Thesis Abstract

Abstract
Selenium is a trace element that is essential for human health, playing a critical role in various physiological processes such as antioxidant defense, thyroid hormone metabolism, and immune function. Both selenium deficiency and toxicity can have significant effects on human health. Selenium deficiency is associated with conditions such as Keshan disease, Kashin-Beck disease, and myxedematous endemic cretinism, which can manifest as cardiomyopathy, osteoarthritis, and cognitive impairment, respectively. In contrast, selenium toxicity can result in selenosis, a condition characterized by hair and nail loss, skin lesions, gastrointestinal disturbances, and neurological abnormalities. The effects of selenium toxicity and deficiency on humans are complex and multifaceted. Selenium deficiency can impair the body's antioxidant defense mechanisms, leading to increased susceptibility to oxidative stress and potentially contributing to the development of chronic diseases such as cancer, cardiovascular disease, and neurodegenerative disorders. Additionally, selenium deficiency has been linked to compromised immune function, thyroid dysfunction, and male infertility. On the other hand, selenium toxicity can occur when the intake of selenium surpasses the body's capacity to metabolize and excrete it. Chronic exposure to high levels of selenium can lead to the accumulation of selenium in tissues, resulting in oxidative damage and disruption of cellular functions. Selenium toxicity has been associated with adverse effects on the skin, hair, nails, nervous system, and gastrointestinal tract. Furthermore, excessive selenium intake has been implicated in the development of diabetes, cardiovascular disease, and other health conditions. The impact of selenium toxicity and deficiency on human health underscores the importance of maintaining optimal selenium status through a balanced diet and, if necessary, supplementation. Strategies to prevent selenium deficiency include consuming selenium-rich foods such as Brazil nuts, seafood, eggs, and organ meats. However, care must be taken to avoid excessive selenium intake, as the tolerable upper intake level for selenium has been established to prevent toxicity. In conclusion, selenium is a vital micronutrient with diverse roles in human physiology, and both deficiency and toxicity can have profound effects on health. Understanding the mechanisms underlying the effects of selenium imbalance is crucial for developing strategies to optimize selenium status and mitigate the risks associated with inadequate or excessive selenium intake.

Thesis Overview

INTRODUCTION

1.1.          BACKGROUND INFORMATION

Selenium (Se) is an essential trace element having biological functions of utmost importance for human health. Different from the other (semi) metals, it is incorporated into proteins by a co-translational mechanism as part of the amino acid selenocysteine (SeCys), the 21st amino acid used for protein synthesis in humans, whereas only a few of them have been functionally characterized. Most Se-proteins participate in antioxidant defence and redox state regulation, particularly the families of more specific essential roles, such as iodothyronine deiodinases (DIOs) which are involved in thyroid hormones metabolism, GPx4 which is essential for spermatogenesis, and selenophospathe synthetases 2 (SPS2) participating in Se-protein biosynthesis.

Other Se-proteins may be involved in important biological processes, but their exact mechanism of action is still yet to be fully understood. Despite the scarce knowledge of the precise biochemical functions, a very large number of studies have been carried out in the last two decades showing that insufficient Se levels, and particularly Se-proteins, are associated with several human diseases including cancer, diabetes, cardiovascular and immune system disorders. In most cases, the link lies in the contrast to the oxidative stress that may be booth causing or caused by the disease. In this context, it is important to decipher whether and adequate Se status may contrast the risk factors for health disorders, or Se supplementation may improve the therapy when Se metabolism is altered.

Despite many studies that have suggested a beneficial effect from Se supplementation to general health protection, most of them have remarked that it is limited to general health protection, most of them have remarked that it is limited to the initially inadequate Se status. Conversely, care should be taken when using supplements because excessive Se intake leads to toxic effects, and recent studies have shown that even sub-toxic doses may be negatively impacting, for example by increasing the risk of type 2 diabetes.