addition, our investigation revealed that SeMet regulated pathways related to lipid synthesis and metabolisms, and effectively mitigated DON-induced liver damage. Moreover, we have discovered that SeMet downregulation of N-acylethanolamine and HexCer accumulation induced hepatic lipotoxicity. Further study showed that SeMet supplementation increased protein levels of glutathione peroxidase 4 (GPX4), peroxisome proliferator-activated receptor γ (PPARγ), nuclear erythroid 2-related factor 2 (Nrf2), and upregulated target proteins, indicating suppression of oxidative stress in the liver. Meanwhile, we found that SeMet significantly reduced the DON-induced protein abundances of Bcl2, Beclin1, LC3B and proteins related to ferroptosis (Lpcat3, and Slc3a2), and downregulation of Slc7a11. In conclusion, SeMet protected the liver from damage by enhancing the Nrf2/PPARγ-GPX4-ferroptosis pathway, inhibiting lipid accumulation and hepatic lipotoxicity. The findings of this study indicated that SeMet has a positive impact on liver health by improving antioxidant capacity and relieving lipotoxicity in toxin pollution.

Effects of different levels of organic chromium and selenomethionine cocktails in broilers.

Selenium (Se) is an essential trace mineral that plays an important role in physiological processes by regulating the antioxidant defense system and enhancing immunity. Chromium is an essential mineral involved in carbohydrate and lipid metabolism and also plays a role in maintaining normal insulin function. Based on these advantages, we hypothesized that the addition of selenomethionine (SeMet) and organic chromium (OC) to broiler diets would increase Se deposition, antioxidant capacity and immune response in meat. Therefore, this study analyzed the effects of OC and SeMet on growh performance, nutrients digestibility, blood profiles, intestinal morphology, meat quality characteristics, and taxonomic analysis of broilers. A total of 168 one-day-old broiler chicken (Arbor Acres) were randomly allotted to 3 groups based on the initial body weight of 37.33 ± 0.24 g with 7 replicate per 8 birds (mixed sex). The experiments period was 28 days. Dietary treatments were folloewd: Basal diets based on corn-soybean meal (CON), basal diet supplemented with 0.2 ppm OC and 0.2 ppm SeMet (CS4), and basal diet supplemented with 0.4 ppm OC and 0.4 ppm SeMet (CS8). Supplementation of OC and SeMet did not affect on growth performance, nutrient digestibility. However, CS8 supplementation increased in duodenum villus height and villus height : crypt depth, and increased in breast meat Se deposition. In addition, CS8 group showed higher uric acid and total antioxidant status than CON group. Taxonomic analysis at phylum level revealed that Proteobacteria and Firmicutes of CS4 and CS8 were lower than CON group. In genus level, the relative abundance of fecal Lactobacillus and Enterococcus of CS4 and CS8 groups were higher than CON group. In short, 0.4 ppm OC and 0.4 ppm SeMet supplementation to broiler diet supporitng positive gut microbiome change, also enhancing antioxidant capacity, and Se deposition in breast meat.

Selenomethionine alleviates environmental heat stress induced hepatic lipid accumulation and glycogen infiltration of broilers via maintaining mitochondrial and endoplasmic reticulum homeostasis

