Se-methylselenocysteine ameliorates mitochondrial function by targeting both mitophagy and autophagy in the mouse model of Alzheimer's disease.

Background: Alzheimer's disease (AD) exerts tremendous pressure on families and society due to its unknown etiology and lack of effective treatment options. Our previous study had shown that Se-methylselenocysteine (SMC) improved the cognition and synaptic plasticity of triple-transgenic AD (3 × Tg-AD) mice and alleviated the related pathological indicators. We are dedicated to investigating the therapeutic effects and molecular mechanisms of SMC on mitochondrial function in 3 × Tg-AD mice. Methods: Transmission electron microscopy (TEM), western blotting (WB), mitochondrial membrane potential (ΔΨm), mitochondrial swelling test, and mitochondrial oxygen consumption test were used to evaluate the mitochondrial morphology and function. Mitophagy flux and autophagy flux were assessed with immunofluorescence, TEM and WB. The Morris water maze test was applied to detect the behavioral ability of mice. Results: The destroyed mitochondrial morphology and function were repaired by SMC through ameliorating mitochondrial energy metabolism, mitochondrial biogenesis and mitochondrial fusion/fission balance in 3 × Tg-AD mice. In addition, SMC ameliorated mitochondria by activating mitophagy flux via the BNIP3/NIX pathway and triggering autophagy flux by suppressing the Ras/Raf/MEK/ERK/mTOR pathway. SMC remarkably increased the cognitive ability of AD mice. Conclusions: This research indicated that SMC might exert its therapeutic effect by protecting mitochondria in 3 × Tg-AD mice.

Effect of Dietary Methylseleninic Acid and Se-Methylselenocysteine on Carcinogen-Induced, Androgen-Promoted Prostate Carcinogenesis in Rats.

Selenomethionine (SeMet) did not prevent prostate cancer in the SELECT trial and in two hormone-driven rat models. However, we have shown that daily oral bolus administration of next-generation selenium forms, methylseleninic acid (MSeA) and Se-methylselenocysteine (MSeC) at 3 mg Se/kg body weight, inhibits prostate carcinogenesis in the TRAMP and pten-deficient mouse models and In Vivo growth of human prostate cancer cells. Here, we determined whether these Se forms prevent prostate cancer in a chemically induced-androgen promoted carcinogenesis rat model in which SeMet was not preventive. WU rats were treated with methylnitrosourea, and one week later, slow-release testosterone implants when they were randomized to groups fed AIN-93M diet supplemented with 3 ppm selenium as MSeA or MSeC or control diet. Mean survival, tumor incidence in all accessory sex glands combined (dorsolateral and anterior prostate plus seminal vesicle) and the incidence of tumors confined to dorsolateral and/or anterior prostate were not statistically significantly different among the groups. Thus, MSeA and MSeC feeding was not preventive in this model. The contrast with the inhibitory effects of MSeA and MSeC in mouse models may be due to differences in carcinogenic mechanisms, selenium dosage, delivery mode, and pharmacokinetics or fundamental rat-mouse differences in selenium metabolism.

Implication of methylselenocysteine in combination chemotherapy with gemcitabine for improved anticancer efficacy.

The limitations associated with cancer monotherapy including dose dependent toxicity and drug resistance can be addressed by combination chemotherapy. The combination of antineoplastic agents improves the cytotoxic activity in comparison to the single-agent based therapy in a synergistic or an additive mode by reducing tumor growth as well as metastatic ability. In the present investigation, we explored the potential of methylselenocysteine (MSC) in combination chemotherapy with gemcitabine (GEM). The cytotoxic activity of GEM and MSC was determined in various cell lines and based on the activity, A549 cells were explored for the mechanistic studies including DAPI staining, measurement of oxidative stress, mitochondrial membrane potential loss, nitric oxide level, western blotting, cell migration and colony formation assays. A549 cells in combination treatment with MSC and GEM demonstrated enhanced cytotoxicity with more irregular cellular morphology as well as chromatin condensation and nuclear blebbing. The selected combination also significantly triggered ROS generation and mitochondrial destabilization, and alleviated cell migration potential and clonogenic propensity of A549 cells. Also, caspase-3 and PARP mediated apoptosis was observed in the combination treated cells. MSC based drug combination could offer the attributes of improved drug delivery and there was a 6-folds dose reduction of GEM in combination. Further, antitumor study in Ehrlich solid tumor model showed the efficacy of MSC combination with GEM for the enhanced antitumor activity. The proposed combination demonstrated the potential for further translational studies.

