Search

Purpose: Graves' orbitopathy (GO) is the main extrathyroidal manifestation of Graves' disease. However, limited studies have investigated the actual efficacy of selenium in GO therapy. This longitudinal study explored the effect of selenium on QOL and prognosis of patients with mild-to-moderate GO., Methods: We conducted a 5-year prospective controlled cohort clinical trial to determine the effect of selenium on 74 patients with mild-to-moderate GO. Patients received selenium yeast or placebo orally for 6 months and were followed up at 6 months and at 5 years by biochemical examination, ophthalmologist evaluation and QOL questionnaire to assess oculopathy and QOL., Results: (1) During a follow-up period of 3-6 months, in the selenium group, the symptoms of tearing, grittiness and conjunctival congestion improved (P < 0.01); clinical activity scores and total GO-QOL scores increased relative to baseline (P < 0.01); TRAb was decreased at the 6-month evaluation (P = 0.003); and patients treated with selenium had a higher rate of improvement and a lower rate of worsening than patients treated with placebo (P < 0.05). (2) Exploratory evaluations at 6 months after drug withdrawal confirmed the earlier results; further changes included alleviation of blurred vision and double vision symptoms in the selenium group (P < 0.01). (3) At the 5-year follow-up, compared with baseline, proptosis, clinical activity scores, TRAb level and total GO-QOL scores in both the selenium and placebo groups were significantly improved (P < 0.01)., Conclusion: Six months of selenium supplementation may effectively change the early course of mild-to-moderate GO, but this regimen makes no difference in long-term outcomes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Gastric ulcers are one of the most prevalent gastrointestinal disorders. The current study investigated the antioxidant and anti-inflammatory effects of selenium (Se) and lecithin (Lec) alone and in combination against ethanol-induced gastric ulcers in mice, and their ability to modulate insulin-like growth factor-1 (IGF-1)/ Phosphatase and tensin homologue deleted on chromosome 10 (PTEN)/ Protein kinase B (Akt)/ Forkhead box O3a (FoxO3a) signaling. The mice were divided into normal, ethanol, Se + ethanol, Lec + ethanol, Se + Lec + ethanol, and omeprazole + ethanol groups. Treatment with the selected doses was continued for 14 days before a single dose of absolute ethanol (5 ml/kg body weight) was administered to induce gastric ulcers in mice. The results showed that pretreatment with Se and Lec combination effectively decreased both the macro- and microscopic gastric lesions and increased the protection index compared to the ethanol group. Remarkably, the Se and Lec combination decreased the levels of reactive oxygen species, malondialdehyde, and cytochrome c and increased glutathione, glutathione peroxidase, and thioredoxin reductase activities in gastric tissues. The Se and Lec combination increased prostaglandin E2 and interleukin-10 levels but decreased tumor necrosis factor-α, interleukin-6 and interleukin-1β levels compared to either treatment alone. Interestingly, this combination decreased the expression of IGF-1, p-Akt, and FoxO3a proteins and increased PTEN expression in gastric tissues. The gastric tissues examination by hematoxylin and eosin staining confirmed these results. Therefore, the Se and Lec combination showed superior protective effects against ethanol-induced gastric ulcers in mice, compared to either treatment alone, through antioxidant, and anti-inflammatory activities, in addition to modulating IGF-1/PTEN/Akt/FoxO3a pathway signaling., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Idiopathic male infertility (IMI) remains challenging as the etiology of semen abnormalities is still unidentified. Sperm DNA fragmentation (SDF) has been suggested as a potential mechanism. Oral antioxidants including selenium have been tried for IMI with variable results. This study was undertaken to explore the effect of selenium therapy on semen parameters, antioxidant capacity, and SDF in infertile patients with idiopathic oligoasthenoteratospermia (OAT). Sixty-five infertile men with idiopathic OAT and fifty fertile controls were included in this prospective clinical study. Patients received selenium (200 μg/day) orally for 6 months. Seminal fluid parameters (WHO 5th criteria), total antioxidant capacity (TAC), catalase (CAT), and seminal SDF levels were assessed for all participants at the start of the study and after 6 months. Sperm concentration (P < 0.001), progressive motility (P < 0.001), and total motility (P < 0.01) significantly increased in patients after selenium therapy. Seminal TAC and CAT increased in patients post-therapy as compared to baseline values (P < 0.01). SDF levels significantly decreased (P < 0.001) in patients following selenium treatment in comparison to baseline values. SDF levels also correlated negatively with sperm progressive motility (r =  - 0.44, P = 0.003) and total motility (r =  - 0.48, P = 0.001). In conclusion, selenium therapy (200 μg/day) for 6 months increases sperm concentration, motility, seminal antioxidant capacity, and reduces SDF in patients with idiopathic OAT. Thus, selenium could be a promising therapy for men with IMI and may boost their fertility and fertility treatment outcomes., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Polycystic ovary syndrome (PCOS) occurs during the reproductive period in women and is characterized by reproductive, endocrine, and metabolic disorders. Androgen plays a decisive role in its pathogenesis due to the interaction between hyperandrogenism and insulin resistance, which might be improved by selenium nanoparticles (SeNPs). The present study aimed to clarify the effect of SeNPs on androgen synthesis and action in the PCOS model and the resulting effect on ovarian function. Fifty-five 7-week-old female albino rats (90-105 g) were divided equally into five groups: control (C), fed a standard diet for 11 weeks; high-fat diet (HFD) group, fed HFD for 11 weeks; HFD and letrozole (L) (HFD + L), fed HFD for 11 weeks and administrated orally with L, at a daily dose of 1 mg/kg BW, for three weeks from the 7th to 9th week of the trial; HFD + L + 0.1SeNPs and HFD + L + 0.2SeNPs groups, treated the same as HFD + L group and orally gavaged SeNPs at daily doses of 0.1 and 0.2 mg/kg BW, respectively, during the last 14 day of the experiment. Daily determination of estrous cycle was performed, and at the end of the experimental period, BMI, serum glucose, insulin, HOMA-IR, lipid profile, sex hormones, TNF-α, IL6, oxidative stress biomarkers, ovarian mRNA expression of different proteins and enzymes involved in steroidogenesis, pathological examination, and immunohistochemical staining for androgen receptor (AR) were evaluated. Treatment of SeNPs restored estrous cyclicity, decreased BMI, and insulin resistance, improved dyslipidemia, reduced serum testosterone, and improved ovarian histopathology in PCOS rats. Furthermore, the anti-inflammatory and antioxidant impacts of SeNPs were remarkably noticed. Administration of SeNPs decreased androgen synthesis and expression of ovarian AR protein by decreasing the mRNA expression of STAR, Cyp11A1, Cyp17A1, and HSD17B3 and increasing the expression of Cyp19α1. Conclusively, SeNPs decreased androgen synthesis and blocked the vicious circle initiated by excessive androgen secretion via decreased AR expression. Thus, it may effectively treat PCOS cases by eliminating its reproductive, endocrine, and metabolic dysfunctions., (© 2023. The Author(s).)

