Association between dietary selenium intake and the prevalence of osteoporosis and its role in the treatment of glucocorticoid-induced osteoporosis.

BACKGROUND: Long-term glucocorticoid therapy may lead to osteoporosis (OP). Selenium (Se) is an essential microelement for human health and bone health. This study evaluated the association between dietary Se intake and the prevalence of OP and further explored the potential therapeutic effect of Se on glucocorticoid-induced OP (GIOP) in vivo and in vitro. METHODS: Data were collected from a population-based cross-sectional study conducted in our hospital. OP is diagnosed based on bone mineral density (BMD) measurements using compact radiographic absorptiometry. Dietary Se intake was assessed using a semi-quantitative food frequency questionnaire. The association between dietary Se intake and OP prevalence was analyzed by multivariable logistic regression. In animal experiments, male Sprague-Dawley rats were intramuscularly injected with dexamethasone (1 mg/kg) daily to induce GIOP, while different doses of Se were supplemented in rat drinking water for 60 d. BMD and biomechanical parameters of rat femur were measured. The histopathological changes of the femur were observed by HE staining, the number of osteoclasts was observed by TRAP staining, and OCN positive expression was detected by immunohistochemical staining. OPG, RANKL, Runx2, and BMP2 in rat femur were detected by Western blot. Bone turnover markers and oxidative stress markers were measured using commercial kits. MC3T3-E1 cells were induced to osteogenic differentiation, stimulated with DXM (100 µM), and/or treated with Se at different doses. Cell proliferation and apoptosis were assessed by CCK-8 and flow cytometry. ALP activity was detected by ALP staining and cell mineralization was observed by alizarin red staining. RESULTS: Participants with lower dietary Se intake had higher OP prevalence. Se supplementation improved BMD, biomechanical parameters, and histopathological changes of the femur in GIOP rats. Se supplementation also suppressed DXM-induced changes in bone turnover- and oxidative stress-related markers. Under DXM conditions, Se treatment induced MC3T3-E1 cell proliferation, ALP activity, and mineralization. CONCLUSION: Lower Dietary Se intake is associated with OP prevalence. Moreover, Se takes a position in bone protection and anti-oxidative stress in GIOP models. Therefore, Se may be a complementary potential treatment for GIOP.

Efficacy of selenium supplementation for mild-to-moderate Graves' ophthalmopathy in a selenium-sufficient area (SeGOSS trial): study protocol for a phase III, multicenter, open-label, randomized, controlled intervention trial.

BACKGROUND: The therapeutic effect of selenium has been demonstrated in mild Graves' ophthalmopathy (GO) in a European region where selenium status is suboptimal. However, there is a lack of evidence to support selenium use in selenium-sufficient areas. The aim of this study is to evaluate the therapeutic effect of selenium in mild-to-moderate GO in selenium-sufficient South Korea. METHODS: The SeGOSS trial is a multicenter, prospective, randomized, open-label trial in South Korea. Eighty-four patients aged 19 years or older with mild-to-moderate GO will be randomized to receive either vitamin B complex alone or vitamin B complex with selenium for 6 months with three monthly follow-up visits. The primary outcome is comparison of the improvement in quality of life at 6 months from baseline between the control and selenium groups. The secondary outcomes are intergroup differences in changes in quality of life at 3 months, clinical activity of GO at 3 and 6 months, thyroid autoantibody titers at 3 and 6 months, and the response rate at 3 and 6 months from baseline. Quality of life will be measured by questionnaire for patients with GO, and the clinical activity of GO will be evaluated by the clinical activity score (CAS). A positive response is defined as either changes in the CAS < 0 or the changes in the GO-QOL score ≥ 6. DISCUSSION: The SeGOSS study will evaluate the therapeutic potential of selenium for mild-to-moderate GO in a selenium-sufficient area and provide support in tailoring better treatment for GO. TRIAL REGISTRATION: KCT0004040. Retrospectively registered on 5 June 2019. https://cris.nih.go.kr/cris/search/detailSearch.do/14160 .

