Thesis Abstract

Abstract
Selenium is a trace element that is essential for human health, playing a crucial role in various physiological processes. Both selenium toxicity and deficiency can have significant impacts on human health. This research project aims to investigate the effects of selenium toxicity and deficiency on humans. Selenium toxicity can occur when there is an excessive intake of selenium, either through diet, supplements, or environmental exposure. Chronic selenium toxicity can lead to selenosis, a condition characterized by symptoms such as hair and nail loss, garlic breath odor, gastrointestinal disturbances, and neurological abnormalities. Acute selenium toxicity can result in more severe symptoms, including respiratory distress, heart failure, and even death. It is important to understand the sources of selenium exposure and factors that contribute to toxicity to prevent adverse health effects. On the other hand, selenium deficiency is a widespread issue globally, particularly in regions where the soil selenium content is low. Selenium deficiency can result in various health problems, including an increased risk of cardiovascular diseases, compromised immune function, and thyroid disorders. In pregnant women, selenium deficiency can lead to complications such as preeclampsia and miscarriage. Understanding the consequences of selenium deficiency is crucial for developing strategies to address this nutritional deficiency and improve public health outcomes. This research project will explore the mechanisms through which selenium toxicity and deficiency affect human health at the molecular and cellular levels. It will investigate how selenium interacts with various biological pathways and enzymes, impacting processes such as antioxidant defense, thyroid hormone metabolism, and immune response. By elucidating these mechanisms, this research aims to provide insights into the pathophysiology of selenium-related disorders and identify potential therapeutic targets for intervention. Furthermore, this project will examine the diagnostic methods available for assessing selenium status in individuals, including blood tests and hair analysis. Understanding how to accurately measure selenium levels in the body is essential for identifying individuals at risk of toxicity or deficiency and guiding appropriate interventions. Overall, this research project will contribute to a better understanding of the effects of selenium toxicity and deficiency on human health, with the ultimate goal of improving public health strategies and promoting optimal selenium nutrition for overall well-being.

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.