L-Se-methylselenocysteine loaded mucoadhesive thermogel for effective treatment of Vulvar candidiasis.

Vulvar candidiasis (VVC) is a vaginitis caused by vaginal mucosa infection of Candida, which greatly impairs women's health. Although there are more and more thiazoles on the market, new classes of antifungal drugs are still missing, it is still challenging to treat azole-resistant candidal vaginitis. We found that L-Se-methylselenocysteine (L-SeMC) could effectively inhibit the growth of Candida albicans, reduce the density and length of the mycelia. To extend the retention time of L-SeMC in the vaginal tract and enhance its therapeutic effect for VVC, a mucoadhesive thermogel (NAC-HA thermogel) was successfully synthesized and prepared. The gelation window was around 29-56 °C for L-SeMC loaded mucoadhesive thermogel (L-SeMC@NAC-HA thermogel), which exhibited a sustained release profile in the in vitro release study and an extended retention time in the vaginal tract. Besides, L-SeMC@NAC-HA thermogel exhibited a good safety profile in the in vivo safety study. The in vivo anti-VVC effect was examined in a rat VVC model and L-SeMC@NAC-HA thermogel significantly reduced the number of Candida albicans in the vaginal secreta, mitigated the vaginal damage and reduced the secretion of proinflammatory factors (TNF-α, IL-1α and IL-ß). Therefore, it is a promising therapy for the clinical treatment of VVC in the near future.

Methylselenocysteine Potentiates Etoposide-Induced Cytotoxicity by Enhancing Gap Junction Activity.

Homomeric or heteromeric connexin (Cx) hemichannels-composed gap junction (GJ) intercellular channel can mediate direct cell-to-cell communication. Accumulating studies indicate that GJs potentiate the cytotoxicity of antitumor drugs in malignant cells. Methylselenocysteine (MSC), a selenium compound from garlic, has been reported to modulate the activity of antineoplastic drugs, but the underlying mechanism remains unclear. This study investigates the efficacy of MSC on chemotherapeutic drugs-induced cytotoxicity and the relationship between this effect and the regulation of GJ function by MSC. Firstly, a doxycycline-regulated HeLa cell line expressing heteromeric Cx26/Cx32 was used as a tool. Etoposide, but not cisplatin or 5-fluorouracil, showed remarkable cytotoxicity in high-density (with GJ formation) cultures than in low-density (without GJ formation) in transformed HeLa cells. And cell density had no effect on etoposide-mediated cytotoxicity in the absence of Cx expression. MSC substantially enhanced etoposide-induced cytotoxicity, and this effect was only detected in the presence of functional GJs. Subsequently, MSC potentiated structural Cx expression as evidenced by increased dye coupling, but no alteration in Cx mRNA expression level in either transformed or primary cancer cell lines. Finally, a redox mechanism involving glutathione (GSH) was found to be related to the posttranscriptional modulation of Cx expression by MSC in HeLa cells. In conclusion, we provide the novel finding that MSC increases etoposide-mediated cytotoxicity by enhancing GJ activity, due to elevated Cx expression through a GSH-dependent posttranscriptional mechanism. More generally, the study highlights potential benefit of the combination of GJ modulators and chemotherapeutic agents in anticancer treatment.

Application of alpha-methyl selenocysteine as a tool for the study of selenoproteins.

