Change of choline compounds in sodium selenite-induced apoptosis of rats used as quantitative analysis by in vitro 9.4T MR spectroscopy

AIM: To study liver cell apoptosis caused by the toxicity of selenium and observe the alteration of choline compounds using in vitro 9.4T high resolution magnetic resonance spectroscopy. METHODS: Twenty male Wistar rats were randomly divided into two groups. The rats in the treatment group were intraperitoneally injected with sodium selenite and the control group with distilled water. All rats were sacrifi ced and the livers were dissected. 1H-MRS data were collected using in vitro 9.4T high resolution magnetic resonance spectrometer. Spectra were processed using XWINNMR and MestRe-c 4.3. HE and TUNEL staining was employed to detect and confi rm the change of liver cells. RESULTS: Good 1H-MR spectra of perchloric acid extract from liver tissue of rats were obtained. The conventional metabolites were detected and assigned. Concentrations of different ingredient choline compounds in treatment group vs control group were as follows: total choline compounds,5.08 ± 0.97 mmol/L vs 3.81 ± 1.16 mmol/L (P = 0.05); and free choline,1.07 ± 0.23 mmol/L vs 0.65 ± 0.20 mmol/L (P = 0.00). However,there was no statistical signif icance between the two groups. The hepatic sinus and cellular structure of hepatic cells in treatmentgroup were abnormal. Apoptosis of hepatic cells was confi rmed by TUNEL assay. CONCLUSION: High dose selenium compounds can cause the rat liver lesion and induce cell apoptosis in vivo. High resolution 1H-MRS in vitro can detect diversified metabolism. The changing trend for different ingredient of choline compounds is not completely the same at early period of apoptosis.

Sodium selenite promotes neurological function recovery after spinal cord injury by inhibiting ferroptosis

Ferroptosis is a recently discovered form of iron-dependent cell death,which occurs during the pathological process of various central nervous system diseases or injuries,including secondary spinal cord injury.Selenium has been shown to promote neurological function recovery after cerebral hemorrhage by inhibiting ferroptosis.However,whether selenium can promote neurological function recovery after spinal cord injury as well as the underlying mechanism remain poorly understood.In this study,we injected sodium selenite(3μL,2.5μM)into the injury site of a rat model of T10 vertebral contusion injury 10 minutes after spinal cord injury modeling.We found that sodium selenite treatment greatly decreased iron concentration and levels of the lipid peroxidation products malondialdehyde and 4-hydroxynonenal.Furthermore,sodium selenite increased the protein and mRNA expression of specificity protein 1 and glutathione peroxidase 4,promoted the survival of neurons and oligodendrocytes,inhibited the proliferation of astrocytes,and promoted the recovery of locomotive function of rats with spinal cord injury.These findings suggest that sodium selenite can improve the locomotive function of rats with spinal cord injury possibly through the inhibition of ferroptosis via the specificity protein 1/glutathione peroxidase 4 pathway.

Redifferentiation of Human Gastric Cancer Cells Induced by Ascorbic Acid and Sodium Selenite

Objective To explore the effects and mechanisms of ascorbic acid (AA) and sodium selenite (SS) on growth inhibition and redifferentiation in human gastric cancer cells. Methods In the present study, trypan blue dye exclusion method was used to determine the cell growth curve and mitotic index, cell electrophoresis and colonogenic potential were used as the indexes of redifferentiation. In order to find out the mechanisms of redifferentiation, the activities of superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) were assayed, the content of malondialdehyde (MDA), reduced glutathione (GSH) and H2O2 were evaluated. Results After treatment with AA 3 mol/L + SS 2μmol/L, the growth rate and mitotic index of human gastric cancer cells (MGc-803) decreased remarkably. The indexes related with cell malignancy were alleviated. For example, cell surface charge was obviously decreased, the electrophoresis rate was dropped from 2.21 to 1.15μm·s-1·V-1·cm-1. The indexes related with cell redifferentiation were promoted. For example, the colonogenic potential was decreased to 93.5%. These results indicated that redifferentiation of human gastric cancer cells was successfully induced by AA + SS. The activities of SOD and GPX were significantly higher, while the activity of CAT was slower in treated group than that in the control. The content of MDA was slightly decreased, GSH was sharply decreased, and H2O2 content was dramatically increased. Conclusion These results indicated that combination of ascorbic acid and sodium selenite may induce the redifferentiation of human gastric cancer cells and inhibit cell growth by virtue of enhancing the activities of antioxidative enzymes and inducing the formation of H2O2, and altering the cell redox status. Combination of ascorbic acid and sodium selenite may be a potent anticancer agent for human gastric cancer.