Comparative analysis of various sources of selenium on the growth performance and antioxidant status in broilers under heat stress / Análise comparativa de várias fontes de selênio no desempenho de crescimento e status antioxidante em frangos de corte sob estresse térmico

The supplementation of Selenium-enriched probiotics is effective in reducing oxidative stress and maintaining meat quality stability in broiler chicken especially under heat stress. An experimental study was conducted to perform Comparative analysis of Selenium yeast with inorganic Se in broilers under heat stress. A total of 120 broilers chicks of one day were assigned to 4 groups each consisting 30 chicks fed on same basal diet but different selenium sources. The basal diet of group D1 was not supplemented with Se source (Negative control), group D2 basal diet was supplemented with inorganic selenium (Sodium selenite 0.22mg/Kg starter phase and 0.15mg/Kg finisher phase), group D3 basal diet was supplemented with commercially available organic selenium (Seleno-methionine 0.22mg/Kg starter phase and 0.15mg/Kg finisher phase) and group D4 basal diet was supplemented with self-developed organic selenium (Se-enriched yeast 0.22mg/Kg starter phase and 0.15mg/Kg finisher phase). The performance parameters i.e. feed intake (FI), live body weight (BW) and FCR were not significantly (p>0.05) effected by selenium supplementation in the starter phase but were significantly (p<0.05) effected in the finisher phase. Selenium supplementation significantly (p<0.05) effected serum Se level in different supplemented groups. Higher serum Se value (58.20±0.06) was recorded in D4 group. Similarly significantly lower selenium value was recorded for D4 and higher was recorded for D1 (11.36±0.08). However lower serum Paraoxonase (PON) value was recorded for D4 (13.24±0.01) and higher for D1 (13.33±0.03). Comparatively self-developed Se enriched yeast increased the Se accumulation and improved antioxidant system. Glutathione peroxidase (GPx) was found higher in D4 (12.333±0.03) followed by D3, D2 and D1 respectively. Whereas superoxide dismutase (SOD) was significantly lower (p<0.05) in D4 (0.1437±0.003) followed by D3 (0.1457±0.002). Selenium supplementation increased the [...].

A suplementação de probióticos enriquecidos com selênio é eficaz na redução do estresse oxidativo e na manutenção da estabilidade da qualidade da carne em frangos de corte, especialmente sob estresse por calor. Um estudo experimental foi conduzido para realizar uma análise comparativa da levedura selênio com o Se inorgânico em frangos de corte sob estresse térmico. Um total de 120 pintos de um dia foi dividido em 4 grupos, cada um consistindo de 30 pintos alimentados com a mesma dieta basal, mas com diferentes fontes de selênio. A dieta basal do grupo D1 não foi suplementada com fonte de Se (controle negativo), a dieta basal do grupo D2 foi suplementada com selênio inorgânico (selenito de sódio 0,22 mg / kg fase inicial e 0,15 mg / kg fase finalizadora), a dieta basal do grupo D3 foi suplementada com selênio orgânico disponível comercialmente (fase inicial de seleno-metionina 0,22 mg / kg e fase finalizadora de 0,15 mg / kg) e a dieta basal do grupo D4 foi suplementada com selênio orgânico autodesenvolvido (fermento enriquecido com Se 0,22 mg / kg fase inicial e 0,15 mg / kg fase finalizadora). Os parâmetros de desempenho, ou seja, consumo de ração (FI), peso corporal vivo (PC) e FCR não foram significativamente (p > 0,05) afetados pela suplementação de selênio na fase inicial, mas foram significativamente (p < 0,05) afetados na fase final. A suplementação de selênio afetou significativamente (p < 0,05) o nível de Se sérico em diferentes grupos suplementados. O maior valor de Se sérico (58,20 ± 0,06) foi registrado no grupo D4. Da mesma forma, valor de selênio significativamente menor foi registrado para D4 e maior foi registrado para D1 (11,36 ± 0,08). No entanto, um valor mais baixo de Paraoxonase (PON) sérica foi registrado para D4 (13,24 ± 0,01) e mais alto para D1 (13,33 ± 0,03). A levedura enriquecida com Se comparativamente autodesenvolvida aumentou o acúmulo de Se e melhorou o sistema [...].

Transgenerational effects of zinc, selenium and chromium supplementation on glucose homeostasis in female offspring of gestational diabetes rats.