Selenocysteine (Sec) is the 21st proteogenic amino acid and it is now widely accepted that Sec is involved in redox biochemistry when incorporated in proteins. However, many of the chemical mechanisms for Sec bioactivity remain unknown. Herein, we describe a derivative of Sec, alpha-methyl Sec ((αMe)Sec), that is a useful chemical tool to study selenoenzyme mechanisms. (αMe)Sec is identical to Sec except the Cα-H is replaced with a Cα-methyl group, which prevents this derivative from undergoing oxygen-mediated ß-syn elimination to dehydroalanine, which is a common problem with Sec-containing peptides and proteins. Thus, since (αMe)Sec-containing peptides and proteins cannot lose the side-chain selenium atom when oxidized, mechanistic studies can be performed that are not always possible with Sec. In this chapter, we provide detailed methods for the incorporation of (αMe)Sec into peptides using solid phase peptide synthesis and subsequent incorporation into mammalian thioredoxin reductase using protein semisynthesis. We then provide two examples of how (αMe)Sec has been used as a chemical tool to study selenoenzyme mechanism. Finally, we discuss future applications where we envision (αMe)Sec will be useful.

Immunomodulatory and Anti-Inflammatory Properties of Selenium-Containing Agents: Their Role in the Regulation of Defense Mechanisms against COVID-19.

The review presents the latest data on the role of selenium-containing agents in the regulation of diseases of the immune system. We mainly considered the contributions of selenium-containing compounds such as sodium selenite, methylseleninic acid, selenomethionine, and methylselenocysteine, as well as selenoproteins and selenium nanoparticles in the regulation of defense mechanisms against various viral infections, including coronavirus infection (COVID-19). A complete description of the available data for each of the above selenium compounds and the mechanisms underlying the regulation of immune processes with the active participation of these selenium agents, as well as their therapeutic and pharmacological potential, is presented. The main purpose of this review is to systematize the available information, supplemented by data obtained in our laboratory, on the important role of selenium compounds in all of these processes. In addition, the presented information makes it possible to understand the key differences in the mechanisms of action of these compounds, depending on their chemical and physical properties, which is important for obtaining a holistic picture and prospects for creating drugs based on them.

In vitro cytotoxic data on Se-methylselenocysteine conjugated to dendritic poly(glycerol) against human squamous carcinoma cells.

Polymeric nanoparticles acting as sources of selenium (Se) are currently an interesting topic in cancer chemotherapy. In this study, polyglycerol dendrimer (DPGLy) was functionalized with seleno-methyl-selenocysteine (SeMeCys) by means of Steglich esterification with 4-dimethylaminopyridine/(l-ethyl-3-(3-dimethylaminopropyl)carbodiimide) (EDC/DMAP) and cerium chloride as cocatalyst in acetonitrile at quantitative yields of 98 ± 1%. The SeMeCys coupling DPGLy efficiency vs. time were determined by Fourier Transform infrared spectroscopy (FTIR) and ultraviolet-visible (UV-Vis) spectroscopy. The cytotoxic effects of SeMeCys-DPGLy on the Chinese Hamster ovary cell line (CHO-K1) and head and neck squamous cell carcinoma (HNSCC) cells line were assessed by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. No signs of general toxicity of SeMeCys-DPGLy against CHO-K1 cells were detectable at which cell viability was greater than 98%. MTS assays revealed that SeMeCys-DPGLy reduced HNSCC cell viability and proliferation at higher doses and long incubation times.

Sex-dimorphic distribution and anti-oxidative effects of selenomethionine and Se-methylselenocysteine supplementation.

Selenium (Se) is a vital trace element in human beings and is essential for protection against oxidative stress. This study aimed to investigate the accumulation and antioxidant effects of two organic seleniums, L-selenomethionine (SM) and L-Se-methylselenocysteine (SMC), through in vivo and in vitro experiments. L02 cells were pretreated with 10 nM SM or SMC for 24 h, followed by exposure to 100 nM of H2O2. Cell viability, apoptosis, and antioxidant capacity were detected to evaluate SM and SMC's protective effect. Organic selenium (SM and SMC) and inorganic selenium (sodium selenite, SS) were compared in terms of their in vivo accumulation and antioxidant capacity when supplemented daily and subsequently deprived in SD rats. Our results show that SM or SMC pre-treatment could significantly prevent elevated apoptosis and declined antioxidant ability. We found that organic Se supplementation resulted in higher Se accumulation than inorganic Se in the liver and kidney. The antioxidant capacity of liver and kidney tissues from rats fed with either organic selenium was significantly improved and was higher than that of SS. In summary, this study suggests that organic selenium supplements are more effective in facilitating Se accumulation in liver and kidney, enhancing antioxidant capacities, thereby protecting cells from oxidative stress. PRACTICAL APPLICATION: This study compared the antioxidant capacity of sodium selenite, L-selenomethionine, and L-Se-methylselenocysteine in vitro and in vivo. The results showed that organic selenium has a stronger antioxidant capacity and that significant differences exist in its absorption and conversion in male and female rats. Our results provide theoretical guidance for dietary supplementation of selenium.