Sodium selenite ameliorates dextran sulfate sodiuminduced chronic colitis in mice by decreasing Th1, Th17, and γδT and increasing CD4(+)CD25(+) regulatory T-cell responses

AIM To assess the effect of sodium selenite on the severity of dextran sulfate sodium(DSS)-induced colitis in C57BL/6 mice.METHODS Mice were randomly divided into four groups(n = 10/group): normal group, selenium(Se) group, chronic colitis group, and Se + chronic colitis group. The mice were sacrificed on day 26. Survival rates, clinical symptoms, colon length, and histological changes were determined. The percentages and absolute numbers of immune system cells in the lamina propria lymphocytes(LPL) of the colon, the expression of m RNA in colon tissue, and the concentrations of Th1, Th17, and Treg cytokines in LPL from the large intestine, were measured.RESULTS Se significantly ameliorated the symptoms of colitis and histological injury(P < 0.05 each), increasing the proportions of neutrophils and CD4+ CD25+ T cells(P < 0.05 each) and decreasing the proportions of γδT cells, CD4+, CD4+CD44+, and CD4+ CD69+ T cells in LPL(P < 0.05 each). Moreover, Se reduced the expression of IL-6, IFN-γ, IL-17 A, IL-21, T-bet, and RORγt(P < 0.05 each), but enhanced the expression of IL-10 and Foxp3(P < 0.05 each). CONCLUSION These results suggest that Se protects against DSSinduced chronic colitis perhaps by increasing the number of CD4(+)CD25(+) Tregs that suppress the secretion of proinflammatory cytokines and populations of Th1, Th17, and γδT cells.

Comparison of the impact of epigallocatechin gallate and ellagic acid in an experimental cataract model induced by sodium selenite

AIM：To compare the potential protective effects of epigallocatechin gallate（EGCG） and ellagic acid（EA） in an experimental cataract model.●METHODS：Twenty-eight Spraque-Dawley rat pups were assigned into four groups.All the rats,except for those in the control group,were injected subcutaneously sodium selenite to induce experimental cataract on the postpartum ninth day,and between 10 th and 14 th days.Rats in the sham,EGCG,and EA groups were intraperitoneally administered 50 mg/（kg·d） saline solution,50 mg/（kg·d） EGCG and 200 mg/（kg·d） EA,respectively.The reduced glutathione（GSH） and malondialdehyde（MDA） levels,total antioxidant status（TAS） and total oxidant status（TOS） in lens supernatants were measured.RESULTS：The mean cataract gradings in EGCG and EA groups were found to be significantly lower than that in sham group（P〈0.001）.The mean GSH levels and TASs in EGCG and EA groups were significantly higher than that in sham group while mean MDA levels and TOSs in EGCG and EA groups were significantly lower than that in the sham group（P〈0.001）.CONCLUSION：EGCG and EA have protective effects on cataract development via the inhibition of oxidative stress.

Protective Role of C-Phycocyanin Against Secondary Changes During Sodium Selenite Mediated Cataractogenesis

Age related cataract is the leading cause of blindness associated with accumulation of oxidative stress in the eye lens.The present investigation reveals the rational of the beneficial effects of the natural compound C-phycocyanin(CPC)is beneficial when administered to rat pups to protect against the secondary effects of sodium selenite induced cataractogenesis.A single subcutaneous dose of sodium selenite(19 lmol/kg body weight)on the 10th day of postpartum is adequate to induce cataract in rat pups.Serum biochemical parameters,such as the level of electrolytes,mean activities of anti-oxidant enzymes i.e.superoxide dismutase,catalase and reduced glutathione were observed to be significantly altered during selenite induced cataractogenic process.Histopathological examination revealed signs of degradation of normal cell architecture in the liver,kidney and eye lens.Interestingly,the deleterious effects of sodium selenite toxicity were restored with the simultaneous treatment with C-PC.The results suggest that an administration of 200 mg/kg body weight of C-PC has the ability to prevent/alter the secondary changes reflected in the serum biochemical and histological modifications in rats exposed to sodium selenite.These results complement the beneficial role of C-PC of cyanobacterial origin as a efficacious anti-cataractogenic agent against sodium selenite toxicity.