Clinical studies have demonstrated that maternal gestational diabetes mellitus (GDM) increases the offspring's risk of developing glucose intolerance. Our previous study reported that co-supplementation with zinc, selenium, and chromium improved insulin resistance in diet-induced GDM rats. Here, Transgenerational effects of supplementation with zinc (10 mg/kg.bw), selenium (20 µg/kg.bw), and chromium (20 µg/kg.bw) in F1 female offspring of both zinc, selenium and chromium (ZnSeCr)-treated, and untreated GDM rats daily by gavage from weaning to the postpartum were investigated in the present study. Glucose homeostasis in the F1 female offspring of GDM at different stages were evaluated. Maternal GDM did increase the birth mass of newborn F1 female offspring, as well as the serum glucose and insulin levels. Zinc, selenium and chromium supplementation attenuated the GDM-induced mass gain, increased serum glucose and insulin levels in the female neonates. The high fat and sucrose (HFS) diet-fed GDM-F1 offspring developed GDM, with glucose intolerance, hyperglycemia and insulin resistance during pregnancy. Moreover, endoplasmic reticulum (ER) stress-related protein levels were increased and the activation of insulin signaling pathways were reduced in the liver of HFS-fed GDM-F1 offspring. Whereas glucose homeostasis in parallel with insulin sensitivity was normalized in the female offspring of GDM by supplementation both F0 dams and F1 offspring with zinc, selenium and chromium, not in those either F0 or F1 elements supplemented offspring. Therefore, we speculate that zinc, selenium and chromium supplementation may have a potential beneficial transgenerational effect on the glucose homeostasis in the female offspring of GDM.

Sodium selenite and Se-enriched yeast supplementation in atherosclerotic patients: Effects on the expression of pyroptosis-related genes and oxidative stress status.

BACKGROUND AND AIMS: Atherosclerosis as a chronic inflammatory disorder of the arterial wall is the main leading cause of the cardiovascular disease (CVD). Caspase-dependent pyroptosis plays a pivotal role in the pathogenesis of CVD. Selenium (Se) is an important component of the antioxidant defense and plays a crucial role in cardiovascular health. This study aimed to investigate the effects of daily consumption of sodium selenite and Se-enriched yeast on the expression of pyroptosis-related genes, and biomarkers of oxidative stress in patients with atherosclerosis. METHODS AND RESULTS: In this randomized, double-blinded, placebo-controlled clinical trial, 60 patients with atherosclerosis were recruited. Participants received 200 µg/day of sodium selenite, Se-enriched yeast, or placebo for 8 following weeks. The pyroptosis-related genes' mRNA expression in peripheral blood mononuclear cells (PBMCs) was assessed before and after the intervention. Also, the levels of superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), and glutathione peroxidases (GPX) were measured at baseline and following the intervention. Following sodium selenite and Se-enriched yeast supplementation, the relative expression levels of TLR4, ASC, NLRP3, and NF-κB1 were significantly downregulated (p < 0.05). Furthermore, the changes in GPX were significantly increased after selenite and yeast supplementation (p < 0.05). Also, selenite and yeast consumption caused a statistically significant decrease in the change of MDA level (p < 0.05). CONCLUSION: In summary, these findings showed that Se supplementation may reduce inflammation through down-regulation of some pro-inflammatory genes, improving antioxidant defenses in atherosclerosis patients. Further research is required to come to a definite conclusion of selenium supplementation on the CVD risk. This study was registered on the Iranian Registry of Clinical Trials website (identifier: RCT20110123005670N28; https://www.irct.ir/).

Selenium attenuates the cadmium-induced placenta glucocorticoid barrier damage by up-regulating the expression of specificity protein 1.

Cadmium (Cd) is an environmental pollutant and pregnant women are especially susceptible to the effects of exposure to Cd. Our previous study found Cd can be accumulated in the placenta and causes fetal growth restriction (FGR) through damage the placental glucocorticoid barrier. Selenium (Se), as an essential micronutrient, can allivate Cd-induced toxicity. In this study, we aim to explore the protective mechanism of Se against Cd-induced the placental glucocorticoid barrier damage and FGR. Pregnant Sprague Dawley (SD) rats were exposed to CdCl2 (1 mg/kg/day) and Na2 SeO3 (0.1-0.2-0.3 mg/kg/day) by gavage from gestational day (GD) 0 to GD 19. The results showed that reduced fetal weight, increased corticosterone concentrations in the maternal and fetal serum, and impaired placental labyrinth layer blood vessel development, appeared in pregnant rats after Cd exposure and improved after treated with Se. In cell experiments, we confirmed that Se reduces Cd-induced apoptosis. Moreover, Se can abolish Cd-induced 11ß-HSD2 and specificity protein 1 (Sp1) decreasing in vivo and vitro. In human JEG-3 cells, the knockdown of Sp1 expression by small interfering RNA can suppressed the protective effect of Se on Cd-induced 11ß-HSD2 decreasing. In general, our results demonstrated that Se is resistant to Cd-induced FGR through upregulating the placenta barrier via activation of the transcription factor Sp1.

