RESUMO
Here, we addressed the pharmacology and toxicology of synthetic organoselenium compounds and some naturally occurring organoselenium amino acids. The use of selenium as a tool in organic synthesis and as a pharmacological agent goes back to the middle of the nineteenth and the beginning of the twentieth centuries. The rediscovery of ebselen and its investigation in clinical trials have motivated the search for new organoselenium molecules with pharmacological properties. Although ebselen and diselenides have some overlapping pharmacological properties, their molecular targets are not identical. However, they have similar anti-inflammatory and antioxidant activities, possibly, via activation of transcription factors, regulating the expression of antioxidant genes. In short, our knowledge about the pharmacological properties of simple organoselenium compounds is still elusive. However, contrary to our early expectations that they could imitate selenoproteins, organoselenium compounds seem to have non-specific modulatory activation of antioxidant pathways and specific inhibitory effects in some thiol-containing proteins. The thiol-oxidizing properties of organoselenium compounds are considered the molecular basis of their chronic toxicity; however, the acute use of organoselenium compounds as inhibitors of specific thiol-containing enzymes can be of therapeutic significance. In summary, the outcomes of the clinical trials of ebselen as a mimetic of lithium or as an inhibitor of SARS-CoV-2 proteases will be important to the field of organoselenium synthesis. The development of computational techniques that could predict rational modifications in the structure of organoselenium compounds to increase their specificity is required to construct a library of thiol-modifying agents with selectivity toward specific target proteins.
Assuntos
Compostos Organosselênicos/farmacologia , Compostos Organosselênicos/toxicidade , Aminoácidos/química , Animais , Azóis , Humanos , Isoindóis , Estrutura Molecular , Selênio/química , Selênio/fisiologia , Selenoproteínas/química , Compostos de Sulfidrila/químicaRESUMO
The role of the vascular endothelium in inflammation was demonstrated experimentally through biomarkers of endothelial dysfunction and cytoprotection. Selenium is a trace element essential for cell protection against oxidative lesions triggered by reactive oxygen species or inflammatory responses. Preclinical studies have demonstrated a relationship between adhesion molecules as biomarkers of endothelial dysfunction and selenoproteins as biomarkers of selenium status under conditions that mimic different diseases. Most studies in humans indicate an association between selenium deficiency and increased risk of morbidity and mortality, yet the pathophysiology of selenium in endothelial activation remains unknown. Here, we summarize selenium-dependent endothelial function evaluation techniques and focus on the role of selenium in endothelial cytoprotection according to current scientific knowledge. Most studies on the role of selenium in endothelial processes show selenium-dependent endothelial functions and explain how cells and tissues adapt to inflammatory insults. Taken together, these studies show an increase in adhesion molecules and a decrease in the expression of selenoproteins following a decreased exposure to selenium. Few clinical trials have enough methodological quality to be included in meta-analysis on the benefits of selenium supplementation. Furthermore, the methodology adopted in many studies does not consider the relevant findings on the pathophysiology of endothelial dysfunction. Preclinical studies should be more frequently integrated into clinical studies to provide clearer views on the role of selenium status in endothelial cytoprotection.
Assuntos
Citoproteção , Endotélio Vascular/fisiopatologia , Selênio/fisiologia , Selenoproteínas/fisiologia , Endotélio Vascular/metabolismo , Humanos , Oxirredução , Espécies Reativas de Oxigênio/metabolismo , Resultado do TratamentoRESUMO
Parkinson's disease is characterized by the death of dopaminergic neurons, mainly in the substantia nigra, and causes serious locomotor dysfunctions. It is likely that the oxidative damage to cellular biomolecules is among the leading causes of neurodegeneration that occurs in the disease. Selenium is an essential mineral for proper functioning of the brain, and mainly due to its antioxidant activity, it is possible to exert a special role in the prevention and in the nutritional management of Parkinson's disease. Currently, few researchers have investigated the effects of selenium on Parkinson´s disease. However, it is known that very high or very low body levels of selenium can (possibly) contribute to the pathogenesis of Parkinson's disease, because this imbalance results in increased levels of oxidative stress. Therefore, the aim of this work is to review and discuss studies that have addressed these topics and to finally associate the information obtained from them so that these data and associations serve as input to new research.
Assuntos
Estresse Oxidativo , Doença de Parkinson/etiologia , Selênio/fisiologia , Encéfalo/fisiologia , Neurônios Dopaminérgicos/patologia , Humanos , Doença de Parkinson/prevenção & controle , Substância Negra/patologiaRESUMO
Minerals are essential nutrients for the body, are of inorganic nature which gives them the characteristic of being resistant to heat, are involved in a lot of chemical reactions in metabolism, regulating electrolyte balance, in maintaining bone, in the process of blood clotting and the transmission of nerve impulses, particularly its role as enzyme cofactors confers a key role in various physiological processes. Glucose homeostasis involves a fine coordination of events where hormonal control by insulin plays a key role. However, the role of minerals like magnesium, zinc, chromium, iron and selenium in the diabetes is less obvious and in some cases may be controversial. This review shows the knowledge of these five elements and their correlation with diabetes.