With the increasing of global mean surface air temperature, heat stress (HS) induced by extreme high temperature has become a key factor restricting the poultry industry. Liver is the main metabolic organ of broilers, HS induces liver damage and metabolic disorders, which impairs the health of broilers and affects food safety. As an essential trace element for animals, selenium (Se) involves in the formation of antioxidant system, and its biological functions are generally mediated by selenoproteins. However, the mechanism of Se against HS induced liver damage and metabolic disorders in broilers is inadequate. Therefore, we developed the chronic heat stress (CHS) broiler model and investigated the potential protection mechanism of organic Se (selenomethionine, SeMet) on CHS induced liver damage and metabolic disorders. In present study, CHS caused liver oxidative damage, and induced hepatic lipid accumulation and glycogen infiltration of broilers, which are accompanied by mitochondrial dysfunction, abnormal mitochondrial tricarboxylic acid (TCA) cycle and endoplasmic reticulum (ER) stress. Dietary SeMet supplementation increased the hepatic Se concentration and exhibited protective effects via promoting the expression of selenotranscriptome and several key selenoproteins (GPX4, TXNRD2, SELENOK, SELENOM, SELENOS, SELENOT, GPX1, DIO1, SELENOH, SELENOU and SELENOW). These key selenoproteins synergistically improved the antioxidant capacity, and mitigated the mitochondrial dysfunction, abnormal mitochondrial TCA cycle and ER stress, thus recovered the hepatic triglyceride and glycogen concentration. What's more, SeMet supplementation suppressed lipid and glycogen biosynthesis and promoted lipid and glycogen breakdown in liver of broilers exposed to CHS though regulating the AMPK signals. Overall, our present study reveals a potential mechanism that Se alleviates environment HS induced liver damage and glycogen and lipid metabolism disorders in broilers, which provides a preventive and/or treatment measure for environment HS-dependent hepatic metabolic disorders in poultry industry.

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.

Protective effect of selenomethionine on kidney injury induced by ochratoxin A in rabbits.

The purpose of this study was to investigate the protective effect and mechanism of selenomethionine (SeMet) on ochratoxin A (OTA)-induced nephrotoxicity in rabbits. In total, sixty Ira rabbits were randomly divided into 5 groups (the control group, OTA group, 0. 2mg/kg SeMet + OTA group, 0. 4mg/kg SeMet + OTA group, and 0. 6mg/kg SeMet + OTA group). The rabbits were fed diets supplemented with different doses of SeMet for 21days and given 0. 2mg/kg OTA starting on day 15 for a week. The results showed that the SeMet supplementation could improve the changes in blood physiological indices and renal function decline caused by OTA poisoning, and alleviate pathological kidney injury in the rabbits. SeMet also increased the activities of total antioxidant capacity, superoxide dismutase, and glutathione peroxidase, and decreased the contents of malondialdehyde and reactive oxygen species and the expression of interleukin-1β, interleukin-6, and tumor necrosis factor-α in the damaged kidneys of the rabbits. In addition, the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream gene heme oxygenase 1 (HO-1) was also inhibited after OTA poisoning, while SeMet activated the Nrf2 signaling pathway and enhanced the expression of Nrf2 and the downstream gene HO-1. In conclusion, SeMet protected against kidney injury caused by OTA in rabbits, and the mechanism may be the activation of the Nrf2 signaling pathway.

Selenomethionine incorporation in proteins of individual mammalian cells determined with a genetically encoded fluorescent sensor

Selenomethionine (SeMet) randomly replaces methionine (Met) in protein translation. Because of strongly differing redox properties of SeMet and Met, SeMet mis-incorporation may have detrimental effects on protein function, possibly compromising the use of nutritional SeMet supplementation as an anti-oxidant. Studying the functional impact of SeMet in proteins on a cellular level is hampered by the lack of accurate and efficient methods for estimating the SeMet incorporation level in individual viable cells. Here we introduce and apply a method to measure the extent of SeMet incorporation in cellular proteins by utilizing a genetically encoded fluorescent methionine oxidation probe. Supplementation of SeMet in mammalian culture medium resulted in >84% incorporation of SeMet, and SeMet labeling as low as 5% was readily measured. Kinetics and extent of SeMet incorporation on the single-cell level under live-cell imaging conditions provided direct access to protein turn-over kinetics and SeMet redox properties in a cellular context. The method is furthermore suited for experiments utilizing high-throughput fluorescence microplate readers or fluorescence-activated cell sorting (FACS) analysis.

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.

Selenomethionine modulates insulin secretion in the MIN6-K8 mouse insulinoma cell line.

