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Selenium is an important dietary supplement and an essential trace element incorporated into selenoproteins with growth-modulating properties and cytotoxic mechanisms of action. However, different compounds of selenium usually possess a narrow nutritional or therapeutic window with a low degree of absorption and delicate safety margins, depending on the dose and the chemical form in which they are provided to the organism. Hence, selenium nanoparticles (SeNPs) are emerging as a novel therapeutic and diagnostic platform with decreased toxicity and the capacity to enhance the biological properties of Se-based compounds. Consistent with the exciting possibilities offered by nanotechnology in the diagnosis, treatment, and prevention of diseases, SeNPs are useful tools in current biomedical research with exceptional benefits as potential therapeutics, with enhanced bioavailability, improved targeting, and effectiveness against oxidative stress and inflammation-mediated disorders. In view of the need for developing eco-friendly, inexpensive, simple, and high-throughput biomedical agents that can also ally with theranostic purposes and exhibit negligible side effects, biogenic SeNPs are receiving special attention. The present manuscript aims to be a reference in its kind by providing the readership with a thorough and comprehensive review that emphasizes the current, yet expanding, possibilities offered by biogenic SeNPs in the biomedical field and the promise they hold among selenium-derived products to, eventually, elicit future developments. First, the present review recalls the physiological importance of selenium as an oligo-element and introduces the unique biological, physicochemical, optoelectronic, and catalytic properties of Se nanomaterials. Then, it addresses the significance of nanosizing on pharmacological activity (pharmacokinetics and pharmacodynamics) and cellular interactions of SeNPs. Importantly, it discusses in detail the role of biosynthesized SeNPs as innovative theranostic agents for personalized nanomedicine-based therapies. Finally, this review explores the role of biogenic SeNPs in the ongoing context of the SARS-CoV-2 pandemic and presents key prospects in translational nanomedicine.
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Overexposure to Se is detrimental to glucose metabolism, mainly because of its pro-oxidant effects and the overexpression of selenoproteins. This systematic review evaluated the effects of Se supplementation on glycaemic control in healthy rodents. The methodology followed the PRISMA. We searched the databases for articles published up to May 2022. The risk of bias and the methodological quality were assessed using the SYRCLE and CAMARADES. The results are presented as meta-analytic estimates of the overall standardised mean difference (SMD) and 95 % CI. Of the 2359 records retrieved, thirteen studies were included, of which eleven used sodium selenite and two used zero-valent Se nanoparticles as supplement. Nine studies were included in the meta-analysis. Generally, the risk of bias was high, and 23·1 % of the studies were of high quality. Supplementation with sodium selenite significantly increased fasting blood glucose (SMD = 2·57 (95 % CI (1·07, 4·07)), I2 = 93·5 % (P = 0·001). Subgroup analyses showed effect size was larger for interventions lasting between 21 and 28 d (SMD = 25·74 (95 % CI (2·29, 9·18)), I2 = 96·1 % (P = 0·001)) and for a dose of 864·7 µg/kg/d of sodium selenite (SMD = 10·26 (95 % CI (2·42, 18·11), I2 = 97·1 % (P = 0·010)). However, it did not affect glutathione peroxidase activity (SMD = 0·60 (95 % CI (-0·71, 1·91)), I2 = 83·2 % (P = 0·37)). The current analysis demonstrated the adverse effects of sodium selenite supplementation on glycaemic control in healthy rodents.
