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International Journal of Molecular... Oct 2021Functions of selenium are diverse as antioxidant, anti-inflammation, increased immunity, reduced cancer incidence, blocking tumor invasion and metastasis, and further... (Review)
Review
Functions of selenium are diverse as antioxidant, anti-inflammation, increased immunity, reduced cancer incidence, blocking tumor invasion and metastasis, and further clinical application as treatment with radiation and chemotherapy. These functions of selenium are mostly related to oxidation and reduction mechanisms of selenium metabolites. Hydrogen selenide from selenite, and methylselenol (MSeH) from Se-methylselenocyteine (MSeC) and methylseleninicacid (MSeA) are the most reactive metabolites produced reactive oxygen species (ROS); furthermore, these metabolites may involve in oxidizing sulfhydryl groups, including glutathione. Selenite also reacted with glutathione and produces hydrogen selenide via selenodiglutathione (SeDG), which induces cytotoxicity as cell apoptosis, ROS production, DNA damage, and adenosine-methionine methylation in the cellular nucleus. However, a more pronounced effect was shown in the subsequent treatment of sodium selenite with chemotherapy and radiation therapy. High doses of sodium selenite were effective to increase radiation therapy and chemotherapy, and further to reduce radiation side effects and drug resistance. In our study, advanced cancer patients can tolerate until 5000 μg of sodium selenite in combination with radiation and chemotherapy since the half-life of sodium selenite may be relatively short, and, further, selenium may accumulates more in cancer cells than that of normal cells, which may be toxic to the cancer cells. Further clinical studies of high amount sodium selenite are required to treat advanced cancer patients.
Topics: Antineoplastic Agents; Glutathione; Humans; Methanol; Neoplasms; Organoselenium Compounds; Selenium Compounds; Sodium Selenite
PubMed: 34769276
DOI: 10.3390/ijms222111844 -
Journal of Trace Elements in Medicine... Sep 2016A significant percentage of cancer patients develop secondary lymphedema after surgery or radiotherapy. The preferred treatment of secondary lymphedema is complex... (Review)
Review
A significant percentage of cancer patients develop secondary lymphedema after surgery or radiotherapy. The preferred treatment of secondary lymphedema is complex physical therapy. Pharmacotherapy, for example with diuretics, has received little attention, because they were not effective and only offered short-term solutions. Sodium selenite showed promise as a cost-effective, nontoxic anti-inflammatory agent. Treatment with sodium selenite lowers reactive oxygen species (ROS) production, causes a spontaneous reduction in lymphedema volume, increases the efficacy of physical therapy for lymphedema, and reduces the incidence of erysipelas infections in patients with chronic lymphedema. Besides biological effects in reducing excessive production of ROS, sodium selenite also displays various pharmacological effects. So far the exact mechanisms of these pharmacological effects are mostly unknown, but probably include inhibition of adhesion protein expression.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Humans; Lymphedema; Physical Therapy Modalities; Platelet Glycoprotein GPIb-IX Complex; Reactive Oxygen Species; Sodium Selenite
PubMed: 27267968
DOI: 10.1016/j.jtemb.2016.05.005 -
Science Advances Jan 2019Currently available cell culture media may not reproduce the in vivo metabolic environment of tumors. To demonstrate this, we compared the effects of a new physiological...
Currently available cell culture media may not reproduce the in vivo metabolic environment of tumors. To demonstrate this, we compared the effects of a new physiological medium, Plasmax, with commercial media. We prove that the disproportionate nutrient composition of commercial media imposes metabolic artifacts on cancer cells. Their supraphysiological concentrations of pyruvate stabilize hypoxia-inducible factor 1α in normoxia, thereby inducing a pseudohypoxic transcriptional program. In addition, their arginine concentrations reverse the urea cycle reaction catalyzed by argininosuccinate lyase, an effect not observed in vivo, and prevented by Plasmax in vitro. The capacity of cancer cells to form colonies in commercial media was impaired by lipid peroxidation and ferroptosis and was rescued by selenium present in Plasmax. Last, an untargeted metabolic comparison revealed that breast cancer spheroids grown in Plasmax approximate the metabolic profile of mammary tumors better. In conclusion, a physiological medium improves the metabolic fidelity and biological relevance of in vitro cancer models.