Se-Methylselenocysteine Alleviates Liver Injury in Diethylnitrosamine (DEN)-Induced Hepatocellular Carcinoma Rat Model by Reducing Liver Enzymes, Inhibiting Angiogenesis, and Suppressing Nitric Oxide (NO)/Nitric Oxide Synthase (NOS) Signaling Pathway.

BACKGROUND Hepatocellular carcinoma is the third leading cause of cancer-associated mortality. This study aimed to investigate the effects of se-methylselenocysteine (MSC) on oncogenesis of diethylnitrosamine (DEN)-induced hepatocellular carcinoma. MATERIAL AND METHODS A hepatocellular carcinoma rat model was established by administering DEN. Rat models were divided into Model (0.1 mg/kg MSC), Model+0.3 mg/kg MSC, Model+1 mg/kg MSC, and Model+3 mg/kg MSC groups. A Normal control group consisted of mice not administered MSC. Hematoxylin and eosin staining was used to determine liver injury. Immunohistochemical analysis was conducted to identify CD34 and vascular endothelial growth factor (VEGF) expression. VEGF gene transcription was detected with RT-PCR. Biochemical analyses were performed to determine alanine aminotransferase, aspartate aminotransferase, total bilirubin, γ-glutamyl transpeptidase, alkaline phosphatase, and albumin levels in serum, and nitric oxide (NO)/nitric oxide synthase (NOS) levels in liver tissues. Transmission electron microscopy was used to observe the ultra-microstructures of hepatocytes. RESULTS MSC treatment markedly alleviated liver injury and nuclear lesions in the treatment groups compared to the Model group. MSC treatment significantly improved liver functions in the treatment groups compared to the Model group (P<0.05). MSC treatment significantly decreased CD34 expression and NO and NOS levels in liver tissues and suppressed VEGF expression compared to the Model group (all P<0.05). CONCLUSIONS MSC administration alleviated liver injury in a DEN-induced hepatocellular carcinoma rat model through reducing liver enzymes, inhibiting angiogenesis, and suppressing the NO/NOS signaling pathway.

L-Se-methylselenocysteine sensitizes lung carcinoma to chemotherapy.

OBJECTIVES: Organic Selenium (Se) compounds such as L-Se-methylselenocysteine (L-SeMC/SeMC) have been employed as a class of anti-oxidant to protect normal tissues and organs from chemotherapy-induced systemic toxicity. However, their comprehensive effects on cancer cell proliferation and tumour progression remain elusive. MATERIALS AND METHODS: CCK-8 assays were conducted to determine the viabilities of cancer cells after exposure to SeMC, chemotherapeutics or combined treatment. Intracellular reactive oxygen species (ROS) levels and lipid peroxidation levels were assessed via fluorescence staining. The efficacy of free drugs or drug-loaded hydrogel against tumour growth was evaluated in a xenograft mouse model. RESULTS: Among tested cancer cells and normal cells, the A549 lung adenocarcinoma cells showed higher sensitivity to SeMC exposure. In addition, combined treatments with several types of chemotherapeutics induced synergistic lethality. SeMC promoted lipid peroxidation in A549 cells and thereby increased ROS generation. Significantly, the in vivo efficacy of combination therapy was largely potentiated by hydrogel-mediate drug delivery. CONCLUSIONS: Our study reveals the selectivity of SeMC in the inhibition of cancer cell proliferation and develops an efficient strategy for local combination therapy.

Se-Methylselenocysteine (SMC) Improves Cognitive Deficits by Attenuating Synaptic and Metabolic Abnormalities in Alzheimer's Mice Model: A Proteomic Study.