Polycystic ovarian syndrome (PCOS) is considered the most frequent gynecological endocrine disorder that causes anovulatory infertility. The current study aimed to investigate the potential significance of selenium nanoparticles (SeNPs), an IL-1 inhibitor, in the treatment of letrozole-induced PCOS in rats that satisfied the metabolic and endocrine parameters found in PCOS patients. Letrozole (2 ppm, per orally, p.o.) was given orally to female Wistar rats for 21 days to develop PCOS. After PCOS induction, rats were given SeNPs (25 ppm/day, p.o.), SeNPs (50 ppm/day, p.o.), or metformin (2 ppm/day, p.o.) for 14 days. PCOS was associated with an increase in body weight, ovarian weight, ovarian size, and cysts, as well as an increase in blood testosterone, luteinizing hormone (LH), and insulin, glycaemia, and lipid profile levels. The SeNP administration decreased all of these variables. Furthermore, SeNPs significantly reduced letrozole-induced oxidative stress in the ovaries, muscles, and liver by decreasing elevated levels of malondialdehyde and total nitrite while raising suppressed levels of superoxide dismutase and catalase. SeNPs increased the amounts of the protective proteins Kelch-like ECH-associated protein 1 (Keap-1), nuclear factor erythroid 2-related factor 2 (Nrf2), and OH-1. It was depicted from the study that SeNPs reduce the upregulation of inflammatory cytokines that are interleukin 6 (IL-6), tumour necrosis factor α (TNF-α), and the interleukin 1 (IL-1). Our findings show that SeNPs, through their antioxidant and anti-inflammatory characteristics, alleviate letrozole-induced PCOS., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This work investigated the impact of vitamin K2 and selenium co-supplementation on metabolic profile and indicators of cardiovascular health in dyslipidemic rabbits. Fifty adult male rabbits were equally allocated into 5 groups: Control group, Dyslipidemic group: received 0.5% cholesterol in diet for 12 weeks, groups 3, 4 and 5 dyslipidemic rabbits daily treated with vitamin K2 (10 mg/kg bw) or/and selenium (1 mg/kg bw) for 8 weeks. Co-supplementation of vitamin K2 and selenium significantly decreased body weight gain and blood pressure elevation in dyslipidemic rabbits compared to un-treated ones. Consuming vitamin K2 plus selenium also markedly lowered serum lipids encompassing cholesterol, triglycerides and LDL and elevated HDL relative to placebo. Additionally, such co-supplementation reduced fasting glucose and insulin, enhancing insulin sensitivity with respect to placebo. Regarding cardiovascular risk markers, dyslipidemic rabbits received vitamin K2 concurrently with selenium displayed lower levels of atherogenic index (LDL/HDL), serum C-reactive protein, heart fatty acid-binding protein and asymmetric dimethylarginine as well as aortic ox-LDL, lipid peroxidation and calcium but higher levels of serum nitric oxide and aortic total antioxidants than un-treated ones. Concomitant administration of vitamin K2 and selenium improved metabolic profile, markers of cardiovascular health and atherosclerosis in dyslipidemic rabbits., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Selenium (Se) is an essential micronutrient with several functions in cellular and molecular anticancer processes. There is evidence that Se depending on its chemical form and the dosage use could act as a modulator in some anticancer mechanisms. However, the metabolism of organic and inorganic forms of dietary selenium converges on the main pathways. Different selenocompounds have been reported to have crucial roles as chemopreventive agents, such as antioxidant activity, activation of apoptotic pathways, selective cytotoxicity, antiangiogenic effect, and cell cycle modulation. Nowadays, great interest has arisen to find therapies that could enhance the antitumor effects of different Se sources. Herein, different studies are reported related to the effects of combinatorial therapies, where Se is used in combination with proteins, polysaccharides, chemotherapeutic agents or as nanoparticles. Another important factor is the presence of single nucleotide polymorphisms in genes related to Se metabolism or selenoprotein synthesis which could prevent cancer. These studies and mechanisms show promising results in cancer therapies. This review aims to compile studies that have demonstrated the anticancer effects of Se at molecular levels and its potential to be used as chemopreventive and in cancer treatment., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Data on the effects of selenium (Se) supplementation on clinical outcomes, metabolic profiles, and pulsatility index (PI) in high-risk mothers in terms of preeclampsia (PE) screening with quadruple tests are scarce. This study evaluated the effects of Se supplementation on clinical outcomes, metabolic profiles, and uterine artery PI on Doppler ultrasound in high-risk mothers in terms of PE screening with quad marker. The current randomized, double-blind, placebo-controlled trial was conducted among 60 high-risk pregnant women screening for PE with quad tests. Participants were randomly allocated into two groups (30 participants each group), received either 200 µg/day Se supplements (as Se amino acid chelate) or placebo from 16 to 18 weeks of pregnancy for 12 weeks. Clinical outcomes, metabolic profiles, and uterine artery PI were assessed at baseline and at the end of trial. Se supplementation resulted in a significant elevation in serum Se levels (β 22.25 µg/dl; 95% CI, 18.3, 26.1; P < 0.001) compared with the placebo. Also, Se supplementation resulted in a significant elevation in total antioxidant capacity (β 82.88 mmol/L; 95% CI, 3.03, 162.73; P = 0.04), and total glutathione (β 71.35 µmol/L; 95% CI, 5.76, 136.94; P = 0.03), and a significant reduction in high-sensitivity C-reactive protein levels (β - 1.52; 95% CI, - 2.91, - 0.14; P = 0.03) compared with the placebo. Additionally, Se supplementation significantly decreased PI of the uterine artery in Doppler ultrasound (β - 0.09; 95% CI, - 0.14, - 0.04; P = 0.04), and a significant improvement in depression (β - 5.63; 95% CI, - 6.97, - 4.28; P < 0.001), anxiety (β - 1.99; 95% CI, - 2.56, - 1.42; P < 0.001), and sleep quality (β - 1.97; 95% CI, - 2.47, - 1.46; P < 0.001). Se supplementation for 12 weeks in high-risk pregnant women in terms of PE screening with quad marker had beneficial effects on serum Se level, some metabolic profiles, uterine artery PI, and mental health. IRCT Registration: htpp:// www.irct.ir ; identifier IRCT20200608047701N1., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The rapid spread of new pathogens (SARS-CoV-2 virus) that negatively affect the human body has huge consequences for the global public health system and the development of the global economy. Appropriate implementation of new safety regulations will improve the functioning of the current model supervising the inhibition of the spread of COVID-19 disease. Compliance with all these standards will have a key impact on the health behavior of individual social groups. There have been demonstrably effective treatments that proved to be effective but were rapidly dismissed for unknown reasons, such as ivermectin and hydroxychloroquine. Various measures are used in the world to help inhibit its development. The properties of this element provide hope in preventing the development of the SARS-CoV-2 virus. The aim of this review is to synthesize the latest literature data and to present the effect of sodium selenite in reducing the incidence of COVID-19 disease., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Alzheimer's disease (AD) is a brain disorder associated with a gradual weakening in neurocognitive functions, neuroinflammation, and impaired signaling pathways. Resveratrol (RSV) has neuroprotective properties, but with low bioavailability, and low solubility in vivo. Selenium (Se) is an essential micronutrient for brain function. Thus, this study aimed to evaluate the role of formulated RSV-Se nanoparticles (RSV-SeNPs) on neurochemical and histopathological approaches associated with the AD model in rats induced by Aluminum chloride (AlCl 3 ) at a dose of 100 mg/kg/day for 60 days. RSV-SeNPs supplementation attenuates the impaired oxidative markers and mitochondrial dysfunction. The ameliorative effect of RSV-SeNPs on cholinergic deficits was associated with clearance of amyloid β (Aβ). Furthermore, activation of phosphatidylinositol 3 kinase (PI3K) deactivates glycogen synthase kinase 3 beta (GSK-3β)-mediated tau hyperphosphorylation. Additionally, RSV-SeNPs downregulate signal transducer and activator of transcription (STAT3) expression as well as interleukin-1β (IL-1β) levels, therefore alleviating neuroinflammation in AD. Moreover, RSV-SeNPs upregulate the expression of Sirtuin-1 (SIRT1) and lower that of microRNA-134, consequently increasing neurite outgrowth. Eventually, the obtained results showed that nano-formulation of resveratrol with selenium maximized the therapeutic potential of RSV against Alzheimer's disease not only by their antioxidant but also by anti-inflammatory effect improving the neurocognitive function and modulating the signaling pathways., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Selenium, an essential trace element for human health, exerts an indispensable effect in maintaining physiological homeostasis and functions in the body. Selenium deficiency is associated with arthropathies, such as Kashin-Beck disease, rheumatoid arthritis, osteoarthritis, and osteoporosis. Selenium deficiency mainly affects the normal physiological state of bone and cartilage through oxidative stress reaction and immune reaction. This review aims to explore the role of selenium deficiency and its mechanisms existed in the pathogenesis of arthropathies. Meanwhile, this review also summarized various experiments to highlight the crucial functions of selenium in maintaining the homeostasis of bone and cartilage., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: This study critically reappraises the documentation on the clinical efficacy of selenium supplementation in chronic autoimmune thyroiditis (AIT) with the goal of improving the normalization of the treatment of this disease., Methods: A literature search was performed in the Medline, Embase, and Cochrane Library databases. Twenty-three trials conducted in adults with AIT comparing the efficacy of selenium with or without levothyroxine (LT4) versus placebo and/or LT4 were eligible. The assessed outcomes were primarily pooled using a random- or fixed effects model based on the results of the heterogeneity test. The quality of evidence was assessed per outcome., Results: In LT4-treated populations, patients receiving selenium demonstrated lower thyroid peroxidase antibody (TPOAb) levels at 3 months (mean difference [MD], -236.88; 95% confidence interval [CI], -353.35 to -120.41; p < 0.0001), 6 months (MD, -407.17; 95% CI, -623.60 to -190.73; p = 0.0002), and 12 months (MD, -327.03; 95% CI, -613.78 to -40.28; p = 0.0254), while thyroglobulin antibody (TgAb) levels only decreased at 12 months. In non-LT4-treated population, the selenium group demonstrated significantly lower TPOAb levels after 3 months (MD, -203.07; 95% CI, -395.44 to -10.70; p = 0.0385) and 6 months (MD, -322.27; 95% CI, -597.50 to -47.04; p = 0.0217) but not after 12 months, while TgAb levels only decreased at 3 months. There was no significant change in thyroid stimulating hormone (TSH) levels. Lower thyroid echogenicity was observed in all patients receiving selenium at 3, 6, and 12 months. However, these participants had a significantly higher risk of reported adverse effects., Conclusions: Current evidence does not justify the emerging use of selenium supplementation in the treatment of AIT, despite it resulting in a decrease in autoantibody levels.