Selenium is an essential trace element of interest for its potential role in glucose homeostasis. The present study investigated the impact of selenium supplementation as selenomethionine (SeMet) on insulin secretion in MIN6-K8 cells, a pancreatic β-cell model. We found that SeMet enhanced percent glucose-induced insulin secretion, while also increasing tolbutamide- and KCl-induced percent insulin secretion. RNA-sequencing showed that SeMet supplementation altered expression of several selenoproteins, including glutathione peroxidase 3 (Gpx3) and selenoprotein P (SelP). Targeted knockdown of Gpx3 increased both percent and total insulin release, while SelP knockdown increased insulin content and insulin release. Collectively, these studies support a putative role for selenium and selenoproteins in the regulation of insulin secretion, glucose homeostasis, and diabetes risk.

Selenomethionine alleviated Ochratoxin A induced pyroptosis and renal fibrotic factors expressions in MDCK cells.

Ochratoxin A (OTA) is universally known to induce nephrotoxicity via inducing oxidative stress and apoptosis, inhibiting protein synthesis and activating autophagy. Our previous studieshave proved that OTA induces nephrotoxicity in vitro and in vivo by adjusting the NOD-like receptor protein 3 (NLRP3) inflammasome activation and caspase-1-dependent pyroptosis. Based on these findings, we further investigated the protective role of selenomethionine (SeMet) on OTA-caused nephrotoxicity using the Madin-Darby canine kidney (MDCK) epithelial cells as anin vitro model, proposing to offer a new way for remedyingOTA-induced nephrotoxicity by nutritional manipulation. We measured the cell vitality, lactate dehydrogenase (LDH) activity and the expression of renal fibrotic genes, NLRP3 inflammasome and pyroptosis related genes. MTT and LDH results indicated that SeMet supplementation significantly mitigated 2.0 μg/ml OTA-induced cytotoxicity in MDCK cells (p < 0.05). Meanwhile, SeMet alleviated OTA induced increase of reactive oxygen species in MDCK cells. Then, the expressions of α-SMA, Vimentin, and TGF-β were detected both in mRNA and protein levels. The results indicated 8 μM SeMet supplementation could significantly downregulate the expression of OTA-induced renal fibrosis-related genes (p < 0.05). In addition, the upregulation of OTA-induced NLRP3 inflammasome and pyroptosis downstream genes was also significantly inhibited by 8 μM of SeMet (p < 0.05). In summary, SeMet could alleviate OTA-induced renal fibrotic genes expression and reduce NLRP3-caspase-1-dependent pyroptosis. Therefore, SeMet supplementation may become an effective approach for preserving animals from renal injury exposed to OTA.

Selenium-enriched Polysaccharide: an Effective and Safe Selenium Source of C57 Mice to Improve Growth Performance, Regulate Selenium Deposition, and Promote Antioxidant Capacity.

Selenium-enriched polysaccharide (SeEPS) was prepared by reducing Se(IV) to elemental selenium and organic selenium in polysaccharide medium by the obtained Enterobacter cloacae strain Z0206 under aerobic conditions. In the present study, we focused on investigating the role of short-term supplementation of SeEPS at supernutritional doses in the regulation of growth performance, liver damage, antioxidant capacity, and selenium (Se) accumulation in C57 mice. Thirty-two C57 mice were randomly divided into four groups: the control group was gavaged with equal volume of phosphate-buffered saline, while the sodium selenite (Na2SeO3), selenomethionine (SeMet), and SeEPS groups were gavaged with 0.5mg Se/kg BW of Na2SeO3, SeMet, and selenium-enriched polysaccharide (n = 8), respectively. We examined liver injury indicators, antioxidant capacity in the serum and liver, selenium deposition at different sites, selenoprotein levels, and selenocysteine-synthesizing and degradation-associated gene expression in mouse livers. SeEPS supplementation dramatically increased average daily weight gain but reduced the feed-to-gain ratio (F/G) of mice (P < 0.05). Compared to Na2SeO3 and SeMet supplementation, SeEPS supplementation at supernutritional doses did not cause the liver damage. SeEPS supplementation also markedly enhanced total antioxidant capacity (T-AOC), catalase (CAT), glutathione peroxidase (GSH-PX), and total superoxide dismutase (T-SOD) activities but reduced malondialdehyde (MDA) levels in the liver and serum (P < 0.05), while significantly increasing selenocysteine-synthesizing and degradation-related gene (SEPHS2, SEPSECS, Secisbp, Scly) expression at the mRNA level (P < 0.05), thus upregulating the mRNA levels of selenoproteins (SELENOP, SELENOK) (P < 0.05). We suggest that SeEPS could be a potential replacement for inorganic selenium to improve animals' growth performance, promote antioxidant capacity, and regulate selenium deposition.