Se-methylselenocysteine (SMC) is a major selenocompound in selenium (Se) enriched plants and has been found to ameliorate neuropathology and cognitive deficits in triple-transgenic mice model of Alzheimer's disease (3 × Tg-AD mice). To explore the underlying molecular mechanisms, the present study is designed to elucidate the protein changes in the cortex of SMC-treated 3 × Tg-AD mice. After SMC supplementation, proteomic analysis revealed that 181, 271, and 41 proteins were identified as differentially expressed proteins (DEPs) between 3 × Tg-AD mice vs wild type (AD/WT group), SMC-treated AD mice vs AD (AD + SMC/AD), and AD + SMC/WT group, respectively. Among these, 138 proteins in the diseased group were reversed by SMC treatment. The DEPs in AD/WT group and AD + SMC/AD group were mainly related to metabolism, synapses, and antioxidant proteins, while their levels were decreased in AD mice but up-regulated after treating with SMC. In addition, we found reduced ATP levels and destroyed synaptic structures in the AD mice brains, which were significantly ameliorated upon SMC treatment. Our study suggests that energy metabolism disorders, abnormal amino acid metabolism, synaptic dysfunction, and oxidative stress may be the key pathogenic phenomena of AD. SMC reversed the expression of proteins associated with them, which might be the main mechanism of its intervention in AD.

Suppression of lipopolysaccharide-induced activation of RAW 264.7 macrophages by Se-methylseleno-l-cysteine.

Se-methylseleno-l-cysteine (l-SeMC) is a natural source of organic selenium for humans. Although it has a structure similar to that of l-Cysteine (l-Cys), its anti-inflammatory properties and possible underlying mechanisms have not been explored. Here, we compared the anti-inflammatory activities of inorganic selenium (selenite), l-Cys, and l-SeMC in lipopolysaccharide (LPS)-activated RAW 264.7 murine macrophages and focused on the related molecular and biochemical events. The results showed that, anti-inflammatory activity of l-SeMC was much stronger compared to both individual l-Cys treatment and l-Cys/selenite combinations. The organic form of selenium may play a crucial role in the effects of l-SeMC. Further study confirmed that l-SeMC suppressed the RNA expression of iNOS, TNF-α, IL-1ß, IL-6, COX-2, and MMP-9, as well as the release of NO, TNF-α, IL-6, IL-12p70, COX-2, and PGE2 from LPS-activated RAW264.7 macrophages in a concentration-dependent manner. Moreover, l-SeMC prevented LPS-induced changes in cell morphology. l-SeMC concentrations between 50 and 200 µM exhibited an anti-inflammatory effect closed to that exhibited by 20 µM dexamethasone. Our results demonstrated that l-SeMC effectively inhibited the activation of RAW 264.7 macrophages induced by LPS, and suggested that l-SeMC could be a potential functional food component for the prevention or treatment of inflammatory diseases.

Can Selenoenzymes Resist Electrophilic Modification? Evidence from Thioredoxin Reductase and a Mutant Containing α-Methylselenocysteine.

Selenocysteine (Sec) is the 21st proteogenic amino acid in the genetic code. Incorporation of Sec into proteins is a complex and bioenergetically costly process that evokes the following question: "Why did nature choose selenium?" An answer that has emerged over the past decade is that Sec confers resistance to irreversible oxidative inactivation by reactive oxygen species. Here, we explore the question of whether this concept can be broadened to include resistance to reactive electrophilic species (RES) because oxygen and related compounds are merely a subset of RES. To test this hypothesis, we inactivated mammalian thioredoxin reductase (Sec-TrxR), a mutant containing α-methylselenocysteine [(αMe)Sec-TrxR], and a cysteine ortholog TrxR (Cys-TrxR) with various electrophiles, including acrolein, 4-hydroxynonenal, and curcumin. Our results show that the acrolein-inactivated Sec-TrxR and the (αMe)Sec-TrxR mutant could regain 25% and 30% activity, respectively, when incubated with 2 mM H2O2 and 5 mM imidazole. In contrast, Cys-TrxR did not regain activity under the same conditions. We posit that Sec enzymes can undergo a repair process via ß-syn selenoxide elimination that ejects the electrophile, leaving the enzyme in the oxidized selenosulfide state. (αMe)Sec-TrxR was created by incorporating the non-natural amino acid (αMe)Sec into TrxR by semisynthesis and allowed for rigorous testing of our hypothesis. This Sec derivative enables higher resistance to both oxidative and electrophilic inactivation because it lacks a backbone Cα-H, which prevents loss of selenium through the formation of dehydroalanine. This is the first time this unique amino acid has been incorporated into an enzyme and is an example of state-of-the-art protein engineering.