Sodium selenite may be not the optimal speciation as an effective therapy for arsenic-induced anxiety-/depression-like behavior

Major depressive disorder is a serious and prevalent neuropsychiatric disorder,affecting more than 350 million people worldwide.Here,sodium selenite(SS)was selected as the selenite supplement to improve the behavior in a mouse model of depression induced by As.SS may be not the optimal speciation for selenite supplementation and the source of the SS used in the study was not disclosed.There are many mouse models of depression and anxiety;however,in the current study,a classical mouse model of depression was not used.Thus,several questions still need to be further discussed.Taken together,the results indicate that SS may be not the optimal speciation as an effective therapy for As-induced anxiety-/depression-like behavior.

Effect of Sodium Selenite-Chitosan Compound Preservative on Storability of Kumquats

[Objectives]To explore the effect of sodium selenite-chitosan compound preservative on storability of kumquats.[Methods]Under the condition of room temperature,fresh kumquats were coated with different concentrations of sodium selenite-chitosan compound preservative,respectively.[Results]Sodium selenite-chitosan compound preservative reduced the weight loss rate,delayed the decline of vitamin C,soluble solids,titratable acid and GSH contents,slowed down the accumulation of MDA,inhibited the increase of PPO activity,and increased to a certain extent the activity of SOD in fresh kumquats.[Conclusions]Sodium selenite-chitosan compound preservative maintained the quality and prolonged the shelf life of kumquats.The preservation effect of compound preservative composed of 4 mg/L sodium selenite and 8 g/L chitosan was the best.

Hydrogen selenide,a vital metabolite of sodium selenite,uncouples the sulfilimine bond and promotes the reversal of liver fibrosis

Sodium selenite has alleviating effects on liver fibrosis;however,its therapeutic molecular mechanism remains unclear.Herein,hydrogen selenide,a major metabolite of Na_(2)SeO_(3),was tested to uncouple the sulfilimine bond in collagen IV,the biomarker of liver fibrosis.A mouse model of liver fibrosis was constructed via a CCl_(4)-induced method,followed by the administration of 0.2 mg kg−1 Na_(2)SeO_(3)via gavage three times per week for 4 weeks.Changes in H2Se,NADPH,and H_(2)O_(2)levels were monitored in real time by using NIR-H2Se,DCI-MQ-NADPH,and H_(2)O_(2)probes in vivo,respectively.H_(2)Se continuously accumulated in the liver throughout the Na_(2)SeO_(3)treatment period,but the levels of NADPH and H_(2)O_(2)decreased.The expression of collagen IV was analyzed through Western blot and liquid chromatography-mass spectrometry.Results confirmed that the sulfilimine bond of collagen IV in the fibrotic mouse livers could be broken by H2Se with the Na_(2)SeO_(3)treatment.Therefore,the therapeutic effect of Na_(2)SeO_(3)on liver fibrosis could be mainly attributed to H_(2)Se that uncoupled the sulfilimine bond to induce collagen IV degradation.This study provided a reasonable explanation for the molecular mechanism of the in vivo function of Na_(2)SeO_(3)and the prevention of liver fibrosis by administering inorganic selenium.

Mechanistic research:Selenium regulates virulence factors,reducing adhesion ability and inflammatory damage of Helicobacter pylori