Assessment of the mercury-selenium antagonism in rainbow trout fish

This study aims at the assessment of mercury (Hg)-selenium (Se) antagonism in fish. For this purpose, rainbow trout fish (Oncorhynchus mykiss) were exposed to methylmercury (MeHg) under controlled conditions, in the presence or absence of selenomethionine (SeMet) using an in-house prepared diet (enriched with MeHg and SeMet at 0.2 μg/g and 5.0 μg/g, respectively). The total duration of the exposure study was 3 months. Fish was sampled and analysed for total Se (SeT) and total mercury (HgT) content after 1, 2 and 3 months of exposure. Six feeding protocols were compared, depending on the exposure type: (i) no MeHg nor SeMet exposure (control group); (ii) exposure to SeMet solely; (iii) exposure to MeHg solely; (iv) exposure to both MeHg and SeMet; (v) exposure first to MeHg during 1 month and then to SeMet during 2 months and (vi), exposure to SeMet during 1 month and then to MeHg for 2 months. The levels of SeT and HgT in the fish (control and supplemented with MeHg/SeMet) were measured by inductively coupled plasma-mass spectrometry (ICPMS).Steadily (linear) bioaccumulation of MeHg in the fish muscle occurred when the fish were exposed individually to this species during the period. The bioaccumulation of MeHg is diminished when the fish are firstly exposed to SeMet and then to MeHg, hence indicating the MeHg detoxification due to SeMet supplementation.

Selenium Kinetics in Humans Change Following 2 Years of Supplementation With Selenomethionine.

BackgroundSelenium (Se) is a nutritionally essential trace element and health may be improved by increased Se intake. Previous kinetic studies have shown differences in metabolism of organic vs. inorganic forms of Se [e.g., higher absorption of selenomethionine (SeMet) than selenite (Sel), and more recycling of Se from SeMet than Sel]. However, the effects on Se metabolism after prolonged Se supplementation are not known.ObjectiveTo determine how the metabolism and transport of Se changes in the whole-body in response to Se-supplementation by measuring Se kinetics before and after 2 years of Se supplementation with SeMet.MethodsWe compared Se kinetics in humans [n = 31, aged 40 ± 3 y (mean ± SEM)] studied twice after oral tracer administration; initially (PK1), then after supplementation for 2 y with 200 µg/d of Se as selenomethionine (SeMet) (PK2). On each occasion, we administered two stable isotope tracers of Se orally: SeMet, the predominant food form, and selenite (Na2 76SeO3, or Sel), an inorganic form. Plasma and RBC were sampled for 4 mo; urine and feces were collected for the initial 12 d of each period. Samples were analyzed for tracers and total Se by isotope dilution GC-MS. Data were analyzed using a compartmental model, we published previously, to estimate fractional transfer between pools and pool masses in PK2.ResultsWe report that fractional absorption of SeMet or Sel do not change with SeMet supplementation and the amount of Se absorbed increased. The amount of Se excreted in urine increases but does not account for all the Se absorbed. As a result, there is a net incorporation of SeMet into various body pools. Nine of the 11 plasma pools doubled in PK2; two did not change. Differences in metabolism were observed for SeMet and Sel; RBC uptake increased 247% for SeMet, urinary excretion increased from two plasma pools for Sel and from two different pools for SeMet, and recycling to liver/tissues increased from one plasma pool for Sel and from two others for SeMet. One plasma pool increased more in males than females in PK2.ConclusionsOf 11 Se pools identified kinetically in human plasma, two did not increase in size after SeMet supplementation. These pools may be regulated and important during low Se intake.