A Transcriptomic Analysis of T98G Human Glioblastoma Cells after Exposure to Cadmium-Selenium Quantum Dots Mainly Reveals Alterations in Neuroinflammation Processes and Hypothalamus Regulation.

Quantum dots are nanoparticles with very promising biomedical applications. However, before these applications can be authorized, a complete toxicological assessment of quantum dots toxicity is needed. This work studied the effects of cadmium-selenium quantum dots on the transcriptome of T98G human glioblastoma cells. It was found that 72-h exposure to 40 µg/mL (a dose that reduces cell viability by less than 10%) alters the transcriptome of these cells in biological processes and molecular pathways, which address mainly neuroinflammation and hormonal control of hypothalamus via the gonadotropin-releasing hormone receptor. The biological significance of neuroinflammation alterations is still to be determined because, unlike studies performed with other nanomaterials, the expression of the genes encoding pro-inflammatory interleukins is down-regulated rather than up-regulated. The hormonal control alterations of the hypothalamus pose a new concern about a potential adverse effect of quantum dots on fertility. In any case, more studies are needed to clarify the biological relevance of these findings, and especially to assess the real risk of toxicity derived from quantum dots exposure appearing in physiologically relevant scenarios.

Cardiovascular protective effect of nano selenium in hypothyroid rats: protection against oxidative stress and cardiac fibrosis.

BACKGROUND: Nano selenium (Nano Sel) has many therapeutic properties including antioxidant, anticancer, and anti-inflammatory actions. OBJECTIVE: Impacts of Nano Sel administration against cardiac fibrosis and heart and aorta tissue oxidative damage observed in hypothyroid rats were explored. METHODS: The animals were randomly grouped and treated as: 1) Control; 2) Propylthiouracil (PTU) in which PTU was added to the drinking water (0.05%) to induce hypothyroidism; 3-5) PTU-Nano Sel 50, PTU-Nano Sel 100, and PTU-Nano Sel 150 groups, which received daily PTU plus 50,100 or 150 µg/kg of Nano Sel for 6 weeks intraperitoneally. The heart and aorta tissues were removed under deep anesthesia and then biochemical parameters including malondialdehyde (MDA), total thiol groups, catalase (CAT), and superoxide dismutase (SOD), as well as cardiac fibrosis were assessed. RESULTS: Hypothyroidism induced by PTU was remarkably associated with myocardial hypertrophy and perivascular fibrosis in Masson's trichrome staining. Moreover, hypothyroidism increased MDA level, while it subtracted total thiol group content and activity of SOD and CAT. Treatment with Nano Sel recovered hypothyroidism-induced cardiac fibrosis in the histological assessment. Nano Sel also promoted CAT and SOD activity and thiol content, whereas alleviated MDA levels in the heart and aorta tissues. CONCLUSION: Results propose that administration of Nano Sel exerts a protective role in the cardio vascular system via preventing cardiac fibrosis and inhibiting oxidative stress.

Editorial to Special Issue Molecular Biology of Selenium in Health and Disease.

The selenium field expanded at a rapid rate for about 45 years, from the mid-1970's until about 2015 (see [...].

Possible protective and curative effects of selenium nanoparticles on testosterone-induced benign prostatic hyperplasia rat model.