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Selênio , Selênio/farmacologia , Selenito de Sódio/farmacologia , Controle Glicêmico , Suplementos Nutricionais , Antioxidantes/farmacologiaRESUMO
Introdução: O Selênio ao mesmo tempo em que é tóxico se ingerido em grandes quantidades, é, também, micronutriente essencial em diversos processos metabólicos de animais e humanos. A deficiência de selênio vem sendo relacionada à predisposição em desenvolver doenças como o câncer, a diabetes, doenças cardiovasculares, entre outras. Na química medicinal, o selênio vem ganhando importância a partir da descoberta do ebselen, do ethaselen e do disseleneto de difenila. Objetivo: Essa revisão tem como objetivo compilar as principais informações disponíveis na literatura sobre a importância do selênio para a vida humana, proporcionando ao leitor uma visão geral do papel biológico desse elemento, das principais doenças relacionadas à deficiência de selênio, e da química medicinal dos três principais compostos de organoselênio. Metodologia: Foram recuperados artigos e teses acadêmicas que contemplassem o papel do selênio na bioquímica e na química medicinal, publicados em português e inglês, utilizando-se as bases de dados SciFinder, PubMed e Google Acadêmico. Resultados: Até o momento, foram identificadas 25 selenoproteínas que desempenham funções biológicas essenciais em animais e humanos. Sabe-se que a deficiência de selênio está diretamente relacionada à predisposição no desenvolvimento de diversas doenças. No campo da química medicinal, foi provado que é possível desenvolver moléculas bioativas, com baixa toxidez, contendo átomos de selênio em sua estrutura. Conclusão: O selênio é um elemento essencial à vida, sendo o componente-chave das selenoproteínas. O entendimento dos processos bioquímicos modulados por elas é imperativo para que os químicos medicinais possam desenvolver fármacos potentes contendo átomos de selênio em sua estrutura.
SUMMARY Introduction: Selenium is, at the same time, toxic if ingested in great amounts and an essential micronutrient to several metabolic processes in both animals and humans. Selenium deficiency is being related to an increased chance to develop diseases such as cancer, diabetes, cardiovascular diseases, among others. In medicinal chemistry, selenium has gained in importance since the discovery of ebselen, ethaselen, and diphenyl disselenide. Objectives: This review aims to compile the main data avail-able on the literature on the importance of selenium to human life, providing an overview of its biological role, the main diseases related to its deficiency, as well as the medicinal chemistry of the three most prominent organoselenium compounds. Methodology: Articles and academic thesis, published in English and Portuguese, showing the role of selenium in biochemistry and medicinal chemistry were recov-ered from SciFinder, PubMed, and Google Scholar. Results: So far, 25 selenopro-teins that play a biological role in humans and animals were identified. It is known that selenium deficiency is directly related not only to a predisposition to developing some diseases but is also the main cause of illnesses such as Keshan and Kashin-Beck. In the medicinal chemistry field, the development of selenium-containing bioactive compounds with low toxicity was proved possible. Conclusion: Selenium is an essential element to life, being the core component of selenoproteins. The under-standing of the biochemical processes modulated by those proteins is mandatory to medicinal chemists willing to develop potent organoselenium drugs.
Introducción: El selenioa la par que tóxico si se ingiere en grandes cantidades, es también un micronutriente esencial en varios procesos metabólicos en animales y humanos. La deficiencia de selenio se ha relacionado con una predisposición a desarrollar enfermedades como cáncer, diabetes, enfermedades cardiovasculares, entre otras. Em química médica, el selenio ha ganado importancia desde el descubrimiento del ebselen, etaselen y difenil diselenide. Objetivo: Esta revisión tiene como objetivo recopilar los principales datos disponibles en la literatura sobre la importancia del selenio para la vida humana, y proporcionar al lector una descripción general del papel biológico de este elemento, las principales enfermedades relacionadas con la deficiencia de este elemento, así como los compuestos de organoselenio más destacados. Metodología: Se recuperaron artículos y tesis académicas que contemplaban el papel del selenio en la bioquímica y la química médica, publicados en portugués e inglés, utilizando las bases de datos SciFinder, PubMed y Google Scholar. Resultados: Hasta el momento, se han identificado 25 selenoproteínas que realizan funciones biológicas esenciales en animales y humanos. Se sabe que la deficiencia de selenio está directamente relacionada con la predisposición en el desarrollo de varias dolencias, y también es la principal causa de enfermedades como las de Keshan y Kashin-Beck. En el campo de la química médica se ha comprobado que es posible desarrollar moléculas bioactivas, de baja toxicidad, que contengan átomos de selenio en su estructura. Conclusión: El selenio es un elemento esencial en la vida, siendo un componente central de las selenoproteínas. Comprender los procesos bioquímicos modulados por ellos es imperativo para que los químicos médicos puedan desarrollar fármacos potentes que contengan átomos de selenio en su estructura.