The purpose of this study was to evaluate the neuroprotective effect of local implantation of a controlled delivery system of chitosan hydrogel loaded with selenium nanoparticles in rats with spinal cord injury (SCI). For this purpose, 60 adult female rats were randomly divided into three equal groups. In all three groups, SCI was induced by aneurysm clamping at the level of thoracic vertebrae under inhaled anesthesia with isoflurane. In one group after spinal cord injury, chitosan hydrogels loaded with selenium nanoparticles (treatment group), and in the other group, only chitosan hydrogels (positive control group) were placed at the site of injury. In the last group (negative control), no material was placed in the injury site. Hematoxylin-eosin and glial fibrillary acidic protein (GFAP) staining evaluated histological changes at the site of injury on days 3, 7, 21, and 28 after surgery. Evaluations show that hemorrhage and inflammation also have a marked decrease in inflammatory cells at different times in the treatment group. This decrease was also seen in the chitosan group but was less severe than in the treatment group. The formation of nerve fibers was also observed in the treatment group over time of injury. Immunohistochemical studies of damaged tissue showed higher expression of GFAP protein in the astrocytes of the treatment group than in the other two groups and the chitosan group compared with the negative control group. A controlled drug delivery system containing selenium nanoparticles seems to play a role in the protection of nerve cells through its anti-inflammatory effect.

Oxidative stress (OS) is a key contributing factor in 30-80% of male infertility cases. To date, several antioxidant treatments have been put forth to manage OS-induced male infertility. This study intended to elucidate the impact of coenzyme Q10 (CoQ10) and selenium on seminal fluid parameters and antioxidant status in infertile men with idiopathic oligoasthenoteratospermia (OAT). In this prospective study, 70 patients with idiopathic OAT were randomly allocated to receive CoQ10 (200 mg/day) or selenium (200 μg/day) for 3 months. Semen quality parameters (following WHO guidelines, 5th edition), total antioxidant capacity (TAC), catalase (CAT), and superoxide dismutase (SOD) activities were compared before and after the treatment. The results of the study showed an increase in sperm concentration with CoQ10 treatment (p < 0.01) as well as increased progressive sperm motility (p < 0.01 and p < 0.05) and total sperm motility (p < 0.01 and p < 0.05) with CoQ10 and selenium treatment respectively. There was also a significant improvement in TAC (p < 0.01 and p < 0.05) and SOD (p < 0.01 and p < 0.05) following treatment with CoQ10 and selenium respectively while CAT improved only with CoQ10 therapy (p < 0.05). Sperm concentration, motility, and morphology also correlated significantly with TAC, SOD, and CAT (r = 0.37-0.76). In conclusion, treatment with CoQ10 (200 mg) or selenium (200 μg) could improve sperm concentration, motility, and antioxidant status in infertile men with idiopathic OAT with CoQ10 providing the higher improvement.

Polycystic ovary syndrome (PCOS) is characterized by various reproductive and cardiometabolic disorders. Asymmetric dimethylarginine (ADMA) is associated with cardiovascular, metabolic, and hormonal status. Selenium, a micronutrient with antioxidant properties, could affect multiple physiological pathways. This study aimed to investigate the effect of selenium supplementation on ADMA, cardiometabolic risk factors, and hormonal status in women with PCOS. In this randomized, double-blind, placebo-controlled clinical trial, 66 women with PCOS, aged 18-45 years, were randomly assigned to receive either 200 μg/day selenium or placebo, for 12 weeks. Circulating concentrations of ADMA, testosterone, sex hormone-binding globulin (SHBG), lipid profiles, and glycemic parameters were assessed at baseline and following supplementation. ADMA concentration decreased significantly compared to baseline values (85.14 ± 75 to 56.4 ± 38.64 ng/l, p = 0.02) in the selenium group. This change was marginally significant compared with the placebo group (28.74 ± 68.63 vs. - 1.77 ± 52.88 ng/l, p = 0.056). Serum testosterone levels declined significantly in the intervention compared to the placebo group (0.01 ± 0.17 vs. - 0.08 ± 0.18 ng/ml, p = 0.038). Pre- to post-Apo-B100/Apo-A1 ratio declined considerably in the intervention group (0.72 ± 0.16 to 0.65 ± 0.16, p = 0.003). No further differences were observed in SHBG, lipid profiles, Apo-A1, Apo-B100, Apo-B100/Apo-A1 ratio, and glycemic control between the two groups at the end of the study. Selenium supplementation for 12 weeks had beneficial effects on reduction of circulating ADMA and total testosterone levels in women with PCOS. No significant improvements were seen in other cardiometabolic risk factors. The effects of selenium supplementation on hormonal, reproductive, and cardiometabolic disorders, considering the potential mediating role of ADMA, should be further investigated.

The present study aims to evaluate the efficacy of selenium (Se) alone or combined with carbamazepine (CBZ) against the adverse effects induced by the chemoconvulsant pentylenetetrazole (PTZ) in the cortex of adult male rats. Electrocorticogram (ECoG) and oxidative stress markers were implemented to evaluate the differences between treated and untreated animals. Animals were divided into five groups: control group that received i.p. saline injection, PTZ-treated group that received a single i.p. injection of PTZ (60 mg/kg) for induction of seizures followed by a daily i.p. injection of saline, Se-treated group that received an i.p. injection of sodium selenite (0.3 mg/kg/day) after PTZ administration, CBZ-treated group that received orally CBZ (80 mg/kg/day) after PTZ administration, and combination (Se plus CBZ)-treated group that received an oral administration of CBZ (80 mg/kg/day) followed by an i.p. injection of sodium selenite (0.3 mg/kg/day) after PTZ administration. Quantitative analyses of the ECoG indices and the neurochemical parameters revealed that Se and CBZ have mitigated the adverse effects induced by PTZ. The main results were decrease in the number of epileptic spikes, restoring the normal distribution of slow and fast ECoG frequencies and attenuation of most of the oxidative stress markers. However, there was an increase in lipid perioxidation marker in combined treatment of CBZ and Se. The electrophysiological and neurochemical data proved the potential of these techniques in evaluating the treatment's efficiency and suggest that supplementation of Se with antiepileptic drugs (AEDs) may be beneficial in ameliorating most of the alterations induced in the brain as a result of seizure insults and could be recommended as an adjunct therapy with AEDs.

To investigate selenium (Se) concentrations in serum of patients with rheumatoid arthritis (RA), osteoarthritis (OA), and Kashin-Beck disease (KBD), together with the effect of Se supplement (chondroitin sulfate [CS] nano-Se [SeCS]) on CS structure-modifying sulfotransferases in KBD chondrocyte. Fifty serum samples from each group with aged-matched (40-60 years), normal control (N), RA, OA, and KBD (25 males and females, respectively) were collected to determine Se concentrations. Furthermore, the KBD chondrocytes were divided into two groups following the intervention for 24 h: (a) non-treated KBD group and (b) SeCS-treated KBD group (100 ng/mL SeCS). The ultrastructural changes in chondrocytes were observed by transmission electron microscopy (TEM). Live/dead staining was used to observe cell viability. The expression of CS-modifying sulfotransferases including carbohydrate sulfotransferase 12, 13, and 15 (CHST-12, CHST-13, and CHST-15, respectively), and uronyl 2-O-sulfotransferase (UST) were examined by quantitative real-time polymerase chain reaction and western blotting analysis after SeCS intervention. The Se concentrations in serum of KBD, OA, and RA patients were lower than those in control. In OA, RA, and control, Se concentrations were higher in male than in female, while it is opposite in KBD. In the cell experiment, cell survival rate and mitochondrial density were increased in SeCS-treated KBD groups. Expressions of CHST-15, or CHST-12, and CHST-15 on the mRNA or protein level were significantly increased. Expression of UST slightly increased on the mRNA level, but no change was visible on the protein level. Se deficiency in serum of RA, OA, and KBD was observed. SeCS supplemented in KBD chondrocytes improved their survival rate, ameliorated their ultrastructure, and increased the expression of CS structure-modifying sulfotransferases.

Arsenic (As) and cadmium (Cd) are elements arousing major public health concerns associated with environmental pollution, high toxicity potential, and carcinogenic nature. However, selenium (Se) at low doses and incorporated into enzymes and proteins has antioxidant properties and protects animals and humans from the risk of various diseases. It also has an exceptionally narrow range between necessary and toxic concentrations, which is a well-known hindrance in its use as a dietary supplement. The present article aims to update and expand the role of Se in As and Cd toxicity discussed in our earlier paper. In general, recent reports show that Se, regardless of its form (as selenite, selenomethionine, nanoSe, or Se from lentils), can reduce As- or Cd-mediated toxicity in the liver, kidney, spleen, brain, or heart in animal models and in cell culture studies. As was suggested in our earlier review, Se antagonizes the toxicity of As and Cd mainly through sequestration of these elements into biologically inert complexes and/or through the action of Se-dependent antioxidant enzymes. An increase in the As methylation efficiency is proposed as a possible mechanism by which Se can reduce As toxicity. However, new studies indicate that Se may also diminish As or Cd toxicity by activation of the Nrf2 pathway. In addition, this paper discusses possible signs of Se toxic effects, which may be a challenge for its future use in the therapy of As and Cd poisoning and provide future directions to address this issue.

