Selênio, um elemento essencial à vida humana

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.

Research advance of biological functions of selenium and selenoprotein in ocular diseases / 国际眼科杂志(Guoji Yanke Zazhi)

@#Selenium is an essential microelement required as a nutrient by human organism to perform important biological functions, mainly in the form of selenocysteine. It plays an important role in improving human immunity and the myocardial nutritional blood flow, and preventing oxidative stress. Various ocular diseases are closely associated with selenium and selenoprotein due to the presence of high concentration of selenium. This article mainly aims to review the present research advance of biological functions of selenium and selenoprotein in ocular diseases, and provide some valuable reference for deeper study of selenium in human eyes.

Analysis on association between single nucleotide polymorphism of selenoprotein S gene and risk of liver cancer / 吉林大学学报(医学版)

Objective: To investigate the distribution of single nucleotide polymorphism (SNP) of selenoprotein S (SelS) gene in the patients with liver cancer and the healthy controls, and to clarify the correlation of the SNP and the risk of liver cancer in the Inner Mongolia Han population. Methods: The distribution of genotypic and allelic frequencies at rs34743744 site was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method among 96 patients with liver cancer and 435 healthy controls, and verified by gene sequencing analysis. The relationship between SNP of SelS gene and the risk of liver cancer was analyzed. Results: There were no differences of the frequencies of CC, CT, and TT genotypes and C and T alleles at rs34713741 site of SelS gene between the patients with liver cancer and the healthy controls(χ=2 679, χ =2. 334, P>0. 05). The differences in the frequencies of CC, CT, and TT genotypes and C and T alleles at rs34743744 site of SelS gene of the drinkers between liver cancer group and healthy control group were significant (χ = 6. 533, χ = 6.447, P<0.05). The relative risk of liver cancer in the drinkers carrying T allele was 2. 297 times of the drinkers carrying genotype CC (OR = 2.297, 95% CI: 4.202 - 4.393). Conclusion: The gene-environment interaction of SelS and drinking may associate with liver cancer in the Inner Mongolia Han population.

Effects of oxidative damage on selenoprotein gene expression in articular chondrocytes and the mechanism of selenium / 中华地方病学杂志

Objective To explore the effects of oxidative damage and selenium on the apoptosis of articular chondrocytes and the expression of selenoprotein genes.Methods C28/I2 chondrocytes were preincubated for 24 h,using sodium selenite (Na2SeO3) or t-butyl hydroperoxide (tBHP) for 24 h.The experiment was divided into six groups,including control group (C,0.00 mg/L Na2,SeO3 + 0.00 μmol/L tBHP),selenium beforehand protection group (S2,0.10 mg/L Na2SeO3),oxidative damage group (O,150.00 μmol/L tBHP),low dose selenium protection group (OS 1,0.05mg/L Na2SeO3 + 150.00 μmol/L tBHP),medium dose selenium protection group (OS2,0.10 mg/L Na2SeO3 + 150.00 μmol/L tBHP),and high dose selenium protection group (OS3,0.15 mg/L Na2SeO3 + 150.00 μmol/L tBHP).After 24 h,Hoechst 33342 staining method was used to observe apoptosis,mRNA expression of glutathione peroxidase 1 (GPX1),GPX4,deiodinase 2 (DIO2),DIO3,selenoprotein P (SEPP1),thioredoxin reductase 1 (TrxR-1) and selenoprotein W(Sel W) was detected by Real-time PCR,both experiments were done three times.Results Apoptotic rates of C,S2,O,OS1,OS2,OS3 groups [(0.78 ± 0.06)％,(13.61 ± 7.11)％,(92.27 ± 3.44)％,(71.38 ± 5.22)％,(44.31 ± 9.16)％,(72.46 ± 4.69)％] were compared between groups,the differences were statistically significant (F =120.10,P ＜ 0.01).The apoptotic rates of O group was significantly higher than that of C group (P ＜ 0.05);compared to O group,the apoptotic rates of OS1,OS2,OS3 groups decreased significantly (P＜ 0.05),OS2 group was the most obvious.DIO2,SEPP1,GPX1,GPX4,TrxR-1,Sel W mRNA levels were compared in the six groups,the differences were statistically significant (F =24.60,14.53,127.60,30.60,637.10,59.64,P ＜ 0.01).Compared to C group (1.00 ± 0.00),the mRNA levels of GPX1 (0.10 ± 0.05),GPX4 (0.43 ± 0.09),TrxR-1 (0.11 ± 0.05) and Sel W (0.72 ± 0.15) in O groups were decreased significantly (P ＜ 0.05);compared to 0 group,the mRNA levels of GPX1 in OS1 (0.20 ± 0.03),OS2 (0.74 ± 0.10),and OS3 (0.30 ± 0.07) were increased significantly (P ＜ 0.05).Conclusion Down-regulated expression of selenoprotein genes are involved in the regulation process of articular cartilage apoptosis caused by oxidative stress,selenium also has a regulatory role in selenoprotein gene expression in articular chondrocytes.