Selenium alleviates the negative effect of heat stress on myogenic differentiation of C2C12 cells with the response of selenogenome

With the globe warming, heat stress (HS) has frequently affected animal production. Selenium (Se) is an essential trace element for animals and exerts most of its biological functions through selenoproteins. We previously demonstrated that the damage to C2C12 cells by HS accompanied with the response of selenoprotein encoding genes and proteins. The objective of this study was to investigate whether selenium supplementation (sodium selenite, SS and selenomethionine, SeMet) could alleviate the negative effect of heat stress on the differentiation of C2C12 cells, and interpret the potential corresponding selenoproteins response. The differentiated cells were cultured for 4 and 8 days under different condition: at 37 °C, 41.5 °C and 41.5 °C with 0.5 μmol Se/L SS or SeMet, and the HSP70, cell apoptosis, selenoproteins and cell differentiation-related gene or protein were detected. The result showed that HS up-regulated (P < 0.05) mRNA and protein levels of HSP70 and gene expression of AMPKα1 and AMPKα2, and down-regulated (P < 0.05) mRNA or protein levels of MYOGENIN and MYOD. Meanwhile, up to 15 and 17 selenoprotein genes expression were significantly changed response to 4-and 8-days HS challenge, respectively. Relative to the HS group, SS and SeMet supplementation down-regulated the mRNA and protein abundance of HSP70 to different degrees, and partly recovered (P < 0.05) the mRNA or protein abundance of MYOGENIN and MYOD at 4th and 8th day. Especially, 16 and 10 selenoprotein genes expression in cells affected by HS were altered by SS and SeMet supplementation, respectively. Both SS and SeMet supplementation modestly increased (P < 0.05) protein levels of GPX1 and SELENON in cells under HS. In summary, Se supplementation partly alleviated the negative impact of HS on myogenic differentiation of C2C12 cells and the process may associate with the alternation of selenoprotein expression pattern, and SeMet exhibits better effect than SS.

Targeted Metabolomics Analysis Reveals that Dietary Supranutritional Selenium Regulates Sugar and Acylcarnitine Metabolism Homeostasis in Pig Liver

The association between high selenium (Se) intake and metabolic disorders such as type 2 diabetes has raised great concern, but the underlying mechanism remains unclear. Through targeted metabolomics analysis, we examined the liver sugar and acylcarnitine metabolism responses to supranutritional selenomethionine (SeMet) supplementation in pigs. Thirty-six castrated male pigs (Duroc-Landrace-Yorkshire, 62.0±3.3kg) were fed SeMet adequate (Se-A, 0.25mg Se/kg) or SeMet supranutritional (Se-S, 2.5mg Se/kg) diets for 60 d. The Se concentration, biochemical, gene expression, enzyme activity, and energy-targeted metabolite profiles were analyzed. The Se-S group had greater fasting serum concentrations of glucose (1.9-fold), insulin (1.4-fold), and free fatty acids (FFAs,1.3-fold) relative to the Se-A group (P <0.05). The liver total Se concentration was 4.2-fold that of the Se-A group in the Se-S group (P <0.05), but expression of most selenoprotein genes and selenoenzyme activity did not differ between the 2 groups. Seven of 27 targeted sugar metabolites and 4 of 21 acylcarnitine metabolites significantly changed in response to high SeMet (P <0.05). High SeMet supplementation significantly upregulated phosphoenolpyruvate carboxy kinase (PEPCK) activity by 64.4% and decreased hexokinase and succinate dehydrogenase (SDH) activity by 46.5-56.7% (P <0.05). The relative contents of glucose, dihydroxyacetone phosphate, α-ketoglutarate, fumarate, malate, erythrose-4-phosphate, and sedoheptulose-7-phosphate in the Se-S group were 21.1-360% greater than those in the Se-A group (P <0.05). The expression of fatty acid synthase (FASN) and the relative contents of carnitine, hexanoyl-carnitine, decanoyl-carnitine, and tetradecanoyl-carnitine in the Se-S group were 35-97% higher than those in the Se-A group (P <0.05). Dietary high SeMet-induced hyperglycemia and hyperinsulinemia were associated with suppression of sugar metabolism and elevation of lipid synthesis in pig livers. Our research provides novel insights into high SeMet intake-induced type 2 diabetes.