Đăng xuất
Pharmacotherapeutic group: Mineral supplement. ATC code: A12CE02.
Pharmacology: Pharmacodynamics: Selenium is an essential trace element. To date, 20 selenoproteins have been identified in rodents. Glutathione peroxidase and a selenium-binding protein called selenoprotein P found in plasma have been detected or purified in humans. In both proteins, selenium is protein-bound in the form of the amino acid selenocysteine. In animals, 5'- deiodinase was recently characterized as a selenium enzyme, which catalyzes the conversion of tetraiodothyronine (T4) to the active thyroid hormone triiodothyronine (T3).
The selenium-containing glutathione peroxidase is part of the antioxidant protection system of the mammalian cell. In the presence of sufficient amounts of substrate, i.e. H. reduced glutathione, glutathione peroxidase converts a variety of different hydroperoxides into corresponding alcohols. In cellular or subcellular model systems it has been shown that the integrity of cellular and subcellular membranes crucially depend on the integrity of the glutathione peroxidase system. Synergistic action with vitamin E in various cell fractions is postulated but has not been conclusively proven.
Selenium as a component of glutathione peroxidase can reduce the rate of lipid peroxidation and the resulting membrane damage. Not all of the effects of selenium can be explained solely by the activity of glutathione peroxidase.
The pathophysiological relevance of the selenium-dependent reactions has been proven by observations of selenium deficiency in humans and animals: the selenium-containing glutathione peroxidase influences leukotriene, thromboxane, and prostacyclin metabolism.
Selenium deficiency activates and inhibits immune defense reactions, especially the non-specific, cell-bound and humoral reactions. Selenium deficiency affects the activity of some liver enzymes. Selenium deficiency potentiates oxidative or chemically induced liver damage as well as the toxicity of heavy metals such as mercury and cadmium.
Deficiency symptoms in humans: Keshan disease, an endemic cardiomyopathy, and the so-called Kaschin-Beck disease, an also endemic osteoarthropathy with severe deformation of the joints, have been described as selenium deficiency diseases. Clinically manifest selenium deficiency has also been observed as a result of long-term parenteral nutrition and balanced diets.
Cardiomyopathies and myopathies of the skeletal muscles in particular occurred.
Epidemiological studies indicate an inverse correlation between blood selenium levels and the incidence of cardiovascular diseases (cardiomyopathies, arteriosclerosis, myocardial infarction) as well as tumor diseases (especially of the digestive tract, breast and liver). Decreased plasma selenium levels may occur in patients with renal insufficiency and in gastrointestinal diseases. Suboptimal selenium intake leads to reduced glutathione peroxidase activity in humans and animals, but does not lead to any clinically tangible symptoms.
Selenium deficiency can be detected by reduced whole blood or plasma selenium levels and by reduced glutathione peroxidase activities in whole blood, plasma or platelets.
Pharmacokinetics: Sodium selenite is not incorporated directly into proteins. In the blood, selenite is mainly absorbed by erythrocytes and enzymatically reduced to hydrogen selenide. Hydrogen selenium serves as a central selenium pool for excretion and for targeted incorporation into selenoproteins. In this reduced form, selenium is bound to plasma proteins that travel to the liver and other organs.
The secondary plasmatic transport from the liver into the target tissue that synthesizes glutathione peroxidase probably occurs in the form of the P-Selenoprotein containing selenocysteine. The further metabolic course of selenoprotein biosynthesis is currently only known in prokaryotes. Selenocysteine is then specifically incorporated into the peptide chains of glutathione peroxidase during translation.
Excess hydrogen selenium is metabolized via methylselenol and dimethylselenide to trimethy|selenonium ion, the main excretion product.
After oral administration, selenite is primarily absorbed from the small intestine. Intestinal absorption of sodium selenite is not homeostatically regulated. Depending on the concentration and accompanying substances, it is between 44% and 89%, occasionally over 90%. The amino acid cysteine promotes the sodium selenite absorption.
The total amount of selenium in the human body is between 4 mg and 20 mg. Depending on the dose administered, selenium is excreted in humans via the faeces, urine or lungs. Selenium is primarily excreted renally in the form of the trimethylselenonium ion. Excretion depends on selenium status.
Selenium excretion after intravenous or oral administration occurs in three phases. When 10 mcg was administered orally in the form of [75Se] sodium selenite, 14-20% of the absorbed dose of selenium was excreted in the urine in the first two weeks, while practically no excretion via the lungs or skin was detected. Total body retention of selenium decreased triphasically with a half-life of 0.7-1.2 days in the 1st phase, 7-11 days in the 2nd phase and 96-144 days in the 3rd phase. Selenium concentrations decreased more rapidly in liver, heart, and plasma than in skeletal muscle or bone. Of an intravenously administered dose of [75Se] sodium selenite, 12% was excreted within the first 24 hours. An additional 40% was eliminated with a biological half-life of 20 days. The half-life of the third phase was determined to be 115 days.
In a direct comparison between oral and intravenous administration of a physiological dose of [74Se] sodium selenite, after intravenous administration of 82 mcg selenium in the form of sodium selenite, 18% of the dose was absorbed in the first 24 hours, and after peroral administration 12% of the absorbed Dose excreted in the urine together with metabolically exchanged body selenium. The excretion then proceeds in the same way for both types of application. Sodium selenite administered orally and parenterally is comparable in healthy subjects.