Purpose: Selenium is frequently in nutraceuticals for pregnancy, given its role on fertility and thyroid metabolism. However, most evidence rise from non-controlled studies. We aimed to evaluate the protective effect of selenium against thyroid autoimmunity during and after pregnancy., Methods: A multicenter, randomized, double-blind, placebo-controlled trial was performed and promoted by the Young Italian Endocrinologists Group (EnGioI)-Italian Society of Endocrinology. Forty-five women with thyroiditis in pregnancy were enrolled and randomly assigned to L-selenomethionine (L-Se-Met) 83 mcg/day or placebo (PLB) and evaluated at 10 ± 2 (T1), 36 ± 2 weeks of gestation (T2) and 6 months after delivery (postpartum, PP)., Results: We measured a significant reduction of autoantibodies after pregnancy in L-Se-Met group [at PP: TgAb 19.86 (11.59-52.60), p < 0.01; TPOAb 255.00 (79.00-292.00), p < 0.01], and an antibodies titer's rebound in PLB group (TgAb 151.03 ± 182.9, p < 0.01; TPOAb 441.28 ± 512.18, p < 0.01). A significant increase in selenemia was measured in L-Se-Met group at T2 (91.33 ± 25.49; p < 0.01) and PP (93.55 ± 23.53; p = 0.02). Two miscarriage occurred in PLB. No differences were found in thyroid volume, echogenicity, quality of life, maternal/fetal complications., Conclusions: SERENA study demonstrated a beneficial effect of L-Se-Met supplementation on autoantibody titer during pregnancy and on postpartum thyroiditis recurrence.

This study was carried out to evaluate the effects of selenium supplementation on glycemic control, lipid profiles, and biomarkers of inflammation and oxidative stress in patients undergoing for coronary artery bypass grafting (CABG) surgery. This randomized, double-blind, placebo-controlled trial was performed among 33 patients undergoing for CABG surgery, aged 40-85 years old. Subjects were randomly allocated into two groups to intake either 200 μg/day selenium supplements as selenium yeast (n = 17) or placebo (n = 16) for 4 weeks. Glycemic control, lipid profiles, and biomarkers of inflammation and oxidative stress were assessed at baseline and at the end of trial. After the 4-week intervention, selenium supplementation significantly decreased fasting plasma glucose (FPG) (β, 6.76 mg/dL; 95% CI, - 13.13, - 0.40; P = 0.03), insulin (β, - 1.14 μIU/mL; 95% CI, - 2.01, - 0.28; P = 0.01); homeostasis model of assessment-estimated insulin resistance (HOMA-IR) (β - 0.35; 95% CI, - 0.62, - 0.08; P = 0.01); and total-/HDL-cholesterol ratio (β - 0.31; 95% CI, - 0.51, - 0.09; P = 0.008); and significantly increased HDL-cholesterol levels (β, 2.72 mg/dL; 95% CI, 0.89, 4.55; P = 0.005) compared with the placebo. Moreover, selenium supplementation led to a significant reduction in high-sensitivity C-reactive protein (hs-CRP) (β, - 0.68 mg/L; 95% CI, - 1.18, - 0.17; P = 0.01) and malondialdehyde (MDA) (β, - 0.27 μmol/L; 95% CI, - 0.47, - 0.07; P = 0.009), and a significant elevation in total glutathione (GSH) levels (β, 77.33 μmol/L; 95% CI, 56.11, 98.55; P < 0.001) compared with the placebo. Selenium supplementation did not affect other metabolic profiles. Overall, our study demonstrated that selenium supplementation for 4 weeks to patients undergoing for CABG surgery had beneficial effects on FPG, insulin, HOMA-IR, total-/HDL-cholesterol ratio, HDL-cholesterol, hs-CRP, GSH, and MDA levels, but did not affect other metabolic profiles. Clinical trial registration number: http://www.irct.ir : IRCT2017090533941N22.

Aflatoxin B1 (AFB 1 ) is the most toxic among the mycotoxins and causes detrimental health effects on the liver of human and animals. Selenium (Se) plays an important role in protection of various animal species against numerous notorious toxic agents. The present study is designed to explore the protective effects of Se against AFB 1 -induced liver pathogenesis by the methods of histopathology, flow cytometry, quantitative real-time polymerase chain reaction (qRT-PCR), and biochemical analysis. A total of 312, 1-day-old healthy Cobb-500 broilers were randomly divided into four groups and fed with basal diet (control group), 0.6 mg/kg AFB 1 (AFB 1 group), 0.4 mg/kg Se (+ Se group), and 0.6 mg/kg AFB 1  + 0.4 mg/kg Se (AFB 1 + Se group) for 21 days, respectively. Our results showed that 0.4 mg/kg Se supplement in broiler's diets could alleviate the AFB 1 -induced histological lesions in the liver. The apoptosis analysis by flow cytometry showed that 0.4 mg/kg Se ameliorated the AFB 1 -induced apoptosis in the liver. Moreover, the mRNA expression levels of Fas, TNF-α, FAS-associated death domain, TNF receptor-associated death domain, TNF receptor-associated factor 2, caspase 10, caspase 8, B cell lymphoma 2, IκB kinase, X-linked inhibitor of apoptosis protein, caspase 9, and caspase 3 analyzed by qRT-PCR demonstrated that 0.4 mg/kg Se could relieve the impact caused by AFB 1 to these parameters. The biochemical analyses of activities of CAT, GSH-Px and SOD, hydroxyl ion scavenging and contents of MDA and GSH in liver cells also indicated that 0.4 mg/kg Se has positive effect on AFB 1 -induced oxidative stress in the liver. In conclusion, Se could relieve AFB 1 -induced apoptosis by the molecular regulation of death receptors pathway in the liver of broilers. The outcomes from the present study may lead to a better understanding of the nature of selenium's essentiality and its protective roles against AFB 1 .

Selenium (Se), an essential trace element and potent nutritional antioxidant, exerts its biological effects through incorporation into selenoproteins like glutathione peroxidase (GPx). Modest decrement in the levels of GPx could be partly responsible for peroxidation of RBCs, which results into hemolytic anemia. Therefore, it is hypothesized that dietary Se, as selenoproteins (GPx), can maintain the homeostasis in RBCs and regulate the erythropoiesis by preventing oxidative stress-mediated hemolysis. Se-deficient (0.01 ppm), Se-adequate (0.1 ppm sodium selenite), and Se-supplemented (0.5 ppm sodium selenite) status were created in Balb/c mice by feeding yeast-based diets for 8 weeks and established by measuring Se levels in plasma and activities, expressions of Se-dependent selenoproteins. Fifty percent of mice from each differential Se group were treated with phenylhydrazine (PHZ, 20 mg/kg, i.p.) to induce hemolytic anemia. Results indicated that PHZ-treated Se-deficient animals demonstrated increased hemolysis, abnormal RBC morphology, increase in Heinz bodies and reticulocytes, and denaturation of hemoglobin to globin precipitates and methemoglobin. Se supplementation protected against these hemolytic changes and makes RBCs less fragile. These findings were consistent with dietary Se concentration-dependent changes in activity and expression of GPx indicating that ROS-mediated oxidative stress is integral to hemolysis. Protective effects of Se supplementation against increased levels of ROS, protein carbonyls, and peroxide damage to membrane lipids and enzymatic antioxidants validated these observations. In conclusion, dietary Se supplementation protected the RBCs against hemolysis by mitigating ROS-mediated oxidative stress.

Colloidal selenium, was first used to treat cancer as early as 1911 in both humans and mice. Selenium was identified as the toxic component in forage plants of sheep, cattle, and horses in the 1930s. The animal toxicity of selenium compounds was determined to be from the metabolism by animals of the elevated concentrations of Se-methylselenocysteine and selenomethionine in plants. The metabolism of both Se-methylselenocysteine and selenomethionine by animals gives rise to the metabolite, methylselenide (CH 3 Se-), which if in sufficient concentration oxidizes thiols and generates superoxide and other reactive oxygen species. Cancer cells that may overly express methionine gamma-lyase, or beta-lyase (methioninase), by induced viral genomic expression, are susceptible to free radical-induced apoptosis from selenomethionine or Se-methylselenocysteine supplementation.

Selenium is known to be a neuroprotective agent in respect to a number of neuronal diseases and pain. The aim of this study was to evaluate the neuroprotective effect of the oral administration of selenium nanoparticles in rats with spinal cord injury (SCI). Forty adult female rats were randomly assigned to two equal groups as experimental and control. Under general inhalation anesthesia, in both groups, SCI was created, at the T9-10 level of the column. On the third day after the operation, a supplement of selenium nanoparticle was administered to the experimental group at 0.2 mg/kg per day. The histology of the site of injury, IGF-1 serum concentrations, and changes in the white blood cells were examined in both groups at different pre-surgical and post-surgical times. The results of the current study showed a significant decrease in the total white blood cells, including lymphocyte, neutrophil, and monocyte in the experimental group compared to the control group. Histological evaluation showed that the inflammatory responses reduced significantly in the experimental group compared to the control group. In conclusion, we speculate that the decrease in the number of inflammatory cells after oral administration of the selenium nanoparticles is due to the neuroprotective effects of this nanoparticle.