The Effect of Methylselenocysteine and Sodium Selenite Treatment on microRNA Expression in Liver Cancer Cell Lines.

The unique character of selenium compounds, including sodium selenite and Se-methylselenocysteine (MSC), is that they exert cytotoxic effects on neoplastic cells, providing a great potential for treating cancer cells being highly resistant to cytostatic drugs. However, selenium treatment may affect microRNA (miRNA) expression as the pattern of circulating miRNAs changed in a placebo-controlled selenium supplement study. This necessitates exploring possible changes in the expression profiles of miRNAs. For this, miRNAs being critical for liver function were selected and their expression was measured in hepatocellular carcinoma (HLE and HLF) and cholangiocarcinoma cell lines (TFK-1 and HuH-28) using individual TaqMan MicroRNA Assays following selenite or MSC treatments. For establishing tolerable concentrations, IC50 values were determined by performing SRB proliferation assays. The results revealed much lower IC50 values for selenite (from 2.7 to 11.3 µM) compared to MSC (from 79.5 to 322.6 µM). The treatments resulted in cell line-dependent miRNA expression patterns, with all miRNAs found to show fold change differences; however, only a few of these changes were statistically different in treated cells compared to untreated cells below IC50. Namely, miR-199a in HLF, miR-143 in TFK-1 upon MSC treatment, miR-210 in HLF and TFK-1, miR-22, -24, -122, -143 in HLF upon selenite treatment. Fold change differences revealed that miR-122 with both selenium compounds, miR-199a with MSC and miR-22 with selenite were affected. The miRNAs showing minimal alterations included miR-125b and miR-194. In conclusion, our results revealed moderately altered miRNA expression in the cell lines (less alterations following MSC treatment), being miR-122, -199a the most affected and miR-125b, -194 the least altered miRNAs upon selenium treatment.

Selenium biofortification in Hericium erinaceus (Lion's Mane mushroom) and its in vitro bioaccessibility.

Hericium erinaceus is a traditional edible mushroom. Selenium (Se) is an essential trace element for humans and other mammals. To develop a Se biofortification strategy for H. erinaceus, the effects of selenate, selenite, and selenomethionine (SeMet) on Se uptake and mushroom growth were investigated. Selenium bioaccessibility and the major Se species present in Se-enriched H. erinaceus were tested in vitro . The H. erinaceus growth was efficiently affected by SeMet than by selenite and selenate. Selenium concentrations in fruiting bodies increased with substrate Se concentration and disturbed accumulation of other microelements. Substrate Se was absorbed and transformed into organic forms. The major Se species in Se-enriched fruiting bodies was SeMet (>63.9%). During in vitro gastrointestinal digestion tests, 51% of total Se was released, and selenocystine (SeCys2 ) (90%) and Se-methylselenocysteine (MeSeCys) (76%) were more easily digested than SeMet (51%). H. erinaceus is suggested as a novel dietary source of supplemental bioavailable Se.

Green and simple extraction of free seleno-amino acids from powdered and lyophilized milk samples with natural deep eutectic solvents.

Natural deep eutectic solvents (NADES) were introduced for the extraction of free seleno-amino acids from lyophilized and powdered milk samples. Different NADES were evaluated, and lactic acid:glucose (LGH) showed the highest selenium recoveries. Selenium analysis was performed by inductively coupled plasma mass spectrometry (ICP MS). Se-NADES analysis in ICP MS was optimized according to the radio frequency power and nebulization gas flow rate. Se-NADES extraction was optimized by an experimental design. LGH dilution, LGH volume, sample quantity, and ultrasound time were factors influencing the extraction. Seleno-amino acids were determined by liquid chromatography-ICP MS. After optimization, the limits of detection obtained were 7.37, 8.63, and 9.64 µg kg-1 for selenocysteine, selenomethionine, and seleno-methyl-selenocysteine, respectively. The NADES-extraction is a green procedure with 2 penalty points in the EcoScale. The method was applied to the analysis of powdered milk, lyophilized Se-fortified sheep milk, and ERM-BD151 skimmed milk powder.