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For over 60 years, selenium (Se) has been known as an essential microelement to many biological functions, including cardiovascular homeostasis. This review presents a compilation of studies conducted in the past 20 years related to chronic Chagas disease cardiomyopathy (CCC), caused by Trypanosoma cruzi infection, a neglected disease that represents a global burden, especially in Latin America. Experimental and clinical data indicate that Se may be used as a complementary therapy to prevent heart failure and improve heart function. Starting from the main questions "Is Se deficiency related to heart inflammation and arrhythmogenesis in CCC?" and "Could Se be recommended as a therapeutic strategy for CCC?", we show evidence implicating the complex and multidetermined CCC physiopathology, discussing its possible interplays with the multifunctional cytokine TGF-ß as regulators of immune response and fibrosis. We present two new proposals to face this global public health challenge in vulnerable populations affected by this parasitic disease: fibrosis modulation mediated by TGF-ß pathways and the possible use of selenoproteins as antioxidants regulating the increased reactive oxygen stress present in CCC inflammatory environments. We assess the opportunity to consider the beneficial effects of Se in preventing heart failure as a concept to be applied for CCC patients.
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Doença de Chagas , Doenças Transmissíveis , Insuficiência Cardíaca , Selênio , Trypanosoma cruzi , Doença de Chagas/tratamento farmacológico , Doença de Chagas/parasitologia , Fibrose , Humanos , Selênio/uso terapêutico , Fator de Crescimento Transformador beta , Trypanosoma cruzi/fisiologiaRESUMO
Se is an essential element in mammals. We review how its bioavailability in soil and the ability of plants to accumulate Se in foods depends on the soil Se profile (including levels and formats), besides to describe how the various selenoproteins have important biochemical functions in the body and directly impact human health. Owing to its favorable characteristics, the scientific community has investigated selenomethionine in most nut matrices. Among nuts, Brazil nuts have been highlighted as one of the richest sources of bioavailable Se. We summarize the most commonly used analytical methods for Se species and total Se determination in nuts. We also discuss the chemical forms of Se metabolized by mammals, human biochemistry and health outcomes from daily dietary intake of Se from Brazil nuts. These findings may facilitate the understanding of the importance of adequate dietary Se intake and enable researchers to define methods to determine Se species.
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Bertholletia , Selênio , Humanos , Nozes , Avaliação de Resultados em Cuidados de Saúde , SelenoproteínasRESUMO
Several single nucleotide polymorphisms (SNPs) could indirectly, as well directly, influence metabolic parameters related to health effects in response to selenium (Se) supplementation. This study aimed to investigate whether the selenoprotein SNPs were associated with the response of Se status biomarkers to the Brazil nut consumption in patients using statins and if the variation in Se homoeostasis could affect antioxidant protection, lipid profile, muscle homoeostasis and selenoproteins mRNA. The study was performed in the Ribeirão Preto Medical School University Hospital. Thirty-two patients using statins received one unit of Brazil nut daily for 3 months. Body composition, blood Se concentrations, erythrocyte glutathione peroxidase (GPX) activity, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triacylglycerol (TAG), creatine kinase (CK) activity and gene expression of GPX1 and selenoprotein P (SELENOP) were evaluated before and after Brazil nut consumption. The volunteers were genotyped for SNP in GPX1 (rs1050450) and SELENOP (rs3877899 and rs7579). SNPs in selenoproteins were not associated with plasma and erythrocyte Se, but SNPs in SELENOP influenced the response of erythrocyte GPX activity and CK activity, TAG and LDL after Brazil nut consumption. Also, Brazil nut consumption increased GPX1 mRNA expression only in subjects with rs1050450 CC genotype. SELENOP mRNA expression was significantly lower in subjects with rs7579 GG genotype before and after the intervention. Thus, SNP in SELENOP could be associated with interindividual differences in Se homeostasis after Brazil nut consumption, emphasising the involvement of genetic variability in response to Se consumption towards health maintenance and disease prevention.