Aflatoxin B 1 (AFB 1 ) is a naturally occurring secondary metabolites of Aspergillus flavus and Aspergillus parasiticus, and is the most toxic form of aflatoxins. Selenium (Se) with antioxidant and detoxification functions is one of the essential trace elements for human beings and animals. This study aims to evaluate the protective effects of Se on AFB 1 -induced tissue damage and cell cycle arrest in bursa of Fabricius (BF) of chickens. The results showed that a dietary supplement of 0.4 mg·kg -1 Se alleviated the histological lesions induced by AFB 1 , as demonstrated by decreasing vacuoles and nuclear debris, and relieving oxidative stress. Furthermore, flow cytometry studies showed that a Se supplement protected AFB 1 -induced G 2 M phase arrest at 7 days and G 0 G 1 phase arrest at 14 and 21 days. Moreover, the mRNA expression results of ATM, Chk2, p53, p21, cdc25, PCNA, cyclin D 1 , cyclin E 1 , cyclin B 3 , CDK6, CDK2, and cdc2 indicated that Se supplement could restore these parameters to be close to those in the control group. It is concluded that a dietary supplement of 0.4 mg kg -1 Se could diminish AFB 1 -induced immune toxicity in chicken's BF by alleviating oxidative damage and cell cycle arrest through an ATM-Chk2-cdc25 route and the ATM-Chk2-p21 pathway.

Colorectal cancer is one of the most common causes of mortality in the world while malnutrition is responsible for one third of the problem. Selenium has been recommended for prevention of colorectal cancer. The present study was conducted to investigate the effect of selenium-enriched Saccharomyces cerevisiae in reducing colorectal cancer progression in rats. Five groups of 170-200-g weight rats (n = 40) including healthy and cancer controls, Saccharomyces cerevisiae, selenium, and selenium-enriched Saccharomyces cerevisiae-treated groups were examined. All animals except healthy control group received 40 mg 1,2-dimethylhydrazine (DMH) per kilogram weight of rat twice a week. The healthy group received normal saline, and synchronously, selenium group received soluble selenium (4 mg/mL), Saccharomyces cerevisiae and selenium-enriched groups received yeast with the density of 5 × 10 8  CFU/mL by daily gavage. All treatments were carried out for 5 weeks after the last injection. Animals were autopsied, and aberrant crypt foci (ACF) of ejected colon were studied in the 40th week. Microscopic sections were prepared for hematoxylin and eosin. Furthermore, immunohistochemical staining of CD31, BCL2, and P53 antibodies was performed. Macroscopic and microscopic evaluations showed that DMH had the least destructive effect in selenium-enriched Saccharomyces cerevisiae group compared to other groups. Selenium-enriched Saccharomyces cerevisiae reduces colorectal cancer progression by various mechanisms such as reduction in the number and size of ACF and alteration in the function of the proteins such as P53, BCL2, and CD31.

Deoxynivalenol (DON) is a mycotoxin that causes immunosuppression, especially in swine. Selenium (Se) is essential for proper functioning of the immune system in animals. However, little is known about the effects of DON and Se on cytokine or immunoglobulin production in piglets. Here, we addressed this gap by examining piglet splenic lymphocyte responses in vitro. Cells were stimulated with concanavalin A, a T cell stimulatory lectin, in the absence or presence of DON (0.1, 0.2, 0.4, and 0.8 μg/mL), Se (Na 2 SeO 3 , 2 μM), or combinations of Se 2 μM and DON 0.1-0.8 μg/mL for 12, 24, or 48 h. At each time point, supernatants and cells were collected and the expression of cytokine and immunoglobulin protein and mRNA was examined. Compared with control and Se-alone treatments, DON exposure significantly and dose dependently decreased the expression levels of IL-2, IL-4, IL-6, IL-10, IFN-γ, IgG, and IgM mRNA and protein. By contrast, co-treatment with DON + Se significantly increased the mRNA and protein levels of all factors examined, except IL-4 and IL-6, compared with DON treatment alone. The results of this investigation demonstrate that Se has the potential to counteract DON-induced immunosuppression in piglets and is a promising treatment for DON-mediated toxicity.

This study was conducted to evaluate the effects of selenium supplementation on gene expression related to insulin and lipid in infertile women with polycystic ovary syndrome (PCOS) candidate for in vitro fertilization (IVF). This randomized double-blind, placebo-controlled trial was conducted among 40 infertile women with PCOS candidate for IVF. Subjects were randomly allocated into two groups to intake either 200-μg selenium (n = 20) or placebo (n = 20) per day for 8 weeks. Gene expression levels related to insulin and lipid were quantified in lymphocytes of women with PCOS candidate for IVF with RT-PCR method. Results of RT-PCR demonstrated that after the 8-week intervention, compared with the placebo, selenium supplementation upregulated gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) (1.06 ± 0.15-fold increase vs. 0.94 ± 0.18-fold reduction, P = 0.02) and glucose transporter 1 (GLUT-1) (1.07 ± 0.20-fold increase vs. 0.87 ± 0.18-fold reduction, P = 0.003) in lymphocytes of women with PCOS candidate for IVF. In addition, compared with the placebo, selenium supplementation downregulated gene expression of low-density lipoprotein receptor (LDLR) (0.88 ± 0.17-fold reduction vs. 1.05 ± 0.22-fold increase, P = 0.01) in lymphocytes of women with PCOS candidate for IVF. We did not observe any significant effect of selenium supplementation on gene expression levels of lipoprotein(a) [LP(a)] in lymphocytes of women with PCOS candidate for IVF. Overall, selenium supplementation for 8 weeks in lymphocytes of women with infertile PCOS candidate for IVF significantly increased gene expression levels of PPAR-γ and GLUT-1 and significantly decreased gene expression levels of LDLR, but did not affect LP(a)., Clinical Trial Registration Number: http://www.irct.ir : IRCT201704245623N113.

Overall nutritional status has been proved associated with people's health. The overall nutritional status of children in Kashin-Beck disease (KBD) areas has been overlooked for decades. Therefore, it is worth investigating in the current generation to gather evidence and make suggestions for improvement. A cross-sectional study with three 24-h dietary recalls was conducted to collect raw data on the daily food intake of children. Recorded food was converted into daily nutrient intakes using CDGSS 3.0 software. WHO AnthroPlus software was used to analyse the BMI-for-age z-score (BAZ) for estimating the overall nutrition status of children. All the comparisons and regression analyses were conducted with SPSS 18.0 software. Multiple nutrient intakes among children from the Se-supplemented KBD-endemic were under the estimated average requirement. The protein-to-carbohydrate ratio (P/C ratio) was significantly higher in children from the non-Se-supplemented KBD-endemic area than the other areas (P < 0.001). The children's BAZ was negatively associated with age (B = -0.095, P < 0.001) and the number of KBD relatives (B = -0.277, P = 0.04), and it was positively associated with better housing conditions, receiving colostrum, and daily intakes of niacin and zinc by multivariate regression analysis (F = 10.337, R = 0.609, P < 0.001).Compared to non-Se-supplemented KBD-endemic area and non-endemic areas, children in Se-supplemented KBD-endemic areas have an insufficient intake of multiple nutrients. School breakfast and lunch programmes are recommended, and strict implementation is the key to ensuring a positive effect.

Aflatoxins have been considered as one of the major risk factors of male infertility, and aflatoxin B1 (AFB1) is the most highly toxic and prevalent member of the aflatoxins family. Selenium (Se), an essential nutritional trace mineral for normal testicular development and male fertility, has received extensive intensive on protective effects of male reproductive system due to its potential antioxidant and activating testosterone synthesis. To investigate the protective effect of Se on AFB1-induced testicular toxicity, the mice were orally administered with AFB1 (0.75 mg/kg) and Se (0.2 mg/kg or 0.4 mg/kg) for 45 days. We found that that Se elevated testes index, sperm functional parameters (concentration, malformation, and motility), and the level of serum testosterone in AFB1-exposed mice. Moreover, our results showed that Se attenuated the AFB1-induced oxidative stress and the reduction of testicular testosterone synthesis enzyme protein expression such as steroidogenic acute regulatory protein (StAR), P450 side-chain cleavage (P450scc), and 17β-hydroxysteroid dehydrogenase (17β-HSD) in AFB1-exposed mice. These results demonstrated that Se conferred protection against AFB1-induced testicular toxicity and can be attributed to its antioxidant and increased testosterone level by stimulating protein expression of StAR and testosterone synthetic enzymes.

Among many challenges, exposure to aflatoxins, particularly aflatoxin B 1 (AFB 1 ), is one of the major concerns in poultry industry. AFB 1 intoxication results in decreased meat/egg production, hepatotoxicity, nephrotoxicity, disturbance in gastrointestinal tract (GIT) and reproduction, immune suppression, and increased disease susceptibility. Selenium (Se) and zinc (Zn), in dietary supplementation, offer easy, cost-effective, and efficient ways to neutralize the toxic effect of AFB 1 . In the current review, we discussed the impact of AFB 1 on poultry industry, its biotransformation, and organ-specific noxious effects, along with the action mechanism of AFB 1 -induced toxicity. Moreover, we explained the biological and detoxifying roles of Se and Zn in avian species as well as the protection mechanism of these two trace elements. Ultimately, we discussed the use of Se and Zn supplementation against AFB 1 -induced toxicity in poultry birds.