BACKGROUND The pathogenicity of Helicobacter pylori is dependent on factors including the environment and the host.Although selenium is closely related to pathogenicity as an environmental factor,the specific correlation between them remains unclear.AIM To investigate how selenium acts on virulence factors and reduces their toxicity.METHODS H.pylori strains were induced by sodium selenite.The expression of cytotoxin-associated protein A(CagA)and vacuolating cytotoxin gene A(VacA)was determined by quantitative PCR and Western blotting.Transcriptomics was used to analyze CagA,CagM,CagE,Cag1,Cag3,and CagT.C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction,and H.pylori colonization,inflammatory reactions,and the cell adhesion ability of H.pylori were assessed.RESULTS CagA and VacA expression was upregulated at first and then downregulated in the H.pylori strains after sodium selenite treatment.Their expression was significantly and steadily downregulated after the 5th cycle(10 d).Transcriptome analysis revealed that sodium selenite altered the levels affect H.pylori virulence factors such as CagA,CagM,CagE,Cag1,Cag3,and CagT.Of these factors,CagM and CagE expression was continuously downregulated and further downregulated after 2 h of induction with sodium selenite.Moreover,CagT expression was upregulated before the 3rd cycle(6 d)and significantly downregulated after the 5th cycle.Cag1 and Cag3 expression was upregulated and downregulated,respectively,but no significant change was observed by the 5th cycle.C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction.The extent of H.pylori colonization in the stomach increased;however,sodium selenite also induced a mild inflammatory reaction in the gastric mucosa of H.pylori-infected mice,and the cell adhesion ability of H.pylori was significantly weakened.CONCLUSION These results demonstrate that H.pylori displayed virulence attenuation after the 10th d of sodium selenite treatment.Sodium selenite is a low toxicity compound with strong stability that can reduce the cell adhesion ability of H.pylori,thus mitigating the inflammatory damage to the gastric mucosa.

Selenium: The Cancer Shield

Introduction: Breast cancer is one of the most common types of cancer in the world and the treatments are being improved day by day. Although chemotherapy agents have begun to be used, side effects, resistance development and toxicity seen with these drugs are still steps that limit treatment. Objective: Our aim in this study is to show whether sodium selenate (NaS), which has different effects on many different cells, has antiproliferative and apoptotic effects on MCF-7 breast cancer cells, considering the dose-time relationship, and to reveal its effect on oxidant stress parameters. Methods: 10, 20, 30, 40 and 50 μM sodium selenate was applied to the cells for 24, 48 and 72 hours. MTT test was applied to show the proliferative effect. Apoptosis was also measured with Annexin V/7AAD in MCF7 cells. Malondaldehyde (MDA) and Glutathione (GSH) levels were studied to reveal the oxidant/antioxidant balance. Results: It has been shown that as the NaS dose increases in MCF-7 cells, cell viability decreases (p 0.05), but at all subsequent increasing NaS doses, viability was found statistically significant decreased (p: 0.001, p 0.05, respectively). Conclusion: Considering that NaS has an antitumor effect on breast cancer, increases oxidative stress and increases apoptosis by supressing the antioxidant protection system, and does not have a toxic effect on normal body cells at certain doses. When all these features evaluated, we think, selenium should be considered as a natural option in the treatment of breast cancer.

A study on Se application for improving the soil in the environment at lower Se level

A result that application of sodium selenite or fly ash to some of soilin loess plateau can increase Se content in wheat grain has been demonstrated by the pot and field experiments, and added Se in soil can last its availability for 3 years. So this is a good measure for improving the low Se soils and preventing the Kaschin-Beck disease.

Effects of selenium on electrophysiological changes associated with diabetic peripheral neuropathy

Our previous study has demonstrated that sodium selenite prevents oxidative stress, suggesting that selenium can improve diabetic peripheral neuropathy. Results from this study demonstrated that diabetes mellitus resulted in significant increased time to peak, as well as rheobase and chronaxie values. In addition, maximum depolarization, area under compound action potential, kinetics, and conduction velocities of fast and slow nerve fiber groups were decreased. Sodium selenite exhibited positive effects on alterations of diabetes mellitus-induced conduction velocity distribution. This neuroprotective effect was primarily observed in the area under compound action potential and compound action potential kinetic waveforms, as well as rheobase and chronaxie. Results from this study showed that selenium supplementation blocked the diabetes mellitus-induced shift of actively contributing nerve fibers, and restored levels towards age-matched control group values. Chronic selenate supplementation for experimental diabetic peripheral neuropathy exhibited protective effects in measured electrophysiological parameters.

Relationship between reactive oxygen species and sodium-selenite-induced DNA damage in HepG2 cells

Selenium compounds,as an effective chemopreventive agent,can induce apoptosis in tumor cells.Reactive oxygen species(ROS)are important mediators in apoptosis induced by various stimuli,which include chemopreventive agents.In this study,we investigated the relationship between ROS and the levels of DNA damage induced by selenite in HepG2 cells.After HepG2 cells were treated with selenite,there was a dose-dependent decrease in cell viability.The levels of ROS induced by selenite were measured by 2p,7p-dichlorofluorescein diacetate(DCFH-DA)fluorescence,which shows a dose-and time-dependent increase in HepG2 cells.The levels of DNA damage in HepG2 increased in all cells treated with an increasing dose of selenite at 0,2.5,5,10,and 20μmol/L.N-acetylcysteine(NAC),a known antioxidant,increased cell viability and decreased ROS generation.Moreover,NAC effectively blocked DNA damage induced by selenite.These results revealed that ROS might play an important role in selenite-induced DNA damage that can be reduced by NAC treatment.