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Bertholletia , Inibidores de Hidroximetilglutaril-CoA Redutases , Selênio , Antioxidantes , Biomarcadores , Glutationa Peroxidase/metabolismo , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , RNA Mensageiro/genética , Selenoproteína P/genética , Selenoproteínas/genética , TriglicerídeosRESUMO
This review covers current knowledge of selenium in the dietary intake, its bioavailability, metabolism, functions, biomarkers, supplementation and toxicity, as well as its relationship with diseases and gut microbiota specifically on the symbiotic relationship between gut microflora and selenium status. Selenium is essential for the maintenance of the immune system, conversion of thyroid hormones, protection against the harmful action of heavy metals and xenobiotics as well as for the reduction of the risk of chronic diseases. Selenium is able to balance the microbial flora avoiding health damage associated with dysbiosis. Experimental studies have shown that inorganic and organic selenocompounds are metabolized to selenomethionine and incorporated by bacteria from the gut microflora, therefore highlighting their role in improving the bioavailability of selenocompounds. Dietary selenium can affect the gut microbial colonization, which in turn influences the host's selenium status and expression of selenoproteoma. Selenium deficiency may result in a phenotype of gut microbiota that is more susceptible to cancer, thyroid dysfunctions, inflammatory bowel disease, and cardiovascular disorders. Although the host and gut microbiota benefit each other from their symbiotic relationship, they may become competitors if the supply of micronutrients is limited. Intestinal bacteria can remove selenium from the host resulting in two to three times lower levels of host's selenoproteins under selenium-limiting conditions. There are still gaps in whether these consequences are unfavorable to humans and animals or whether the daily intake of selenium is also adapted to meet the needs of the bacteria.
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Selenium (Se) is an essential micronutrient for human biology that executes its functions as the amino acid selenocysteine via selenoproteins, which have important functions in, for example, antioxidation, immunomodulation, thyroid metabolism, and human fertility. Se nutritional status is assessed using the quantification of blood Se biomarkers, which are influenced by several factors, including diet, age, gender, smoking status, alcohol consumption, health condition, and the genetic characteristics of individuals. Nutrigenetic studies have identified single nucleotide polymorphisms in selenoproteins that might clarify the high variability in values reported for biomarkers of Se nutritional status in different populations, and the response of these biomarkers to Se supplementation with either organic or inorganic forms of Se. This review aims to (1) define the basic aspects of Se biology, (2) describe the current most commonly used biomarkers of Se nutritional status, and (3) provide a summary of associations between functional single nucleotide polymorphisms in selenoproteins and biomarkers of Se status in healthy populations.
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Selênio , Biomarcadores , Humanos , Nutrigenômica , Estado Nutricional , Selenoproteínas/genéticaRESUMO
Rheumatoid arthritis (RA) is an autoimmune and inflammatory disease that can cause joint damage. Among the environmental risk factors, diet plays an important role because it can aggravate or attenuate inflammation. Selenium (Se) is considered an essential trace element since it is a structural component of antioxidant enzymes; however, its concentration can be affected by diet, drugs and genetic polymorphisms. Studies have reported that RA patients have a deficient diet in some food groups that is associated with parameters of disease activity. Furthermore, it has been shown that there is an alteration in serum Se levels in this population. Although some clinical trials have been conducted in the past to analyze the effect of Se supplementation in RA, no significant results were obtained. Contrastingly, experimental studies that have evaluated the effect of novel Se nanoparticles in RA-induced models have shown promising results on the restoration of antioxidant enzyme levels. In particular, glutathione peroxidase (GPx) is an important selenoprotein that could have a modulating effect on inflammation in RA. Considering that RA patients present an inflammatory and oxidative state, the aim of this review is to give an overview of the current knowledge about the relevance of Se status in RA.