This research was delineated to explore the efficacy of selenium nanoparticles delivered in liposomes (L-Se) in the mitigation of type-2 diabetes mellitus. Adult female Wistar rats were assigned into four groups: group I, the normal control group in which the rats received normal saline solution orally; group II, the diabetic control group in which the rats were injected intraperitoneally with a single dose of streptozotocin (STZ) for induction of diabetes; group III, the metformin (Met)-treated group in which the diabetic rats were treated orally with Met; and group IV, the L-Se-treated group in which the diabetic rats were treated orally with L-Se. All treatments were delivered for 21 days. Blood and pancreas tissue samples were obtained for biochemical analysis, immunohistochemical examinations, and histopathological investigation. The L-Se-treated group showed significant drop in serum glucose and pancreatic malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor-α (TNF-α), and prostaglandin F2α (PGF2α) levels associated with significant rise in serum insulin and pancreatic glutathione, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) values, in addition to significant improvement in the immunohistochemical indices (insulin and glucagon). Aforementioned results are appreciated by the histopathological findings of pancreatic tissue. In conclusion, our data have brought about compelling evidence favoring the antidiabetic potency of elemental selenium nanoparticles delivered in liposomes through preservation of pancreatic β cell integrity with consequent increment of insulin secretion and in turn glucose depletion, repression of oxidative stress, potentiation of the antioxidant defense system, and inhibition of pancreatic inflammation.

Inhibition of Ca 2+ entry into the hippocampus and dorsal root ganglion (DRG) through inhibition of N-methyl-D-aspartate (NMDA) receptor antagonist drugs is the current standard of care in neuronal diseases such as Alzheimer's disease, dementia, and peripheral pain. Oxidative stress activates Ca 2+ -permeable TRPM2 and TRPV1, and recent studies indicate that selenium (Se) is a potent TRPM2 and TRPV1 channel antagonist in the hippocampus and DRG. In this study, we investigated the neuroprotective properties of Se in primary hippocampal and DRG neuron cultures of aged rats when given alone or in combination with scopolamine (SCOP). Thirty-two aged (18-24 months old) rats were divided into four groups. The first and second groups received a placebo and SCOP (1 mg/kg/day), respectively. The third and fourth groups received intraperitoneal Se (1.5 mg/kg/ over day) and SCOP + Se, respectively. The hippocampal and DRG neurons also were stimulated in vitro with a TRPV1 channel agonist (capsaicin) and a TRPM2 channel agonist (cumene hydroperoxide). We found that Se was fully effective in reversing SCOP-induced TRPM2 and TRPV1 current densities as well as errors in working memory and reference memory. In addition, Se completely reduced SCOP-induced oxidative toxicity by modulating lipid peroxidation, reducing glutathione and glutathione peroxidase. The Se and SCOP + Se treatments also decreased poly (ADP-ribose) polymerase activity, intracellular free Ca 2+ concentrations, apoptosis, and caspase 3, caspase 9, and mitochondrial membrane depolarization values in the hippocampus. In conclusion, the current study reports on the cellular level for SCOP and Se on the different endocytotoxic cascades for the first time. Notably, the research indicates that Se can result in remarkable neuroprotective and memory impairment effects in the hippocampal neurons of rats. Graphical abstract Possible molecular pathways of involvement of selenium (Se) in scopolamine (SCOP) induced apoptosis, oxidative stress, and calcium accumulation through TRPM2 and TRPV1 channels in the hippocampus neurons of aged rats. The TRPM2 channel is activated by ADP-ribose and oxidative stress, although it is inhibited by ACA. The TRPV1 channel is activated by oxidative stress and capsaicin, and it is blocked by capsazepine (CPZ). The beta-amyloid plaque induces oxidative stress in hippocampus. SCOP can result in augmented ROS release in hippocampal neurons, leading to Ca 2+ uptake through TRPM2 and TRPV1 channels. Mitochondria were reported to accumulate Ca 2+ provided that intracellular Ca 2+ rises, thereby leading to the depolarization of mitochondrial membranes and release of apoptosis-inducing factors such as caspase 3 and caspase 9. Se reduced TRPM2 and TRPV1 channel activation through the modulation of aging oxidative reactions and Se-dependent glutathione peroxidase (GSH-Px) antioxidant pathways.

By a systematic review and meta-analysis to investigate clinically relevant effects of selenium supplementation in patients with chronic autoimmune thyroiditis. Controlled trials in adults (≥18 years) with autoimmune thyroiditis, comparing selenium with or without levothyroxine substitution, versus placebo and/or levothyroxine substitution, were eligible for inclusion. Identified outcomes were serum thyrotropin (thyroid stimulating hormone) levels in LT4-untreated patients, thyroid ultrasound and health-related quality of life. Eleven publications, covering nine controlled trials, were included in the systematic review. Random effects model meta-analyses were performed in weighted mean difference for thyroid stimulating hormone, ultrasound and health-related quality of life. Quality of evidence was assessed per outcome, using GRADE. Meta-analyses showed no change in thyroid stimulating hormone, or improvements in health-related quality of life or thyroid echogenicity (ultrasound), between levothyroxine substitution-untreated patients assigned to selenium supplementation or placebo. Three trials found some improvement in wellbeing in patients receiving levothyroxine substitution, but could not be synthesized in a meta-analysis. The quality of evidence ranged from very low to low for thyroid stimulating hormone as well as ultrasound outcomes, and low to moderate for health-related quality of life, and was generally downgraded due to small sample sizes. We found no effect of selenium supplementation on thyroid stimulating hormone, health-related quality of life or thyroid ultrasound, in levothyroxine substitution-untreated individuals, and sporadic evaluation of clinically relevant outcomes in levothyroxine substitution-treated patients. Future well-powered RCTs, evaluating e.g. disease progression or health-related quality of life, are warranted before determining the relevance of selenium supplementation in autoimmune thyroiditis., Competing Interests: The authors declare that they have no conflict of interests.

To our knowledge, data on the effects of selenium supplementation on glycemic control and lipid concentrations in patients with diabetic nephropathy (DN) are scarce. The current study was done to determine the effects of selenium supplementation on glycemic control and lipid concentrations in patients with DN. This was a randomized double-blind placebo-controlled clinical trial in which 60 patients with DN were randomly allocated into two groups to receive either 200 μg of selenium supplements (n = 30) or placebo (n = 30) daily for 12 weeks. Blood sampling was performed for the quantification of glycemic indicators and lipid profiles at the onset of the study and after 12 weeks of intervention. Selenium supplementation for 12 weeks resulted in a significant decrease in serum insulin levels (P = 0.01), homeostasis model of assessment-estimated insulin resistance (HOMA-IR) (P = 0.02), homeostasis model of assessment-estimated B cell function (HOMA-B) (P = 0.009) and a significant rise in plasma glutathione peroxidase (GPx) (P = 0.001) compared with the placebo. Taking selenium supplements had no significant effects on fasting plasma glucose (FPG), quantitative insulin sensitivity check index (QUICKI) and lipid profiles compared with the placebo. Overall, our study demonstrated that selenium supplementation for 12 weeks among patients with DN had beneficial effects on plasma GPx, serum insulin levels, HOMA-IR, and HOMA-B, while it did not affect FPG, QUICKI, and lipid profiles.

Various dietary agents can modulate tumor invasiveness. The current study explored whether selenoglycoproteins (SeGPs) extracted from selenium-enriched yeast affect tumor cell homing and growth in the brain. Mice were fed diets enriched with specific SeGPs (SeGP40 or SeGP65, 1 mg/kg Se each), glycoproteins (GP40 or GP65, 0.2-0.3 mg/kg Se each) or a control diet (0.2-0.3 mg/kg Se) for 12 weeks. Then, murine Lewis lung carcinoma cells were infused into the brain circulation. Analyses were performed at early (48 h) and late stages (3 weeks) post tumor cell infusion. Imaging of tumor progression in the brain revealed that mice fed SeGP65-enriched diet displayed diminished metastatic tumor growth, fewer extravasating tumor cells and smaller metastatic lesions. While administration of tumor cells resulted in a significant upregulation of adhesion molecules in the early stage of tumor progression, overexpression of VCAM-1 (vascular call adhesion molecule-1) and ALCAM (activated leukocyte cell adhesion molecule) messenger RNA (mRNA) was diminished in SeGP65 supplemented mice. Additionally, mice fed SeGP65 showed decreased expression of acetylated NF-κB p65, 48 h post tumor cell infusion. The results indicate that tumor progression in the brain can be modulated by specific SeGPs. Selenium-containing compounds were more effective than their glycoprotein controls, implicating selenium as a potential negative regulator of metastatic process.