Effect of gut microflora on nutritional availability of selenium.

Since selenium (Se) is an essential mineral, animals must be able to metabolize the various selenocompounds in meat, fish and vegetables. It is unclear how animals, including humans, utilize selenocompound efficiently, but we hypothesized that gut microflora might contribute to these processes. In this study, we revealed that Se-methylselenocysteine and selenocyanate were metabolized to selenomethionine (SeMet) by intestinal microflora, suggesting selenocompounds might be metabolized to SeMet, which can be used by the host organism. The major urinary selenosugar, 1ß-methylseleno-N-acetyl-d-galactosamine, was utilized less in microflora-suppressed than healthy rats, suggesting that this sugar can be transformed to a nutritionally available form by gut microflora in animals with a healthy microbiota. We concluded that, in rats at least, gut microflora has a role in the metabolism of Se in the host animal, and this finding might be worth investigating in humans.

Distribution and chemical form of selenium in Neptunia amplexicaulis from Central Queensland, Australia.

Selenium (Se), a trace element essential for human and animal biological processes, is deficient in many agricultural soils. Some extremely rare plants can naturally accumulate extraordinarily high concentrations of Se. The native legume Neptunia amplexicaulis, endemic to a small area near Richmond and Hughenden in Central Queensland, Australia, is one of the strongest Se hyperaccumulators known on Earth, with foliar concentrations in excess of 4000 µg Se g-1 previously recorded. Here, we report on the Se distribution at a whole plant level using laboratory micro X-ray Fluorescence Microscopy (µXRF) and scanning electron microscopy (SEM-EDS), as well as on chemical forms of Se in various tissues using liquid chromatography-mass spectrometry (LC-MS) and synchrotron X-ray absorption spectroscopy (XAS). The results show that Se occurs in the forms of methyl-selenocysteine and seleno-methionine in the foliar tissues, with up to 13 600 µg Se g-1 total in young leaves. Selenium was found to accumulate primarily in the young leaves, flowers, pods and taproot, with lower concentrations present in the fine-roots and stem and the lowest present in the oldest leaves. Trichomes were not found to accumulate Se. We postulate that Se is (re)distributed in this plant via the phloem from older leaves to newer leaves, using the taproot as the main storage organ. High concentrations of Se in the nodes (pulvini) indicate this structure may play an important a role in Se (re)distribution. The overall pattern of Se distribution was similar in a non-Se tolerant closely related species (Neptunia gracilis), although the prevailing Se concentrations were substantially lower than in N. amplexicaulis.

Protective Effect of Se-Methylselenocysteine on Elaidic Acid-Induced Inflammation in Human Arterial Endothelial Cells.

This study was designed to investigate the anti-inflammatory effect of Se-methylselenocysteine (MSC) on elaidic acid (9t18:1, EA) induced human arterial endothelial cells (HAECs). MTT and flow cytometry were used to determine cell viability and cell apoptosis respectively. Western blotting was used to assess protein expression of intercellular adhesion molecular 1 (ICAM-1), E-selectin, interleukin-8 (IL-8), endothelial nitric oxide synthase (e-NOS) and phospholipases A2 (PLA2), while enzyme-linked immunosorbent assay (ELISA) was performed to examine the secretion level of nitric oxide (NO). In the cell viability assay, EA significantly decreased cell viability when compared with negative control (NC) group, and MSC effectively reversed this adverse effect, especially at the concentration of 200 µmol/L with 24 h incubation. Also, the same concentration of MSC prevented HAECs cell apoptosis induced by EA. In addition, we found that the expression of ICAM-1, E-selectin, IL-8 and PLA2 were significantly increased and e-NOS decreased in EA group compared with NC group. Inhibition of PLA2 promoted ICAM-1, E-slectin and IL-8 expression in HAECs induced by EA. And MSC down-regulated the secretion of NO level in EA-induced HAECs. Based on these results, we concluded that MSC activated PLA2 which regulated the expression of ICAM-1, E-selectin and IL-8 to protect inflammation induced by EA in HEACs.