Topics: Arginine; Argininosuccinate Lyase; Cell Line, Tumor; Cell Proliferation; Culture Media; Female; Ferroptosis; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Lipid Peroxidation; Models, Biological; Pyruvic Acid; Sodium Selenite; Spheroids, Cellular; Triple Negative Breast Neoplasms; Tumor Microenvironment; Urea
PubMed: 30613774
DOI: 10.1126/sciadv.aau7314 -
Frontiers in Pharmacology 2021Vascular remodeling (VR), induced by the massive proliferation and reduced apoptosis of vascular smooth muscle cells (VSMCs), is primarily responsible for many...
Vascular remodeling (VR), induced by the massive proliferation and reduced apoptosis of vascular smooth muscle cells (VSMCs), is primarily responsible for many cardiovascular conditions, such as restenosis and pulmonary arterial hypertension. Sodium selenite (SSE) is an inorganic selenium, which can block proliferation and stimulate apoptosis of tumor cells; still, its protective effects on VR remains unknown. In this study, we established rat models with carotid artery balloon injury and monocrotaline induced pulmonary arterial hypertension and administered them SSE (0.25, 0.5, or 1 mg/kg/day) orally by feeding tube for 14 consecutive days. We found that SSE treatment greatly ameliorated the development of VR as evidenced by an improvement of its characteristic features, including elevation of the ratio of carotid artery intimal area to medial area, right ventricular hypertrophy, pulmonary arterial wall hypertrophy and right ventricular systolic pressure. Furthermore, PCNA and TUNEL staining of the arteries showed that SSE suppressed proliferation and enhanced apoptosis of VSMCs in both models. Compared with the untreated VR rats, lower expression of PCNA and CyclinD1, but higher levels of Cleaved Caspase-3 and Bax/Bcl-2 were observed in the SSE-treated rats. Moreover, the increased protein expression of MMP2, MMP9, p-AKT, p-ERK, p-GSK3β and β-catenin that occurred in the VR rats were significantly inhibited by SSE. Collectively, treatment with SSE remarkably attenuates the pathogenesis of VR, and this protection may be associated with the inhibition of AKT and ERK signaling and prevention of VSMC's dysfunction. Our study suggest that SSE is a potential agent for treatment of VR-related diseases.
PubMed: 33790787
DOI: 10.3389/fphar.2021.618493 -
Biophysics 2022The review considers the role that selenium plays in RNA virus infections and, in particular, COVID-19. Many RNA viruses are selenium dependent because antisense...
The review considers the role that selenium plays in RNA virus infections and, in particular, COVID-19. Many RNA viruses are selenium dependent because antisense interactions arise between viral RNAs and host mRNA regions containing the selencysteine insertion sequence to cause selenium deficiency, oxidative stress, immune response impairment, etc. Sodium selenite is a licensed selenium-containing product and is widely used in medicine, veterinary, and agriculture. Its advantages include the following. Sodium selenite rapidly penetrates through cell membranes in all tissues of the body; is intensely involved in metabolic processes accompanied by oxidation of sulfur-containing cell proteins; exerts an antiaggregation effect by reducing thromboxane activity; interrupts the contact of a virion (SARS-CoV-1 and SARS-CoV-2) with the membrane of a healthy cell; and suppresses NF-κB activity, which significantly increases in coronavirus infections. Arguments supporting the use of sodium selenite as adjuvant therapy in COVID-19 are discussed.
PubMed: 36567968
DOI: 10.1134/S0006350922050074 -
Cellular Physiology and Biochemistry :... Mar 2022Colitis is a main presentation of inflammatory bowel disease (IBD) and yet, has no definitive cure. Currently, corticosteroids, anti-tumor necrosis factor (anti-TNF)...
BACKGROUND/AIMS
Colitis is a main presentation of inflammatory bowel disease (IBD) and yet, has no definitive cure. Currently, corticosteroids, anti-tumor necrosis factor (anti-TNF) agents and 5-aminosalicylic acid derivatives are prescribed for management of colitis. Except their failure rate, they are not always tolerated because of their severe adverse effects. Additive formulas with fewer adverse effects may improve the treatment of colitis.
METHODS
In this study, colitis was induced with intra-rectal injection of three concentrations of acetic acid (4, 6 and 8 v/v). Each group received sodium selenite (0.5 mg/kg) or saline, gavaged on days 0 and 1 for treatment. Two days after induction of colitis, rats were sacrificed and the end part of their colons were resected for macroscopic and microscopic evaluation and molecular measurement.