The interactions between the essential element selenium (Se) and the toxic element lead (Pb) have been reported extensively; however, little is known about the effect of Se on Pb toxicity and the expression pattern of selenoproteins in the cartilage of chicken. To investigate the effects of Se on Pb toxicity and the messenger RNA (mRNA) expressions of selenoproteins in cartilage tissue, an in vitro study was performed on 1-day-old broiler chickens (randomly allocated into four groups) with diet of different concentration of Se and Pb. After 90 days, the meniscus cartilage and sword cartilage tissue were examined for the mRNA levels of 25 selenoprotein genes. The results showed that Se and Pb influenced the expression of selenoprotein genes in the chicken cartilage tissue. In detail, Se could alleviate the downtrend of the expression of Gpx1, Gpx2, Gpx4, Txnrd2, Txnrd3, Dio1, Dio2, Seli, Selu, Sepx1, Selk, Selw, Selo, Selm, Sep15, Sepnn1, Sels, and Selt induced by Pb exposure in the meniscus cartilage. In the sword cartilage, Se alleviated the downtrend of the expression of Gpx2, Gpx3, Gpx4, Txnrd1, Txnrd2, Dio2, Dio3, Seli, Selh, SPS2, Sepx1, Selk, Selw, Selo, Selm, Sep15, Selpb, Sepn1, and Selt induced by Pb exposure. The present study provided some compensated data about the roles of Se against Pb toxicity in the regulation of selenoprotein expression.

Oxidative stress is one of the major mechanisms implicated in inorganic arsenic poisoning. Punica granatum is known by its free radical scavenging properties. The aim of this study was to evaluate the protective role of combined selenium and P. granatum against arsenic-induced liver injury. Seventy-five female albino rats were divided into five groups (of 15 rats each). Toxicity was induced by oral sodium arsenite (5.5 mg/kg body weight (bw) daily) (group ІІ). Treatment of arsenic-intoxicated rats was induced by daily oral administration of sodium selenite (3 mg/kg bw) (group ІІІ), 100 mg of P. granatum ethanol extract per kilogram body weight dissolved in 300 mL distilled water in three divided doses (100 mL of this suspension every 8 h) (group IV), and combined daily oral treatment with both selenite and P. granatum ethanol extract (group V). After 3 weeks, serum and liver tissues were obtained from the decapitated rats for different estimations. Hepatotoxicity was demonstrated by significant elevation in liver weights and activities of liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and decrease in serum total proteins and albumin (p < 0.05) which were confirmed by histopathological examination. Additionally, arsenic hepatotoxicity led to an increased values of malondialdehyde, advanced oxidation protein products, nitric oxide, and interleukin-6 (IL-6) (p < 0.05) and decreased activity of thioredoxin reductase, values of total anti-oxidant capacity, and nuclear factor erythroid 2-related factor 2 (Nrf2) gene expression. Significant improvement in all assessed parameters was observed in rat group treated with both P. granatum and selenium. It was concluded that combined P. granatum and selenium treatment had a synergistic hepatoprotective effect against arsenic toxicity through activation of Nrf2 anti-oxidant pathway.

This study was conducted using 360 broiler chickens to evaluate the effects of dietary vitamin E (0, 125, and 250 mg/kg), selenium (0, 0.5, and 1 mg/kg), or their different combinations on performance, meat yield, and selenium content and lipid oxidation of breast meat of broilers raised under either a thermoneutral (TN, 24 °C constant) or heat stress (HS, 24 to 37 °C cycling) condition. There was a reduction (P < 0.05) in body weight and feed intake and an increase (P < 0.05) in feed conversion ratio when broilers exposed to HS. In the overall period of the study (1 to 49 days), growth performance of TN broilers was not affected (P < 0.05) by vitamin E and selenium supplementation. However, under HS condition, broilers receiving 250 mg/kg vitamin E and 0.5 mg/kg selenium consumed more (P < 0.05) feed than that of broilers receiving 250 mg/kg vitamin E alone, but similar (P > 0.05) to that of broilers receiving 250 mg/kg vitamin E and 1 mg/kg selenium. The malondialdehyde (MDA) content of the breast meat was increased (P < 0.05), but its selenium content was decreased (P < 0.05) by exposure to HS. The breast meat selenium content was increased (P < 0.05) by selenium supplementation. The breast meat selenium content was decreased (P < 0.05) by supplementation of 250 mg/kg vitamin E to diet of TN birds. However, the breast meat selenium content was increased (P < 0.05) by supplementation of vitamin E under HS condition. The breast meat MDA content was not affected (P > 0.05) by dietary treatments under TN condition. However, the breast meat MDA content was decreased (P < 0.05) by both vitamin E and selenium supplementation under HS condition, and the lowest MDA content was observed in the breast meat of broilers receiving combination of 125 mg/kg vitamin E and 1 mg/kg selenium. The results showed that supplementation of selenium and vitamin E was capable of increasing the selenium content of the breast meat and could improve the lipid oxidation of the breast meat when broilers reared under HS condition.

We herein examined the effects of different doses, forms, and compatibilities of selenium on a canine mammary gland tumor cell line, CTM1211, and explored the related mechanisms. Three selenium compounds, sodium selenite (SSE), methylseleninic acid (MSA), and methylselenocysteine (MSC), were selected for these experiments, and cyclophosphamide (CTX) served as a positive control. In the cell viability assay, the cell viability of each group at 48/72 h decreased significantly compared with the control group (p < 0.05), and the cell viability of the CTX + MSA group was lower than that of CTX and MSA groups (p < 0.05). Moreover, the inhibitory effect of selenium on cell proliferation was time-dependent but not concentration-dependent. In the cell apoptosis assay, the apoptosis values of each group increased significantly compared with the control group, and the apoptosis values of the CTX + MSA group increased the most significantly (p < 0.01). The protein and mRNA expression levels of vascular endothelial growth factor-alpha (VEGF-alpha), angiopoietin-2 (Ang-2), and hypoxia inducible factor-1 alpha (HIF-1 alpha) were downregulated in each group, while that of phosphatase and tensin homolog (PTEN) were upregulated (p < 0.05). In conclusion, these three selenium compounds, especially MSA, could significantly inhibit the viability and growth of the CTM1211 cell line, which is partly due to the induction of apoptosis and regulation of tumor angiogenesis.

In present study, selenium was selected for evaluating effect of selenium on aluminum chloride (AlCl3)-induced Alzheimer's disease in rats. Thirty Wistar rats were divided into five groups of six in each. Group I (control) received distilled water, group II-AlCl3 (100 mg/kg, p.o.), group III-selenium (1 mg/kg, p.o.), group IV-AlCl3 + vitamin E (100 mg/kg, p.o. + 100 mg/kg, p.o.), and group V-AlCl3 + selenium (100 mg/kg, p.o. + 1 mg/kg, p.o.) for 21 days. At end of experiment, various behavioral, biochemical, and histopathological assessments were carried out. The animals showed increase in time to reach platform in Morris water maze and decreased step-down latencies in passive avoidance test indicating learning and memory impairment in aluminum chloride-treated group, but administration of selenium decreased time to reach platform in Morris water maze, increased step-down latencies, and strengthened its memory action in drug-treated animals. There was decrease in muscle strength measured by rotarod test indicating motor incoordination and decrease in locomotor activity assessed by actophotometer test in AlCl3 control group, whereas in selenium-AlCl3 group, there was improvement in muscle strength and locomotion. Biochemical analysis of the brain revealed that chronic administration of AlCl3 significantly increased lipid peroxidation and decreased levels of acetyl cholinesterase, catalase, reduced glutathione and glutathione reductase, an index of oxidative stress process. Administration of selenium attenuated lipid peroxidation and ameliorated the biochemical changes. There were marked changes at subcellular level observed by histopathology studies in AlCl3 group, and better improvement in these changes was observed in selenium + AlCl3group. Therefore, this study strengthens the hypothesis that selenium helps to combat oxidative stress produced by accumulation of AlCl3 in the brain and helps in prophylaxis of Alzheimer's diseases.

Migraine headaches are considered to be associated with increased mitochondrial energy metabolism. Mitochondrial oxidative stress is also important in migraine headache pathophysiology although riboflavin and selenium (Se) induced a modulator role on mitochondrial oxidative stress in the brain. The current study aimed to determine the effects of Se with/without riboflavin on the microsomal membrane Ca(2+)-ATPase (MMCA), lipid peroxidation, antioxidant, and electroencephalography (EEG) values in glyceryl trinitrate (GTN)-induced brain injury rats. Thirty-two rats were randomly divided into four groups. The first group was used as the control, and the second group was the GTN group. Se and Se plus oral riboflavin were administered to rats constituting the third and fourth groups for 10 days prior to GTN administration. The second, third, and fourth groups received GTN to induce headache. Ten hours after the administration of GTN, the EEG records and brain cortex samples were obtained for all groups. Brain cortex microsomes were obtained from the brain samples. The brain and microsomal lipid peroxidation levels were higher in the GTN group compared to the control group, whereas they were decreased by selenium and selenium + riboflavin treatments. Vitamin A, vitamin C, vitamin E, and reduced glutathione (GSH) concentrations of the brain and MMCA, GSH and glutathione peroxidase values of microsomes were decreased by the GTN administration, although the values and β-carotene concentrations were increased by Se and Se + riboflavin treatments. There was no significant change in EEG records of the four groups. In conclusion, Se with/without riboflavin administration protected against GTN-induced brain oxidative toxicity by inhibiting free radicals and the modulation of MMCA activity and supporting the antioxidant redox system.