BACKGROUND: Men over the age of 40 are more likely to develop benign prostatic hyperplasia (BPH). BPH is characterised by proliferation of the prostatic epithelium and stroma. Selenium in the form of nanoparticles is an essential metalloid mineral and antioxidant. In this study, selenium nanoparticles (SeNPs) were tested for their potential protective and curative impacts on BPH in rats. MATERIALS AND METHODS: Fifty male Sprague-Dawley rats were randomly divided into five groups: Group I (Control group); Group II (Orchiectomised group): bilateral orchiectomy was conducted on rats; Group III (BPH group): testosterone (TE) enanthate injection was used to induce BPH; Group IV (Protective group): rats were given SeNPs before subjecting rats to BPH; Group V (Curative group): rats were succumbed to BPH, followed by administration of SeNPs. Measurement of prostate specific antigen (PSA) and TE in serum was performed and prostates were weighed and prepared for histological, immunohistochemical and ultrastructural examination. RESULTS: In the BPH group, serum TE and PSA levels, as well as prostate weight, increased significantly and significant decreases were observed in the protective and curative groups. Reduced acinar lumen, expansion of stroma and epithelial hyperplasia were noticed in the BPH group, which were ameliorated significantly in both the protective and curative groups. There was an increase in proliferating cell nuclear antigen immunoreaction in the BPH group and a decrease in both the protective and curative groups. On transmission electron microscopy of BPH group, the nuclei appeared irregular with dilated endoplasmic reticulum, loss of cell boundaries and apical microvilli. The protective group showed more improvement than the curative group. CONCLUSIONS: The effects of SeNPs on BPH induced by TE in rats, were both protective and curative, although the protective effects were more pronounced.

Selenium and cancer risk: Wide-angled Mendelian randomization analysis.

Evidence on the association between selenium and cancer risk is inconclusive. We conducted a Mendelian randomization study to examine the associations of selenium levels with 22 site-specific cancers and any cancer. Single nucleotide polymorphisms (SNPs) strongly associated with toenail and blood (TAB) and blood selenium levels in mild linkage disequilibrium (r2 < .3) were used as instrumental variables. Genetic associations of selenium-associated SNPs with cancer were obtained from the UK Biobank including a total of 59 647 cancer cases and 307 914 controls. Associations with P < .1 in UK Biobank were tested for replication in the FinnGen consortium comprising more than 180 000 individuals. The inverse-variance weighted method accounting for linkage disequilibrium was used to estimate the associations. Genetically predicted TAB selenium levels were not associated with the risk of the 22 site-specific cancers or any cancer (all 22 site-specific cancers). Similarly, we observed no strong association for genetically predicted blood selenium levels. However, genetically predicted blood selenium levels showed suggestive associations with risk of kidney cancer (odds ratio [OR] per one-unit increase in log-transformed levels: 0.83; 95% confidence interval [CI]: 0.67-1.03) and multiple myeloma (OR: 1.40; 95% CI: 1.02-1.93). The same direction of association for kidney cancer but not for multiple myeloma was observed in FinnGen. In the metaanalysis of UK Biobank and FinnGen, the OR of kidney cancer was 0.83 (95% CI: 0.69-1.00). Our study suggests that high selenium status may not prevent cancer development. The associations for kidney cancer and multiple myeloma need to be verified in well-powered studies.

Formation Mechanism and Toxicological Significance of Biogenic Mercury Selenide Nanoparticles in Human Hepatoma HepG2 Cells.

It is widely recognized that the toxicity of mercury (Hg) is attenuated by the simultaneous administration of selenium (Se) compounds in various organisms. In this study, we revealed the mechanisms underlying the antagonistic effect of sodium selenite (Na2SeO3) on inorganic Hg (Hg2+) toxicity in human hepatoma HepG2 cells. Observations by transmission electron microscopy indicated that HgSe (tiemannite) granules of up to 100 nm in diameter were accumulated in lysosomal-like structures in the cells. The HgSe granules were composed of a number of HgSe nanoparticles, each measuring less than 10 nm in diameter. No accumulation of HgSe nanoparticles in lysosomes was observed in the cells exposed to chemically synthesized HgSe nanoparticles. This suggests that intracellular HgSe nanoparticles were biologically generated from Na2SeO3 and Hg2+ ions transported into the cells and were not derived from HgSe nanoparticles formed in the extracellular fluid. Approximately 85% of biogenic HgSe remained in the cells at 72 h post culturing, indicating that biogenic HgSe was hardly excreted from the cells. Moreover, the cytotoxicity of Hg2+ was ameliorated by the simultaneous exposure to Na2SeO3 even before the formation of insoluble HgSe nanoparticles. Our data confirmed for the first time that HepG2 cells can circumvent the toxicity of Hg2+ through the direct interaction of Hg2+ with a reduced form of Se (selenide) to form HgSe nanoparticles via a Hg-Se soluble complex in the cells. Biogenic HgSe nanoparticles are considered the ultimate metabolite in the Hg detoxification process.