Effects of oxidative damage on selenoprotein gene expression in articular chondrocytes and the mechanism of selenium / 中华地方病学杂志

Objective To explore the effects of oxidative damage and selenium on the apoptosis of articular chondrocytes and the expression of selenoprotein genes.Methods C28/I2 chondrocytes were preincubated for 24 h,using sodium selenite (Na2SeO3) or t-butyl hydroperoxide (tBHP) for 24 h.The experiment was divided into six groups,including control group (C,0.00 mg/L Na2,SeO3 + 0.00 μmol/L tBHP),selenium beforehand protection group (S2,0.10 mg/L Na2SeO3),oxidative damage group (O,150.00 μmol/L tBHP),low dose selenium protection group (OS 1,0.05mg/L Na2SeO3 + 150.00 μmol/L tBHP),medium dose selenium protection group (OS2,0.10 mg/L Na2SeO3 + 150.00 μmol/L tBHP),and high dose selenium protection group (OS3,0.15 mg/L Na2SeO3 + 150.00 μmol/L tBHP).After 24 h,Hoechst 33342 staining method was used to observe apoptosis,mRNA expression of glutathione peroxidase 1 (GPX1),GPX4,deiodinase 2 (DIO2),DIO3,selenoprotein P (SEPP1),thioredoxin reductase 1 (TrxR-1) and selenoprotein W(Sel W) was detected by Real-time PCR,both experiments were done three times.Results Apoptotic rates of C,S2,O,OS1,OS2,OS3 groups [(0.78 ± 0.06)％,(13.61 ± 7.11)％,(92.27 ± 3.44)％,(71.38 ± 5.22)％,(44.31 ± 9.16)％,(72.46 ± 4.69)％] were compared between groups,the differences were statistically significant (F =120.10,P ＜ 0.01).The apoptotic rates of O group was significantly higher than that of C group (P ＜ 0.05);compared to O group,the apoptotic rates of OS1,OS2,OS3 groups decreased significantly (P＜ 0.05),OS2 group was the most obvious.DIO2,SEPP1,GPX1,GPX4,TrxR-1,Sel W mRNA levels were compared in the six groups,the differences were statistically significant (F =24.60,14.53,127.60,30.60,637.10,59.64,P ＜ 0.01).Compared to C group (1.00 ± 0.00),the mRNA levels of GPX1 (0.10 ± 0.05),GPX4 (0.43 ± 0.09),TrxR-1 (0.11 ± 0.05) and Sel W (0.72 ± 0.15) in O groups were decreased significantly (P ＜ 0.05);compared to 0 group,the mRNA levels of GPX1 in OS1 (0.20 ± 0.03),OS2 (0.74 ± 0.10),and OS3 (0.30 ± 0.07) were increased significantly (P ＜ 0.05).Conclusion Down-regulated expression of selenoprotein genes are involved in the regulation process of articular cartilage apoptosis caused by oxidative stress,selenium also has a regulatory role in selenoprotein gene expression in articular chondrocytes.

The crustacean selenoproteome similarity to other arthropods homologs: a mini review

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.

Effect of selenium, protein and vitamin E deficiency on mRNA expression of rat cardiac selenoprotein / 中国地方病学杂志

ObjectiveTo explore the effect of selenium,protein and vitamin E deficiency on mRNA expression of rat cardiac selenoprotein,and their relation with myocardial injury.MethodsForty male Wistar rats were randomly divided into 4 groups:low selenium low protein low vitamin E group(group A),low selenium low protein adequate vitamin E group(group B),adequate selenium adequate protein low vitamin E group(group C),and adequate selenium adequate protein adequate vitamin E group (group D),10 rats in each group.The activity of whole blood glùtathione peroxidase(GSH-Px ) was measured using dithiobis nitrobenzoic acid (DTNB) at the end of sixth month experiment.The levels of mRNA expression of glutathione peroxidase 1(Gpx1),phospholipid hydroperoxide glutathione peroxidase 4(Gpx4),thioredoxin reductase(TrxR),selenoprotein P(Se-P) and selenoprotein W(Se-W) were determined by real-time fluorescence quantitative PCR at the end of sixth month.Histopathological changes of myocardial injury were observed with light microscope.ResultsThe activity of GSH-Px was (44.6 ± 3.1 ),(45.5 ± 1.6),(86.6 ± 2.2),(85.6 ± 1.2)U/L,respectively,in the above four groups at the end of sixth month,and the difference was statistically significant(F =100.7,P ＜ 0.01 ) ; the activity of GSH-Px of groups C and D was higher than that of groups A,B(all P ＜ 0.05).mRNA expression of myocardial tissue of the four groups was as follows,Gpx1(0.099 ± 0.312,0.054 ± 0.007,0.386 ± 0.067,0.340 ± 0.085),Gpx4(1.005 ± 0.089,0.810 ± 0.229,0.895 ± 0.084,0.922 ± 0.399),and Se-W(0.188 ± 0.080,0.119 ± 0.069,0.574 ± 0.167,0.570 ± 0.383),and the difference was statistically significant(F =112.1,3.76,22.8,all P ＜ 0.05) ; the mRNA levels of Gpx1,Se-W of groups C,D were significantly higher than that of groups A,B(all P ＜ 0.05).The mRNA expression of Gpx4 of group A was higher than that of group C(P ＜ 0.05).The mRNA expression of TrxR(0.130 ± 0.037,0.127 ± 0.038,0.134 ± 0.021,0.120 ± 0.014) and Se-P(0.446 ± 0.155,0.413 ± 0.152,0.385 ± 0.041,0.408 ±0.208 ) was not statistically different among the four groups (F =0.91,1.75,all P ＞ 0.05).Pathological changes of myocardial tissue were mainly as foci of coagulative necrosis.The necrosis detection rate of the four groups was 8/10,4/9,2/10,and 1/10,respectively,and the difference was significant statistically(Fisher exact test,P =0.0067).ConclusionsLong-term selenium,protein and vitamin E deficiency will reduce body antioxidant capacity and lead to myocardial injury.The mRNA levels of Gpx1 and Se-W and selenium level are closely related.The mRNA levels of Gpx4,TrxR and Se-P remain relatively stable.

O papel das selenoproteínas no câncer / The role of selenoproteins in cancer

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).

Selenio y salud animal Importancia, deficiencia, suplementación y toxicidad / Selenium and animal health: importance, defficiency, supplementation and toxicity / Selênio e saúde animal importância, deficiência, suplementação e toxidez

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.