Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: Laboratoire Aguettant, 1, rue Alexander Fleming, 69007, Lyon, France
Pharmacotherapeutic group: Mineral supplements
ATC code: A12CE02
Selenium is an essential trace element. In human, selenium compounds are glutathione peroxidase and a selenium protein P found in the plasma. In both these proteins, selenium is protein-bound and is present in the form of the amino acid selenocysteine. Other selenium-dependent enzymes are the thioredoxine-reductase and the 5'-deiodinase that catalyses the conversion from tetraiodothyronine (T4) to the active thyroid hormone triiodothyronine (T3).
The selenium-containing glutathionperoxidase is a part of the anti-oxidative protection system of the mammal cell. In case of sufficient quantities of reduced glutathione, the glutathionperoxidase converts a variety of hydroperoxides into relevant alcohols.
The patho-physiological relevance of selenium-dependent reactions has been demonstrated by observations in selenium deficiency. The selenium-containing glutathionperoxidase affects the leucotriene, thromboxane and prostacyclin metabolism. Selenium deficiency inhibits reactions of the immune system, especially the non-specific, cell-bound and humoral reactions. Selenium deficiency affects the activity of a few liver enzymes. Selenium deficiency potentiates oxidatively or chemically induced liver damage and toxicity of heavy metals such as quicksilver and cadmium.
Deficiency of selenium has been associated with an endemic form of cardiomyopathy, Keshan disease. It has also been associated with Kaschin-Beck disease, an endemic osteoarthropathy which causes a severe deformity of the joints.
Clinically manifested selenium deficiency has also been seen to be a result of long-term parenteral nutrition and unbalanced diets. Cardiomyopathies and myopathies are observed most frequently.
In the blood, selenite is mainly absorbed by erythrocytes and enzymatically reduced to hydrogen selenide. Hydrogen selenide serves as the central selenium pool for excretion and for specific incorporation in selenoproteins. In this reduced form, selenium is bound to plasma proteins present in the liver and other organs. The plasmatic secondary transport from the liver to the glutathionperoxidase-synthesing target tissues takes place in the form of selenocystein (selenoprotein P). The further metabolic process of the selenoprotein biosynthesis is currently known only in prokaryotes. Selenocystein is then specifically incorporated into the peptide chains of the glutathionperoxidase.
Excess of hydrogen selenide is transformed into methylated metabolites (methyl selenol, dimethylselenide and trimethylselenonium ion) prior to being excreted into urine and/or exhaled.
The total quantity of selenium in the human body is between 3 mg and 20 mg. In human, selenium is excreted in feces, urine or lung, depending on the administered dosage. Selenium is primarily renally excreted in the form of trimethylselenonium ion. The excretion depends on the selenium status.
The selenium excretion after the intravenous or oral intake takes place in three phases with a terminal half-life of 65 to 116 days.
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 effects in mammals at non-maternally 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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