Dietary selenium intake and risk of hospitalization for type 2 diabetes in the Moli-sani study cohort.

BACKGROUND AND AIMS: Experimental and non-experimental human studies have consistently shown a positive association between exposure to the trace element selenium, which occurs primarily through diet, and risk of type 2 diabetes mellitus. Plausible biological mechanisms include adverse effects of selenium and selenium-containing proteins on glucose metabolism. However, the levels of exposure above which risk increases are uncertain. METHODS AND RESULTS: We examined the association between selenium intake and first hospitalization for type 2 diabetes during a median follow-up period of 8.2 years among 21,335 diabetes-free participants in the Moli-sani cohort, Italy. Selenium intake was ascertained at baseline using a food frequency questionnaire, showing a median value of 59 µg/day. During follow-up, we identified 135 incident cases of hospitalization for diabetes, based on population-based hospital discharge data. We used a Cox proportional hazards model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for hospitalization for diabetes, adjusting for potential confounders. HRs (95% CIs) were 1.01 (0.60-1.70), 1.13 (0.66-1.96) and 1.75 (0.99-3.10) comparing the second, third, and fourth sex-specific quartiles with the first quartile, respectively. Risk was 64% greater in the fourth quartile as compared with the previous three. Spline regression analysis also indicated a steeper increase in risk occurring among men compared with women. CONCLUSIONS: In a large population of Italian adults free of type 2 diabetes at cohort entry, high dietary selenium intake was associated with increased risk of hospitalization for diabetes.

Effect of Selenium on Quantitative Structural Changes in Dexamethasone-Induced Immunodeficiency Rat Models.

Background: One of the major indices of immunodeficiency is lymphoid organ atrophy. Some trace elements are candidates for the treatment of this defect. These conditions may induce structural changes in the sub-components of lymphoid organs. Therefore, this study evaluated the effect of selenium on volumetric changes in dexamethasone (DEX)-induced lymphoid organ atrophy in an animal model. Methods: This study was conducted at Histomorphometry and Stereology Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran, in September 2016 to September 2017. Thirty-two male rats were divided into four groups: Group I; control (normal saline, 0.5 mL/kg, intraperitoneally), Group II; DEX (0.4 mg/kg; intraperitoneally), Group III; selenium plus DEX (similar to Group II and Group IV), and Group IV; selenium (0.1 mg/kg; orally). At the end of the experiment, the rats' thymus, spleen, and lymph nodes were removed, processed, and stained by hematoxylin and eosin (H&E). The volume and volume density of theses organs were estimated by stereology. The results were analyzed using the Mann-Whitney U-test and the Kruskal-Wallis test. Results: The volume of the thymus as well as its cortex and medulla; the volume of the spleen as well as the volume density of its white pulp, periarterial lymphatic sheath zone, and follicles; and the volume of the lymph nodes as well as their inner (P=0.001) and outer (P=0.007) cortices showed a significant reduction in the DEX-treated animals in comparison with the controls. In the DEX plus selenium-treated animals, maximum effects were observed on the increment in the thymic cortex (P=0.001), the outer cortex of the lymph nodes (P=0.012), and the splenic follicles (P=0.018) in comparison with the DEX group. There was no significant difference between the animals receiving selenium treatment and the controls in terms of lymphoid organs. Conclusion: Selenium may improve lymphoid organ structures in an immunodeficiency rat model but has no effect on normal lymphoid tissues.

Abatement of the dysfunctional hypothalamic-pituitary-gonadal axis due to ciprofloxacin administration by selenium in male rats.