The trace element selenium and selenocysteine-carrying selenoproteins play a pivotal role in the brain. Beside the essential function during development and maintenance of brain action, selenium has also been associated with several neurological and neuro-oncological conditions. Reliable supply of selenium is important since selenium compounds can affect tumor microenvironment and neoangiogenesis in malignant gliomas (WHO grade III and IV [glioblastoma, GBM]) via induction of apoptosis and alteration of matrix metalloproteinases expression. Here, we summarize recent findings focusing on the anti-toxicity and cancer-preventive properties of selenium and their implication in current multimodal therapies including temozolomide (Temodal), cyclophosphamide (Endoxan), and cisplatin (DDP, Platiblastin, and Platinol). We shed light on unintended side effects in chemotherapy and the developments of novel combinatorial chemotherapeutics with selenium compounds. We found that selenium and selenium compounds have dual action profiles with direct anti-cancer and chemotherapy-intensifier effects as well as neuroprotective and cytoprotective agents. Current selenium trials and selenium supplementation with focus on neuro-oncology will be discussed with regard to low-adequate-to-high/toxic selenium status.

Cumulative evidence indicates that oxidative stress and inflammation frequently occurs in patients undergoing maintenance hemodialysis (HD) and as a result of overproduction of reactive oxygen species (ROS) and a decrease of antioxidant defenses such as selenium (Se). Previous studies in our laboratory showed that the supplementation of 1 unit of Brazil nut (the richest known food source of Se) a day during 3 months is effective to improve Se status and increase glutathione peroxidase (GPx) levels in HD patients. The aim of this study was to evaluate the effect of Brazil nut supplementation on oxidative stress and inflammation markers in HD patients. Forty HD patients from Rio de Janeiro, Brazil were studied. All patients received one nut per day for 3 months. The Se plasma levels and GPx, 8-isoprostane, 8-hydroxy-2-deoxyguanosine (8-OHdG), and cytokine (TNF-α and IL-6) levels and lipid profile were determined before and after 3 months of supplementation. The plasma Se and GPx activity increased, while cytokines, 8-OHdG, and 8-isoprostane plasma levels decreased significantly after 3 months supplementation. HDL-c levels increased and LDL-c levels decreased significantly. These data suggest that the consumption of only one Brazil nut per day during 3 months was effective to reduce the inflammation, oxidative stress markers, and the atherogenic risk, thereby increasing the antioxidant defenses in HD patients. Our results indicate that Brazil nut as Se source plays an important role as an anti-inflammatory and antioxidant agent in HD patients.

Scleroderma, sclerosis of the skin, is a severe autoimmune disease refractant to all kind of treatments. To study the in vivo effects of a combination of three oligoelements selenium (Se), zinc (Zn), and manganese (Mn) plus Lachesis muta venom (O-LM) on the bleomycin (BLM)-induced scleroderma mouse experimental model. C3H mice were randomly divided into four groups: control (phosphate-buffered saline (PBS)), O-LM, BLM, and BLM + O-LM. All administrations were performed subcutaneously into the back of mice. BLM was injected 5 days per week for three consecutive weeks and O-LM was administered simultaneously with BLM from the beginning of the experiments and lasted for 3 weeks after the final BLM or PBS injection (for O-LM and BLM + O-LM groups), when animals were sacrificed and histopathological, immunohistochemical, thiobarbituric acid reactive species (TBARS) evaluation, and autoantibodies detection were determined. O-LM significantly reduced BLM-induced enhanced dermal thickness (605 ± 47 vs. 956 ± 59 μm, P < 0.01), collagen deposition, and mast cells infiltration (43.1 ± 1.0 vs. 102 ± 14.1 mast cells, P < 0.05). O-LM administration significantly blocked BLM-induced oxidative damage and the enhanced immunoreactive fibroblasts for α-smooth muscle actin while reduced BLM-induced autoantibodies that strongly react mainly with skin and spleen. O-LM significantly reduced BLM-induced scleroderma through the modulation of antioxidant and immunological pathways.

It is well known that oxidative stress plays an important role in the etiology of epilepsy. We investigated effects of selenium (Se) and topiramate (TPM) combination supplementation on antioxidant and oxidant values in control and patients with epilepsy and refractory epilepsy. For the aim, we used control (n = 19), epilepsy + TPM (n = 19), epilepsy + TPM + Se (n = 15) groups. We also used control (n = 15), refractory epilepsy (n = 15), and refractory epilepsy + Se (n = 8) groups. TPM (0.2 mg/daily) and Se, as sodium selenite (twice daily with 0.1 mg doses), were orally supplemented to the patients for 45 days. Erythrocyte lipid peroxidation levels were higher in refractory epilepsy groups than in control although its level and seizure numbers were decreased in TPM and TPM + Se supplemented groups of the patients. The erythrocyte reduced glutathione (GSH), glutathione peroxidase (GSH-Px), plasma total antioxidant status (TAS), and vitamin E concentration in refractory epilepsy group were lower than in control. However, the erythrocyte and plasma TAS, erythrocyte GSH and GSH-Px, and plasma vitamins A and C values were increased either by Se or Se + TPM in epilepsy and refractory epilepsy groups. There were no effects of TPM and Se on plasma β-carotene values in the groups. In conclusion, TPM and selenium caused protective effects on the epilepsy and refractory epilepsy-induced oxidative injury by inhibiting free radical production and supporting antioxidant redox system.

Diabetes mellitus is associated to a reduction of antioxidant defenses that leads to oxidative stress and complications in diabetic individuals. The present study was undertaken to investigate the effect of selenium on blood biochemical parameters, antioxidant enzyme activities, and tissue zinc levels in alloxan-induced diabetic rats fed a zinc-deficient diet. The rats were divided into two groups; the first group was fed a zinc-sufficient diet, while the second group was fed a zinc-deficient diet. Half of each group was treated orally with 0.5 mg/kg sodium selenite. Tissue and blood samples were taken from all animals after 28 days of treatment. At the end of the experiment, the body weight gain and food intake of the zinc-deficient diabetic animals were lower than that of zinc-adequate diabetic animals. Inadequate dietary zinc intake increased glucose, lipids, triglycerides, urea, and liver lipid peroxidation levels. In contrast, serum protein, reduced glutathione, plasma zinc and tissue levels were decreased. A zinc-deficient diet led also to an increase in serum glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, and liver glutathione-S-transferase and to a decrease in serum alkaline phosphatase activity and glutathione peroxidase. Selenium treatment ameliorated all the values approximately to their normal levels. In conclusion, selenium supplementation presumably acting as an antioxidant led to an improvement of insulin activity, significantly reducing the severity of zinc deficiency in diabetes.

The objective of this study was to evaluate the effects of supplemental selenium (Se) on expression of endothelin-1 (ET-1) and its receptors in cultured chick embryos pulmonary microvascular endothelial cells (PMVECs). To accomplish this, PMVECs were treated in Se-deficient or Se-supplement (12, 24, 50, 100 ng/ml) culture medium for 48 h. Low Se medium was achieved by reducing serum concentrations and the essential growth factors were added. After the incubation, the effects of supplemental Se on ET-1 and its receptors gene expression were assessed by quantitative real-time PCR (qRT-PCR). Compared with the control group, our results showed that among the different concentrations of Se supplement, the levels of ET-1 gene expression treated with both the moderate Se doses (24, 50 ng/ml, P < 0.01, P < 0.01, respectively) and the high doses (100 ng/ml, P < 0.05) were noticeably decreased, the low-dose group (12 ng/ml), which showed no changes. Meanwhile, Se supplement (24, 50, 100 ng/ml) was found to be effective in reducing the expression levels of ETA (P < 0.01, P < 0.05, P < 0.05, respectively) in cultured PMVECs grown in low Se medium. However, there were no significant changes (P > 0.05) in ETB mRNA levels during the cell proliferation. These observations indicated that Se may play both direct and indirect role in the regulation of ET-1 and its receptors gene expression and their production in avian PMVECs. Se supplement decreases in ET-1 and ETA production in Se-deficient PMVECs may partly explain the mechanism of the protective effects of the Se on the cardiovascular system.

Psoriasis is a chronic, immune-mediated skin disease characterized by production of reactive oxygen species due to the activation of tumor necrosis factor alpha (TNF-α), which is thought to be an important factor in inducing and maintaining psoriatic lesions. As an external factor, ultraviolet B (UVB) radiation stimulates TNF-α production and secretion by human keratinocytes in vitro and can also reach the upper dermis and suppress endothelial cells in vitro. The selenium level in psoriatic patients has been found to be lower than expected, but studies on its role in the pathogenesis of the disease are scarce. Selenium can influence immune response by changing the expression of cytokines and their receptors or by making immune cells more resistant to oxidative stress. It was reported that selenium supplementation had inhibitory effects on TNF-α levels in patients with psoriasis, but the details are not completely elucidated. Selenium compounds are also known to prevent the in vitro release of UVB-induced proinflammatory cytokines by inhibition of mRNA in human keratinocytes. In the present review, the protective role of selenium in oxidative stress, lesions, and immune system regulation in patients with psoriasis is summarized.