RESULTS
Sodium selenite improved macroscopic and microscopic view of the colon, decreased cryptitis, crypt abscess and inflammatory cells infiltration and partly maintained mucosal structure. Sodium selenite markedly reduced tissue levels of malondialdehyde (MDA), TNF-α and interferon γ (INF-γ) and decreased myeloperoxidase (MPO) activity. Treatment with sodium selenite also significantly downregulated IL17, IL22, indoleamine 2,3-dioxygenase (IDO1), and kynurenine levels. Western blotting revealed that sodium selenite prevented apoptosis by increasing bcl2/Bax ratio. Furthermore, our findings showed that sodium selenite significantly downregulated the upstream inflammatory molecules such as nuclear factor kappa B (NF-κB) and toll-like receptor 4 (TLR4) in colitis.
CONCLUSION
These findings show that sodium selenite alleviates inflammatory response and oxidative stress and protects against colitis.
Topics: Acetic Acid; Animals; Colitis; Colon; Kynurenine; NF-kappa B; Rats; Signal Transduction; Sodium Selenite; Toll-Like Receptor 4; Tumor Necrosis Factor Inhibitors
PubMed: 35263537
DOI: 10.33594/000000504 -
Neural Regeneration Research Dec 2022Ferroptosis is a recently discovered form of iron-dependent cell death, which occurs during the pathological process of various central nervous system diseases or...
Ferroptosis is a recently discovered form of iron-dependent cell death, which occurs during the pathological process of various central nervous system diseases or injuries, including secondary spinal cord injury. Selenium has been shown to promote neurological function recovery after cerebral hemorrhage by inhibiting ferroptosis. However, whether selenium can promote neurological function recovery after spinal cord injury as well as the underlying mechanism remain poorly understood. In this study, we injected sodium selenite (3 µL, 2.5 µM) into the injury site of a rat model of T10 vertebral contusion injury 10 minutes after spinal cord injury modeling. We found that sodium selenite treatment greatly decreased iron concentration and levels of the lipid peroxidation products malondialdehyde and 4-hydroxynonenal. Furthermore, sodium selenite increased the protein and mRNA expression of specificity protein 1 and glutathione peroxidase 4, promoted the survival of neurons and oligodendrocytes, inhibited the proliferation of astrocytes, and promoted the recovery of locomotive function of rats with spinal cord injury. These findings suggest that sodium selenite can improve the locomotive function of rats with spinal cord injury possibly through the inhibition of ferroptosis via the specificity protein 1/glutathione peroxidase 4 pathway.
PubMed: 35662217
DOI: 10.4103/1673-5374.339491 -
BMC Cancer Aug 2022Sodium selenite (SSE) has been reported to exert anti-tumor effects in several cancer cells. However, the underlying mechanisms in renal cancer are yet to be elucidated....
BACKGROUND
Sodium selenite (SSE) has been reported to exert anti-tumor effects in several cancer cells. However, the underlying mechanisms in renal cancer are yet to be elucidated. The effects of SSE on the proliferation, metastasis, and apoptosis of renal cancer cells, as well as its mechanism, were investigated in this study.
METHODS
ACHN and 786-O renal cancer cells were treated with different concentrations of SSE, MTT, and colony formation assays were used to detect the proliferation ability of cells. The migration of cells was detected using scratch-wound-healing and transwell-migration assays. The effect of SSE on apoptosis was assessed by AnnexinV-FITC/PI double staining. Besides, Western blotting was employed to detect the protein-expression level and elucidate the underlying pathways. We also made subcutaneous xenografts in athymic mice to verify the effect of SSE on tumor growth in vivo.
RESULTS
Our results demonstrated that treatment with SSE resulted in significant inhibition of cell proliferation and migration. Flow cytometry and Western blot confirmed that SSE induced apoptosis via the endogenous apoptotic pathway. We also confirmed that SSE treatment causes an increase in intracellular reactive oxygen species (ROS) levels, resulting in the inhibition of nuclear transcription factor-κB (NF-κB) signaling. Modulation of the ROS level by the chemical inhibitor N-acetyl-cysteine reversed the effect of SSE on cells. Similarly, subcutaneous xenografts in athymic mice models showed that SSE inhibits tumor growth in vivo.
CONCLUSION
These results indicate that SSE inhibits proliferation and migration and induces apoptosis via ROS mediated inhibition of NF-κB signaling in renal cancer cells.