The present study examined the influence of selenium on ciprofloxacin-mediated reproductive dysfunction in rats. The research design consisted of five groups of eight animals each. The rats were administered 135 mg/kg body weight of ciprofloxacin per se or simultaneously with selenium at 0.25 and 0.5 mg/kg for 15 uninterrupted days. Antioxidant and inflammatory indices were assayed using the testes, epididymis, and hypothalamus of the animals after sacrifice. Results revealed that ciprofloxacin treatment per se interfered with the reproductive axis as demonstrated by diminished serum hormonal levels, sperm quality, and enzymatic indices of testicular function, which were, however, abrogated following selenium co-treatment. Besides this, administration of selenium attenuated the depletion of glutathione level, inhibition of catalase, superoxide dismutase, glutathione-S-transferase and glutathione peroxidase activities with a concomitant reduction in reactive oxygen and nitrogen species, and lipid peroxidation in ciprofloxacin-treated in rats. Selenium treatment also mitigated ciprofloxacin-mediated elevation in nitric oxide level and of myeloperoxidase activity as well as histological lesions in the animals. Overall, selenium attenuated impairment in the male reproductive axis due to ciprofloxacin treatment through abatement of inflammation and oxidative stress in rats.

Selenium Status in Diet Affects Acetaminophen-Induced Hepatotoxicity via Interruption of Redox Environment.

Aims: Drug-induced liver injury, especially acetaminophen (APAP)-induced liver injury, is a leading cause of liver failure worldwide. Mouse models were used to evaluate the effect of microelement selenium levels on the cellular redox environment and consequent hepatotoxicity of APAP. Results: APAP treatment affected mouse liver selenoprotein thioredoxin reductase (TrxR) activity and glutathione (GSH) level in a dose- and time-dependent manner. Decrease of mouse liver TrxR activity and glutathione level was an early event, and occurred concurrently with liver damage. The decreases in the GSH/glutathione disulfide form (GSSG) ratio and TrxR activity, and the increase of protein S-glutathionylation were correlated with the APAP-induced hepatotoxicity. Moreover, in APAP-treated mice both mild deprivation and excess supplementation with selenium increased the severity of liver injury compared with those observed in mice with normal dietary selenium levels. An increase in the oxidation state of the TrxR-mediated system, including cytosolic thioredoxin1 (Trx1) and peroxiredoxin1/2 (Prx1/2), and mitochondrial Trx2 and Prx3, was found in the livers from mice reared on selenium-deficient and excess selenium-supplemented diets upon APAP treatment. Innovation: This work demonstrates that both Trx and GSH systems are susceptible to APAP toxicity in vivo, and that the thiol-dependent redox environment is a key factor in determining the extent of APAP-induced hepatotoxicity. Dietary selenium and selenoproteins play critical roles in protecting mice against APAP overdose. Conclusion: APAP treatment in mice interrupts the function of the Trx and GSH systems, which are the main enzymatic antioxidant systems, in both the cytosol and mitochondria. Dietary selenium deficiency and excess supplementation both increase the risk of APAP-induced hepatotoxicity.

The role of selenium in cell survival and its correlation with protective effects against cardiovascular disease: A literature review.

Selenium is a trace element that provides protection against cellular damage and death. Previous research using several types of cells identified anti-oxidant, anti-inflammatory, and anti-apoptotic effects for selenium. One of the diseases related to selenium is cardiovascular disease, as low selenium intake has been linked to cardiomyopathy. However, the mechanism of the cardioprotective effects of selenium is not thoroughly understood. Several studies supported the possible effects of selenium on heart cell survival. In this review, we analyzed recent research (2015-2020) on the roles and mechanism of action of selenium in cell survival and its cardioprotective effects. Furthermore, the prevention of apoptosis through both intrinsic and extrinsic pathways is discussed in this review. Signalling pathways that regulate cell survival such as the p-AMPK, poly (ADP-ribose) polymerase-1, nuclear factor-erythroid 2-related factor-2, AKT/PI3K, and STAT pathways are involved in the protective effects of selenium. In addition, signaling pathways that affect heart cell survival include the AKT and STAT pathways. It also affects autophagy through the PPAR-γ pathway. These findings should facilitate further research on the cardioprotective effects of selenium.

Assessing the Health Loss from Kashin-Beck Disease and Its Relationship with Environmental Selenium in Qamdo District of Tibet, China.