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Artrite Reumatoide/sangue , Estado Nutricional , Selênio/deficiência , Oligoelementos/deficiência , Animais , Antioxidantes/análise , Artrite Reumatoide/complicações , Dieta/efeitos adversos , Dieta Saudável/métodos , Suplementos Nutricionais , Glutationa Peroxidase/análise , Humanos , Inflamação , Oxirredução/efeitos dos fármacos , Selênio/sangue , Selenoproteínas/análise , Oligoelementos/sangueRESUMO
BACKGROUND & AIMS: Although the mechanisms by which statins promote muscle disorders remain unclear, supplementation with dietary antioxidants may mitigate statins' side effects. This study aimed to investigate whether the consumption of Brazil nuts modulates serum creatine kinase (CK) activity in patients regularly using statins. METHODS: The study was performed in the Ribeirão Preto Medical School University Hospital. Thirty-two patients in regular use of statins were divided according to CK activity levels (G1: increased or G2: normal) and received one unit of Brazil nut daily for 3 months. Body composition, blood selenium (Se) concentrations, erythrocyte glutathione peroxidase (GPX) activity, oxidative stress parameters, and CK activity were evaluated before and after supplementation. RESULTS: In both groups, supplementation with one Brazil nut daily for 3 months contributed to achieve decreased levels of CK activity in serum, with positive changes in plasma and erythrocyte Se concentrations (p < 0.0001), and increased levels of GPX activity. Among the parameters related to curbing of oxidative stress, we observed reduced levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in both groups after supplementation. We also found a moderately negative association between CK and GPX activity (r = -41; p < 0.02). Expression of selenoproteins GPX1, SELENOP, and SELENON after Brazil nut supplementation was unchanged. CONCLUSION: Brazil nut consumption enhanced the control of CK activity by improving oxidative stress biomarkers in patients using statins but did not modulate mRNA expression of selenoproteins.
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Bertholletia , Creatina Quinase/sangue , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Nozes , Estresse Oxidativo/efeitos dos fármacos , RNA Mensageiro/genética , Selenoproteínas/genética , Adolescente , Adulto , Biomarcadores/sangue , Brasil , Feminino , Regulação da Expressão Gênica , Glutationa Peroxidase/sangue , Glutationa Peroxidase/genética , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Masculino , Pessoa de Meia-Idade , Proteínas Musculares/sangue , Proteínas Musculares/genética , RNA Mensageiro/sangue , Selenoproteína P/sangue , Selenoproteína P/genética , Selenoproteínas/sangue , Fatores de Tempo , Adulto Jovem , Glutationa Peroxidase GPX1RESUMO
BACKGROUND: Selenoproteins are selenocysteine (Sec)-containing proteins that exhibit numerous physiological functions, mainly antioxidative activities. Studies have suggested that several human selenoproteins play an important role in tumor initiation and progression, including melanoma. METHODS: Using RNA-seq data set from Sequence Reads Archive (SRA) experiments published at the National Center for Biotechnology Information (NCBI), we determined and compared the transcriptional levels of the 25 selenoproteins-coding sequences found in 16 human-derived melanoma cell lines and compared to four melanocyte controls. RESULTS: 15 selenoprotein-coding genes were found to be expressed in melanoma and normal melanocyte cells, and their mRNA levels varied among the cell lines. All melanoma cells analyzed with BRAF or NRAS mutations presented upregulated levels of SELENOI, TXNRD1, and SELENOT transcripts and downregulated levels of SELENOW and SELENON transcripts in comparison with melanocytes controls. Moreover, SELENOW, SELENON, SELENOI, TXNRD1, and SELENOT-coding transcripts were affected when BRAF-mutated A375 cells were treated with CPI203, A771726 or Vorinostat drugs. CONCLUSION: Our results indicate that melanoma cells can modify, in a different manner, the selenoprotein transcript levels, as a possible mechanism to control tumor progression. We suggest that the usage of diet and supplements containing selenium should be carefully used for patients with melanoma.
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Selenoproteínas/genética , Neoplasias Cutâneas/genética , Tiorredoxina Redutase 1/genética , Transcrição Gênica/genética , Linhagem Celular Tumoral , Humanos , Melanócitos/patologia , Melanoma/patologia , Selenoproteínas/metabolismo , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Tiorredoxina Redutase 1/metabolismoRESUMO
Selenium and selenoproteins are important components of living organisms that play a role in different biological processes. Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) is a powerful analytical technique that has been employed to obtain distribution maps of selenium in biological tissues in a direct manner, as well as in selenoproteins, previously separated by their molecular masses and isoelectric points using two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). In this chapter, we present the protocols to perform LA-ICP-MS imaging experiments, allowing the distribution visualization and determination of selenium and/or selenoproteins in biological systems.