Topics: Animals; Apoptosis; Carcinoma, Renal Cell; Cell Line, Tumor; Cell Proliferation; Humans; Kidney Neoplasms; Mice; NF-kappa B; Reactive Oxygen Species; Sodium Selenite
PubMed: 35945549
DOI: 10.1186/s12885-022-09965-8 -
Cell Journal Jun 2022Osteoporosis is regarded as a silent disorder affecting bone slowly, leading to an increased risk of fractures. Lately, selenium has been found to be associated with the...
OBJECTIVE
Osteoporosis is regarded as a silent disorder affecting bone slowly, leading to an increased risk of fractures. Lately, selenium has been found to be associated with the acquisition and maintenance of bone health by affecting the bone remodeling process. However, the mechanism of action of selenium on bone is poorly understood. Here, the objective of this study is to examine the protective effects and mechanism of sodium selenite on the differentiation process of osteoblasts as well as under oxidative stress-induced conditions by evaluating the expression of osteoblast differentiation markers in the sodium selenite and/or hydrogen peroxide (HO)-treated MC3T3-E1 cell line.
MATERIALS AND METHODS
In this experimental study, we confirmed the inducible osteogenic effect of sodium selenite on MC3T3-E1 cells. Moreover, we investigated the recovery of expression levels of osteogenic markers of sodium selenite in (HO)-treated MC3T3-E1 cells.
RESULTS
It was observed that sodium selenite could promote alkaline phosphatase (ALP) activity and collagen synthesis in pre-osteoblasts. Also, sodium selenite enhanced the mRNA expression levels of osteogenic transcriptional factors, like osterix (OSX) and runt-related transcription factor 2 (Runx2). In addition, the terminal differentiation markers, such as osteocalcin (OCN) and collagen 1α (Col1α) were also increased after the treatment of sodium selenite. Also treatment of sodium selenite recused the (HO)-induced inhibition of osteoblastic differentiation of pre-osteoblasts cells via the WNT signaling pathway, implicating its antioxidant activity. Furthermore, sodium selenite restored the (HO) repressed β-catenin stability and axin-2 reporter activity in MC3T3-E1 cells.
CONCLUSION
It may be concluded that sodium selenite can stimulate bone formation and rescue the oxidative repression of osteogenesis by activating WNT signaling pathways. Further detailed studies on the role of selenium and its ability to stimulate bone formation via the WNT signaling pathway may project it as a potential therapeutic intervention for osteoporosis.
PubMed: 35892229
DOI: 10.22074/cellj.2022.8314 -
International Journal of Molecular... Mar 2021Metabolically active gasotransmitters (nitric oxide, carbon monoxide and hydrogen sulfide) are important signalling molecules that show therapeutic utility in oxidative... (Review)
Review
Metabolically active gasotransmitters (nitric oxide, carbon monoxide and hydrogen sulfide) are important signalling molecules that show therapeutic utility in oxidative pathologies. The reduced form of selenium, hydrogen selenide (HSe/HSe), shares some characteristics with these molecules. The simple selenide salt, sodium hydroselenide (NaHSe) showed significant metabolic activity, dose-dependently decreasing ex vivo O consumption (rat soleus muscle, liver) and transiently inhibiting mitochondrial cytochrome C oxidase (liver, heart). Pharmacological manipulation of selenoprotein expression in HepG2 human hepatocytes revealed that the oxidation status of selenium impacts on protein expression; reduced selenide (NaHSe) increased, whereas (oxidized) sodium selenite decreased the abundance of two ubiquitous selenoproteins. An inhibitor of endogenous sulfide production (DL-propargylglycine; PAG) also reduced selenoprotein expression; this was reversed by exogenous NaHSe, but not sodium hydrosulfide (NaHS). NaHSe also conferred cytoprotection against an oxidative challenge (HO), and this was associated with an increase in mitochondrial membrane potential. Anesthetized Wistar rats receiving intravenous NaHSe exhibited significant bradycardia, metabolic acidosis and hyperlactataemia. In summary, NaHSe modulates metabolism by inhibition of cytochrome C oxidase. Modification of selenoprotein expression revealed the importance of oxidation status of selenium therapies, with implications for current clinical practice. The utility of NaHSe as a research tool and putative therapeutic is discussed.
Topics: Animals; Antioxidants; Chemistry Techniques, Synthetic; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Gene Expression Regulation; Humans; Oxidation-Reduction; Oxidative Stress; Selenium Compounds; Selenoproteins; Sodium; Sodium Selenite
PubMed: 33806825
DOI: 10.3390/ijms22063258