Selenium and selenoproteins: from endothelial cytoprotection to clinical outcomes.

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.

The role of selenoproteins in cancer.

Evidence has shown that metabolic disorders are common in tumor cells, leading to increased oxidative stress. The increase in the production of reactive oxygen species (ROS) associated with low antioxidant activity has been related to several types of cancer. Selenium, an antioxidant micronutrient, may function as an antimutagenic agent, preventing the malignant transformation of normal cells. A review of the literature was conducted based on a survey of articles published between 2000 and 2009 in the PubMed database; 39 articles that analyzed the relationship between cancer, oxidative stress and selenium supplementation were selected. The protective effect of this mineral is especially associated with its presence in the glutathione peroxidase and thioredoxin reductase, enzymes that are known to protect DNA and other cellular components against oxidative damage caused by ROS. Several studies have shown reduced expression of these enzymes in various types of cancer, especially when associated with low intake of selenium, which may increase the damage. Selenium supplementation appears to reduce the risk of some types of cancer by reducing oxidative stress and DNA damage. However, further studies are needed to clarify the adequate dose of selenium for each situation (sex, geographic location, and type of cancer).

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).