Source: Health Products Regulatory Authority (IE) Revision Year: 2016 Publisher: biosyn Arzneimittel GmbH, Schorndorfer Str. 32, 70734 Fellbach, Germany
Pharmacotherapeutic group: Mineral supplement
ATC code: A12CE02
Selenium is a co-factor in various enzymes in the human body and therefore belongs to the essential trace elements. To date, more than 25 proteins and protein subunits containing selenium have been identified and most clinical and biochemical effects of selenium can be attributed to their activity. However, not all the effects of selenium are exclusively related to the action of different enzymes.
Selenium-containing glutathione peroxidase and selenium protein P have been identified in humans. Glutathione peroxidase is part of the anti-oxidant protection mechanism of the cell in mammals. As a constituent of glutathione peroxidase, selenium can delay the lipid peroxidation rate and thus the resultant damage to the cell wall. Glutathione peroxidase affects the metabolism of leukotrienes, thromboxanes and prostacyclines. In animals, type I iodothyronine-5'-deiodinase is characterised as a selenium enzyme that converts thyroxine (T4) into triiodothyronine (T3), the active thyroid hormone.
A selenium deficiency is manifested in reduced selenium levels in whole blood or plasma and in the suppression of glutathione peroxidase activity in whole blood, plasma or thrombocytes. The pathophysiological relevance of seleniumdependent reactions has been demonstrated in studies of selenium deficiencies in humans and animals: Selenium deficiency activates and inhibits the response of immunological mechanisms, particularly non-specific cell and body fluid responses. Selenium deficiency affects the activity of various hepatic enzymes. Selenium deficiency potentiates damage occasioned to the liver by oxidative or chemical factors and the toxicity of heavy metals such as mercury and cadmium.
For humans, the following diseases are described as a consequence of selenium deficiency: Keshan disease, an endemic cardiopathy, and Kaschin-Beck disease, an endemic osteoarthropathy that is associated with very severe deformity of the joints. Clinically manifest selenium deficiency is also observed as a consequence of long-term parenteral nutrition and unbalanced diets.
Sodium selenite is not immediately converted to proteins. In the blood, the majority of the supply of selenium is used by the erythrocytes and converted to hydrogen selenide under the action of enzymes. Hydrogen selenide acts as a central pool of selenium for both elimination and the specific integration of selenium in selenoproteins. Reduced selenium binds to plasma proteins that migrate to the liver and other organs. Secondary plasma transport from the liver to the target tissues, that produce glutathione peroxidase by synthesis, probably occurs via a P-selenoprotein containing selenocysteine. The subsequent metabolic pathway of selenoprotein synthesis has to date only been studied in prokaryotes. In the metabolic process, selenocysteine is specifically incorporated in the peptide chains of glutathione peroxidase.
All excess hydrogen selenide is metabolised via methylselenol and dimethylselenide to the trimethylselenonium ion, the principal elimination product.
After oral administration, selenium is principally absorbed from the small intestine. Absorption of sodium selenite in the intestine is not regulated by homeostatic mechanisms. Depending on the concentration of sodium selenite and the presence of related substances, it is usually between 44% and 89%, and sometimes more than 90%. The amino acid cysteine increases the absorption of sodium selenite.
The total quantity of selenium present in the human body is between 4 mg and 20 mg. Humans excrete selenium in the faeces, via the kidneys and through the respiratory system, depending on the amount administered. Selenium is predominantly eliminated in the form of the trimethylselenonium ion via the kidneys. Elimination is dependent on the selenium status.
After intravenous or oral administration, the process of selenium elimination was divided into three phases. After oral administration of 10 micrograms in the form of [75Se] sodium selenite, 14–20% of the absorbed selenium is eliminated via the kidneys in the first two weeks, while almost nothing was eliminated via the lungs and skin. The retention of selenium in the whole body decreased in three phases, with half-lives of 0.7–1.2 days in phase 1, 7–11 days in phase 2 and 96–144 days in phase three. The selenium concentration decreased more rapidly in the liver, heart and plasma than in the skeletal muscles or in the bones. Of an intravenously administered dose of [75Se] sodium selenite, 12% was excreted in the first 24 hours. A further 40% was eliminated with a biological half-life of 20 days. The half-life of the third phase was 115 days.
Elimination after oral and intravenous administration of a physiological dose of [74Se] sodium selenite was compared directly: after administration of 82 micrograms selenium in the form of sodium selenite, 18% of the intravenous dose and 12% of the oral dose was eliminated via the kidneys in the first 24 hours together with metabolised physiological selenium. After this phase, the process of elimination by both routes of administration is more or less the same. In healthy volunteers, the elimination of orally and parenterally administered sodium selenite was comparable.
Published literature on single and repeated dose toxicity of selenium and sodium selenite reveals no evidence for adverse health effects in addition to those already known from experience in humans. Toxicity to reproduction was only found at very high doses and no evidence was found for a risk of teratogenic ef-fects in mammals at nonmaternally toxic doses. Although mutagenicity and carcinogenicity data are inconclusive, because there is evidence for both positive as well as negative effects, the adverse effects on these endpoints are generally found at concentrations above the normal physiological levels.
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