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Eletroforese em Gel Bidimensional , Imagem Molecular/métodos , Selênio , Selenoproteínas/análise , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Eletroforese em Gel Bidimensional/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodosRESUMO
The antagonism of mercury toxicity by selenium has been well documented. Mercury is a toxic metal, widespread in the environment. The main target organs (kidneys, lungs, or brain) of mercury vary depending on its chemical forms (inorganic or organic). Selenium is a semimetal essential to mammalian life as part of the amino acid selenocysteine, which is required to the synthesis of the selenoproteins. This chapter has the aim of disclosing the role of selenide or hydrogen selenide (Se-2 or HSe-) as central metabolite of selenium and as an important antidote of the electrophilic mercury forms (particularly, Hg2+ and MeHg). Emphasis will be centered on the neurotoxicity of electrophile forms of mercury and selenium. The controversial participation of electrophile mercury and selenium forms in the development of some neurodegenerative disease will be briefly presented. The potential pharmacological use of organoseleno compounds (Ebselen and diphenyl diselenide) in the treatment of mercury poisoning will be considered. The central role of thiol (-SH) and selenol (-SeH) groups as the generic targets of electrophile mercury forms and the need of new in silico tools to guide the future biological researches will be commented.
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Encéfalo/metabolismo , Intoxicação do Sistema Nervoso por Mercúrio/metabolismo , Síndromes Neurotóxicas/etiologia , Selênio/intoxicação , Antídotos/uso terapêutico , Azóis/uso terapêutico , Derivados de Benzeno/uso terapêutico , Humanos , Isoindóis , Intoxicação por Mercúrio/tratamento farmacológico , Intoxicação por Mercúrio/metabolismo , Intoxicação do Sistema Nervoso por Mercúrio/tratamento farmacológico , Síndromes Neurotóxicas/tratamento farmacológico , Síndromes Neurotóxicas/metabolismo , Compostos Organosselênicos/uso terapêutico , Selenoproteínas/metabolismoRESUMO
Superoxide-hydrogen peroxide (S-HP) imbalance genetically caused by a gene polymorphism in the human manganese superoxide dismutase enzyme (Val16Ala-MnSOD) is associated with several diseases. Into mitochondria, MnSOD catalyses superoxide radical producing HP and oxygen. Ala-MnSOD genotype presents a high MnSOD efficiency and generates the highest HP concentrations that has been associated with the risk of several cancer types. Cellular selenoenzymes glutathione peroxidase and thioredoxin reductase (TrxR) and catalase (CAT) are essential to HP removal produced in excess in cells. Since, synthesis and activities of selenoenzymes are selenium dependent, we hypothesized that AA-MnSOD cells could have an improvement on antioxidant status undergoing Seleno-L-methionine (SeMet) treatment. This study performed an in vitro protocol to evaluate the response of peripheral blood mononuclear cells (PBMC) carriers of different Val16Ala-MnSOD genotypes exposed to SeMet. SeMet effects on cell viability, apoptosis induction and modulation of oxidative variables were determined using spectrophotometric, flow cytometry, fluorimetric and immunoassays. Gene modulation of antioxidant enzymes was also performed by qRT-PCR. From an initial protocol using heterozygous (AV) cells was determined that 1nM SeMet presented a cytoprotective effect. However, whereas this concentration did not change AA viability, in VV cells it was cytotoxic by increasing necrosis events. SeMet induced higher selenoenzymes levels in AA and VV cells and decreased oxidative markers levels including DNA damage. The results suggest a pharmacogenetic positive response of SeMet effect on AA-cells. Future studies in vivo could be essential to evaluate the potential clinical impact of S-HP imbalance after use of foods or supplements containing SeMet.