Kashin-Beck Disease (KBD) is one of major endemic diseases in China. In this study, we estimated the health loss from KBD in Qamdo district of Tibet using the years lived with disability (YLD) metric and investigated the influence of environmental selenium (Se) on it by multiple regression model. The results showed that YLD rates produced a different ranking of health loss of KBD from that produced by prevalence rates between Basu and Luolong County, with higher health loss from KBD (43.61 YLD/1000) but lower prevalence (17.86%) in Basu County. YLD rates in two counites were both highest for the 45-64 years age group. Compared with the prevalence rate, the YLD rate had a closer relation to environmental Se and was significantly negatively correlated with Se in both soil and highland barley. The multiple linear regression further revealed that Se contents in cultivated soil and highland barley were main influencing factors for the health loss of KBD, which could explain 90.5% of the variation in YLD rates. The information obtained highlights the significance of the YLD metric in exploring the environmental etiology of KBD and provides important information on which to base decisions on future prevention and control of endemic diseases.

Comparative efficacy of selenate and selenium nanoparticles for improving growth, productivity, fruit quality, and postharvest longevity through modifying nutrition, metabolism, and gene expression in tomato; potential benefits and risk assessment.

This study attempted to address molecular, developmental, and physiological responses of tomato plants to foliar applications of selenium nanoparticles (nSe) at 0, 3, and 10 mgl-1 or corresponding doses of sodium selenate (BSe). The BSe/nSe treatment at 3 mgl-1 increased shoot and root biomass, while at 10 mgl-1 moderately reduced biomass accumulation. Foliar application of BSe/nSe, especially the latter, at the lower dose enhanced fruit production, and postharvest longevity, while at the higher dose induced moderate toxicity and restricted fruit production. In leaves, the BSe/nSe treatments transcriptionally upregulated miR172 (mean = 3.5-folds). The Se treatments stimulated the expression of the bZIP transcription factor (mean = 9.7-folds). Carotene isomerase (CRTISO) gene was transcriptionally induced in both leaves and fruits of the nSe-treated seedlings by an average of 5.5 folds. Both BSe or nSe at the higher concentration increased proline concentrations, H2O2 accumulation, and lipid peroxidation levels, suggesting oxidative stress and impaired membrane integrity. Both BSe or nSe treatments also led to the induction of enzymatic antioxidants (catalase and peroxidase), an increase in concentrations of ascorbate, non-protein thiols, and soluble phenols, as well as a rise in the activity of phenylalanine ammonia-lyase enzyme. Supplementation at 3 mgl-1 improved the concentration of mineral nutrients (Mg, Fe, and Zn) in fruits. The bioaccumulated Se contents in the nSe-treated plants were much higher than the corresponding concentration of selenate, implying a higher efficacy of the nanoform towards biofortification programs. Se at 10 mgl-1, especially in selenate form, reduced both size and density of pollen grains, indicating its potential toxicity at the higher doses. This study provides novel molecular and physiological insights into the nSe efficacy for improving plant productivity, fruit quality, and fruit post-harvest longevity.

Selenium overexposure induces insulin resistance: In silico study.

BACKGROUND AND AIMS: Several studies raise concerns about the possible association of high selenium exposure with insulin resistance and type 2 diabetes. This in silico study proposes a possible mechanism of insulin resistance in the case of overexposure to selenium. METHOD: A study was carried out using molecular modeling, where cysteines of the insulin-receptor are replaced by selenocysteines. Calculation of the interaction energy of the receptor was performed in both cases with Auto Dock Tools and Vina 4.2 software to predict whether the substitution of amino acid could lead to destabilization of the protein-ligand complex and therefore possibly insulin resistance. Finally, the docked complex was analyzed by using BIOVIA Discovery Studio Visualizer to show the type of interactions between the ligands and insulin-receptor, and to determine the distance of the ligands from the binding site on insulin-receptor. RESULTS: The results show that the substitution of cysteine by selenocysteine in the insulin receptor does not lead to stabilization of the complex receptor/insulin, but to its disruption.In addition, the types and the number of bonds between insulin and its receptor in the two cases are different, where 7 strong bonds between insulin and its receptor were found in the case of the cysteine complex compared to 6 weak bonds in the second case. CONCLUSION: Findings of this study suggest that misincorporation of selenocysteines in insulin receptor could lead to destabilization of the insulin-receptor complex and therefore may possibly cause an insulin resistance.