Los minerales son nutrientes esenciales para el organismo, de naturaleza inorgánica que les confiere, entre otras características, ser resistentes al calor, participan en diversas reacciones químicas del metabolismo en donde regulan el equilibrio hidroelectrolítico, el mantenimiento óseo, en la trasmisión de los impulsos nerviosos, y durante el proceso de coagulación sanguínea, particularmente por su función como cofactores enzimáticos, tienen un papel clave en varios procesos fisiológicos. La homeostasis de la glucosa involucra una fina coordinación de eventos en donde el control hormonal por la insulina tiene un papel primordial. Sin embargo, la función de los minerales, como el magnesio, el zinc, el cromo, el hierro y el selenio en la diabetes es menos evidente y puede ser, en algún caso, controversial. Esta revisión muestra el conocimiento acerca de estos cinco elementos y su correlación con la diabetes.
Assuntos
Diabetes Mellitus/metabolismo , Micronutrientes/fisiologia , Minerais/metabolismo , Animais , Cromo/deficiência , Cromo/fisiologia , Cromo/uso terapêutico , Diabetes Mellitus Experimental/metabolismo , Glucose/metabolismo , Homeostase , Humanos , Resistência à Insulina , Ferro/fisiologia , Ferro/uso terapêutico , Deficiências de Ferro , Magnésio/fisiologia , Magnésio/uso terapêutico , Deficiência de Magnésio/complicações , Deficiência de Magnésio/metabolismo , Síndrome Metabólica/metabolismo , Micronutrientes/uso terapêutico , Minerais/uso terapêutico , Estresse Oxidativo , Selênio/deficiência , Selênio/fisiologia , Selênio/uso terapêutico , Zinco/deficiência , Zinco/fisiologia , Zinco/uso terapêuticoRESUMO
Deficiencies of nutrients such as amino acids, vitamins, lipids, and trace elements during gestation and early infanthood have strong deleterious effects on the development of the limbic system; these effects may be irreversible, even when adequate supplementation is provided at later developmental stages. Recent advances in the neurochemistry of biometals are increasingly establishing the roles of the trace elements iron, copper, zinc, and selenium in a variety of cell functions and are providing insight into the repercussions of deficiencies and excesses of these elements on the development of the central nervous system, especially the limbic system. The limbic system comprises diverse areas with high metabolic demands and differential storage of iron, copper, zinc, and selenium. This review summarizes available evidence suggesting the involvement of these trace elements in pathological disorders of the limbic system.
Assuntos
Encefalopatias/etiologia , Sistema Límbico/efeitos dos fármacos , Sistema Límbico/crescimento & desenvolvimento , Oligoelementos/sangue , Oligoelementos/deficiência , Encefalopatias/sangue , Cobre/sangue , Cobre/deficiência , Cobre/fisiologia , Humanos , Ferro/sangue , Ferro/fisiologia , Deficiências de Ferro , Sistema Límbico/fisiologia , Fenômenos Fisiológicos da Nutrição/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição/fisiologia , Necessidades Nutricionais , Selênio/sangue , Selênio/deficiência , Selênio/fisiologia , Zinco/sangue , Zinco/deficiência , Zinco/fisiologiaRESUMO
Material y Métodos: Marasmo sin edema y kwashiorkor son manifestaciones de la malnutrición severa, la fisiopatología de estas entidades es todavía poco conocida. En la malnutrición severa se han estimado el yodo, zinc, cobre etc. Y en este trabajo lo hacemos con el selenio. Nosotros medimos el selenio sérico en 90 niños de ambos sexos de 6 a 36 meses de edad de hospitales y guarderías de la ciudad de Quito, 30 niños son normales, 30 niños tienen kwashiorkor y 30 niños tienen marasmo sin edema. Resultados: La concentración sérica de selenio en ug/dl según el estado fue: en el kwashiorkor 2.9+-1.16DE (desviaciones estandar); marasmo sin edema 6.9+-2.12 DE y en los normales 13.9+-5.92DE (KRUSMAL WALLIS H. P 0.001)...
Assuntos
Distúrbios Nutricionais , Selênio/história , Selênio/fisiologiaAssuntos
Antitireóideos/efeitos adversos , Hipotireoidismo Congênito/etiologia , Iodo/deficiência , Selênio/deficiência , Animais , Ásia/epidemiologia , Hipotireoidismo Congênito/classificação , Hipotireoidismo Congênito/epidemiologia , Hipotireoidismo Congênito/fisiopatologia , República Democrática do Congo/epidemiologia , Comportamento Alimentar , Feminino , Doenças Fetais/etiologia , Idade Gestacional , Humanos , Iodo/fisiologia , Troca Materno-Fetal , Modelos Biológicos , Mixedema/epidemiologia , Mixedema/etiologia , Sistema Nervoso/embriologia , Malformações do Sistema Nervoso , Nova Guiné/epidemiologia , Fenótipo , Gravidez , Complicações na Gravidez , Ratos , Selênio/fisiologia , América do Sul/epidemiologia , Glândula Tireoide/embriologia , Glândula Tireoide/fisiopatologia , Hormônios Tireóideos/metabolismo , Tireotropina/metabolismoRESUMO
After a brief discussion of some of the aspects of importance, sources, deficiencies and excesses of selenium the great differences of ingestion between different countries are mentioned. Breast fed children from an area in Venezuela ingest 10 times the amount compared with children from Finland. Among sesame seed samples from 20 different countries used as Se indicators, the highest and the lowest values were found in those of Latin-American origin. With very few exceptions the highest and the lowest urinary and serum Se levels reported in the literature came from this region. The performance of more studies in Latin-America on Se is recommended. Urinary excretion and analysis of finger nails or egg-white of freely foraging hens could be used as suitable indicators.