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Peróxido de Hidrogênio/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Polimorfismo Genético , Selenometionina/farmacologia , Superóxido Dismutase/genética , Superóxidos/metabolismo , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Humanos , Leucócitos Mononucleares/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Selenometionina/administração & dosagem , Relação Estrutura-Atividade , Superóxido Dismutase/metabolismoRESUMO
Selenoproteins (Sels) are involved in oxidative stress regulation. Glutathione peroxidase (GPx) and thioredoxin reductase are among the most studied Sels in crustaceans. Since their expressions and activities are affected by pathogens, environmental and metabolic factors, their functions might be key factors to orchestrate the redox cellular balance. The most studied invertebrate selenoproteome is from Drosophila. In this fly, SelD and SelB are involved in selenoproteins synthesis, whereas SelBthD, SelH and SelK are associated with embryogenesis and animal viability. None of the Sels found in Drosophila have been identified in marine crustaceans yet, and their discovery and function identification is an interesting research challenge. SelM has been identified in crustaceans and is differentially expressed in tissues, while its function remains to be clarified. SelW and G-rich Sel were recently discovered in marine crustaceans and their functions are yet to be clearly defined. To fully understand the crustacean selenoproteome, it is still necessary to identify important Sels such as the SelD, SelBthD and SelB homologs. This knowledge can also be useful for marine crustacean industry to propose better culture strategies, enhanced health and improved profits.
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Animais , Crustáceos , Oxirredução , Selenoproteínas , Artrópodes , InvertebradosRESUMO
Evidências têm demonstrado que distúrbios do metabolismo são comuns em células tumorais, levando ao aumento do estresse oxidativo. A elevação na produção de espécies reativas de oxigênio (EROs) associada à baixa atividade antioxidante tem sido relacionada a vários tipos de câncer. O selênio, micronutriente antioxidante, pode funcionar como um agente antimutagênico, prevenindo transformações malignas de células normais. Realizou-se um levantamento bibliográfico no período 2000 a 2009 mediante consulta à base de dados PubMed (National Library of Medicine´s Medline Biomedical Literature, USA), selecionando-se 39 artigos que avaliaram a relação entre câncer, estresse oxidativo e suplementação com selênio. O efeito protetor desse mineral é especialmente associado à sua presença na glutationa peroxidase e na tioredoxina redutase, enzimas protetoras do DNA e outros componentes celulares contra o dano oxidativo causado pelas EROs. Vários estudos têm demonstrado a expressão reduzida destas enzimas em diversos tipos de câncer, principalmente quando associados a uma baixa ingestão de selênio, que pode acentuar os danos causados. A suplementação de selênio parece ocasionar redução do risco de alguns tipos de câncer diminuindo o estresse oxidativo e o dano ao DNA. No entanto, mais estudos são necessários para esclarecer as doses de selênio adequadas para cada situação (sexo, localização geográfica e tipo de câncer).
There are evidences that metabolic disorders are common in tumoral cells, leading to increased oxidative stress. The rising in the production of reactive oxygen species associated to low antioxidant activity have been associated to different types of cancer. Selenium, an antioxidant micronutrient can work as an anti-cancer agent preventing malignant modification in healthy cells. A literature review was carried out in the period 2000-2009 in the database PubMed selecting 39 articles which assessed the relationship between cancer, oxidative stress, and supplementation with selenium. The protective effect of selenium is specially associated to the presence of glutathione peroxidase and of thioredoxin reductase enzymes and with other cell components which protect the tissues against the oxidative damage caused by reactive oxygen species - ROS. Several studies have shown a decrease of these enzymes in many types of cancer, mainly when associated with low selenium consumption, increasing the damage caused by ROS. Selenium supplementation seems to reduce the risk of some types of cancer by stress oxidative reduction and by limiting the damage to DNA. Nevertheless, more studies are necessary to clarify the adequate selenium doses in each situation (gender, geographic localization and type of cancer).