Mycelial Growth of Pleurotus Spp in Se-Enriched Culture Media

Selenium (Se) is an essential element to human. However, this element can be in low content in soil of some regions. Se deficiency may cause Keshan disease, thyroid dysfunction and osteoarthritis. The Se-enriched cereals are an interesting way to prevent these diseases. But, recent studies have shown that Se-enriched mushrooms are a better Se source. This occurs due to the high capacity of the fungi to absorb and transform the inorganic Se to organic forms, which are more bioavailable. Pleurotus ostreatus and Pleurotus eryngii are mushrooms species worldwide consumed and able to Se bioaccumulate. However, depending on the level of this element, it can be toxic for the fungus. Here we showed that the presence of the Se in culture medium decreases fungal growth rate, hyphae diameter and septum distance and causes alteration in color of colony. A garlic strong smell was directly proportional to Se level. P. eryngii was more tolerant to Se than P. ostreatus. So, it is important to screen this element level for Se-enriched mushroom production.

Selenium-modified bone cement promotes osteoporotic bone defect repair in ovariectomized rats by restoring GPx1-mediated mitochondrial antioxidant functions

Over-accumulation of reactive oxygen species(ROS)causes mitochondrial dysfunction and impairs the osteogenic potential of bone marrow-derived mesenchymal stem cells(BMMSCs).Selenium(Se)protects BMMSCs from oxidative stress-induced damage;however,it is unknown whether Se supplementation can promote the repair of osteoporotic bone defects by rescuing the impaired osteogenic potential of osteoporotic BMMSCs(OP-BMMSCs).In vitro treatment with sodium selenite(Na_(2)SeO_(3))successfully improved the osteogenic differentiation of OP-BMMSCs,as demonstrated by increased matrix mineralization and up-regulated osteogenic genes expression.More importantly,Na_(2)SeO_(3) restored the impaired mitochondrial functions of OP-BMMSCs,significantly up-regulated glutathione peroxidase 1(GPx1)expression and attenuated the intracellular ROS and mitochondrial superoxide.Silencing of Gpx1 completely abrogated the protective effects of Na_(2)SeO_(3) on mitochondrial functions of OP-BMMSCs,suggesting the important role of GPx1 in protecting OP-BMMSCs from oxidative stress.We further fabricated Se-modified bone cement based on silk fibroin and calcium phosphate cement(SF/CPC).After 8 weeks of implantation,Se-modified bone cement significantly promoted bone defect repair,evidenced by the increased new bone tissue formation and enhanced GPx1 expression in ovariectomized rats.These findings revealed that Se supplementation rescued mitochondrial functions of OP-BMMSCs through activation of the GPx1-mediated antioxidant pathway,and more importantly,supplementation with Se in SF/CPC accelerated bone regeneration in ovariectomized rats,representing a novel strategy for treating osteoporotic bone fractures or defects.

Effect of different forms of selenium in osteoporosis rat model induced by retinoic acid

Osteoporosis is a typical physiological disease,the main symptoms of which are brittle fracture,bone pain and easily deformed.As an individual ages,the prevalence of osteoporosis increases year by year.In the present study,selenium with antioxidant,immunomodulatory and anti-tumor effects was used to prevent osteoporosis induced by retinoic acid.The serum calcium contents in the selenium-treated groups(sodium selenite and selenomethionine)were significantly higher(P<0.05)than those in the model group in both the prevention and treatment studies.After pre-vention,glutamic-oxalacetic transaminase transaminase(GOT),glutamate transaminase(GPT),alkaline phosphatase(ALP)and tartrate-resistant acid phosphatase(TRACP)levels were significantly(P<0.05)decreased.In the treatment study,the serum calcium and phosphorus contents of the rats increased after selenium treatment.There was no significant change(P>0.05)in the activity of GOT and GPT.The content of ALP decreased obviously and the TRACP enzyme activity increased.Overall,these results showed that different forms of selenium compounds have great potential in preventing and treating osteoporosis.