Assuntos
Humanos , Antioxidantes/administração & dosagem , Neoplasias/metabolismo , Selênio/administração & dosagem , Selenoproteínas/fisiologia , Dano ao DNA , Glutationa Peroxidase/metabolismo , Neoplasias/enzimologia , Neoplasias/prevenção & controle , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Tiorredoxina Dissulfeto Redutase/metabolismoRESUMO
El selenio (Se) es un mineral esencial en la nutrición animal y se considera su participación en diversos procesos asociados a la producción animal, tan diversos como la fertilidad de la especie y la prevención de enfermedades. Laglutatión-peroxidasa (GSH-Px), fue la primera enzima en que se demostró la presencia activa del selenio y su importancia al evitar el daño oxidativo de las membranas celulares. Con anterioridad se había demostrado que la conocida como Enfermedad del músculo blanco era consecuencia de la deficiencia de Se, determinando muerte en animales recién nacidos y ocasionalmente en animales en desarrollo y aún en adultos, en particular en rumiantes. Actualmente ha quedado claro que el Se también es crítico en la estructuración de las enzimas necesarias para la síntesis de la hormona tiroidea y para su activaciónen los tejidos periféricos, pasando de T4 a T3. La deficiencia de Se afecta seriamente la capacidad de respuesta inmune de los animales. El diagnóstico de la deficiencia debe fundamentarse en los niveles del elemento en los suelos, las plantas forrajeras y la condición del animal en sangre y tejidos. Se han instrumentado diversas formas de suplementación del elemento que pueden emplearse dependiendo de las condiciones productivas de los animales y sus niveles previos de Se. La intoxicación por Se (Selenosis) debe tenerse en cuenta en los programas de suplementación, y puede ocurrir en formas crónicas o agudas. Las formas crónicas ocurren en regiones con suelos ricos en el elemento y condiciones que favorecen su absorción por las plantas forrajeras. Las formas agudas generalmente ocurren por excesos del elemento en las dietas o las sales que se administran a los animales o por errores de dosificación en las formulaciones parenterales. La relación metabólica del Se entre la hembra gestante, el feto y el recién nacido, es un área que requiere mayor investigación.
O selênio (Se) é um mineral essencial na nutrição animal e se considera sua participação em diversos processos associados à produção animal, tão diversos como na fertilidade das espécies e prevenção de enfermidades. A glutation peroxidase (GSH-Px), foi a primeira enzima em que se demonstrou a presença ativa do selênio e sua importância para evitar o dano oxidativo nas membranas celulares. Anteriormente sabia-se que a enfermidade do músculo branco era conseqüência da deficiência de Se, determinando a morte em animais recém-nascidos e ocasionalmente em animais em desenvolvimento, animais adultos e em particular em ruminantes. Atualmente, está claro que o Se é crítico na estruturação das enzimas necessáriaspara a síntese de hormônios da tireóide e para sua ativação nos tecidos periféricos, passando de T3 a T4. A deficiência de Se afeta seriamente a capacidade da resposta imune dos animais. O diagnóstico da deficiência deve fundamentar-se nos níveis deste elemento no solo, nas plantas forrageiras e nas condições do animal. Indicam-se diversas formas de suplementação deste elemento, que podem ser empregadas dependendo das condições produtivas dos animais e seus níveis prévios de Se. As intoxicações por Se (selenose), devem ser consideradas nos programas de suplementação, que pode ocorrer de forma crônica ou aguda. As formas crônicas ocorrem em regiões com solos ricos no elemento e nas condições que favorecem a absorção pelas plantas forrageiras. As formas agudas geralmente ocorrem por excesso do elemento nas dietas, ou sais administrados aos animais ou por erros na dosagem das formulações parenterais. A relação metabólica do Se na fêmea gestante, o feto e orecém-nascido, é uma área que requer uma maior investigação.
Selenium (Se) is an essential trace element for animal nutrition and plays multiple actions related to animal production, fertility and prevention of diseases. Glutathione peroxidase enzyme (GSH-Px) was the first seleno enzyme to demonstrate the active presence of selenium and its importance to prevent cellular membrane oxidative damage. Formerly, White muscle disease (WMD) was recognized as resulting from Se deficiency, determining new born mortality and adult animals, especially in ruminants. Nowadays, it is clear that Se is critical for thyroid hormone synthesis and its activation in peripheral tissues from T3 to T4. Lack of Se seriously affects the capacity of immune response by the animals. Se status in the soil, plants, animal blood and tissues can be used as a tool to diagnose Se deficiency. Several forms of Se supplementation are described which can be applied depending of the productive capacity of the animals and their previous levels of Se. Acute and chronic Se intoxication (Selenosis) should be considered in supplementation programs as it may occur in a chronic or acute way. Chronic forms are associated to regional seleniferous soils, with permanent or repeated consumption of seleniferous plants. Acute forms are associated with high ingestion of Se as a result of wrongly designed diets, salt provided to the animals or parenteral injection dosage mistakes. The metabolic relation among Se, the fetus, the newborn and the pregnant dam requires further investigations.