Selenium plays an important role as an antioxidant, by protecting the body against oxidative damage. Extensive oxidation enhances the production of free radicals, which leads to oxidative stress, and if they are not destroyed, will damage the biological components in the body causing lipid peroxidation, protein carbonylation and DNA strand breakages, ultimately leading to various clinical consequences. Living cells are equipped with a self-defence system to protect from the oxidative stress through the antioxidant mechanisms. There are two types of antioxidants, internal and supplemented antioxidants. Internal antioxidants such as superoxide dismutase (SOD) and glutathione peroxidase (GPx) are enzymes, which are synthesized in the cells and act as primary defence system against free radicals, whereas supplemented antioxidants like vitamins form a secondary defence system against radicals. GPx and other selenium containing enzymes are the major selenium containing internal antioxidants. GPx converts reduced glutathione to oxidized glutathione while reducing peroxides by converting them to harmless alcohols, thus maintaining the membrane integrity. Deficiency of selenium ultimately leads to deficiency of selenium containing internal antioxidants which may cause clinical morbidities.
Selenium is mainly absorbed in the duodenum by enterocytes through amino acid transport systems and catabolised into elemental selenium that gets incorporated into GPx. These selenoproteins are transported into the liver, where they are converted into selenoprotein P (SePP) and distributed to various organs, such as the brain, kidney, heart, spleen, muscles and gonads.
Sources of selenium
Selenium exists predominantly in plants and meat in both inorganic forms such as selenite, selenate, selenide and in organic forms like selenomethionine, methylselenocystine and selenocysteine. Sea food and organ meats are the richest source of selenium. Muscle meat, cereals, grains, egg, vegetables and dairy products are other sources of selenium. Brazil nuts are one of the richest source of selenium. Selenium exists in various chemical forms in different food stuffs as selenate in fish and cabbage, Se-methylselenocysteine in garlic, onions and broccoli, selenomethionine in plant sources and yeast, selenocysteine in animal foods and meats and selenoneine, a recently discovered selenium compound found in chicken, tuna and mackerel. The absorption of selenium compounds varies according to their chemical form; 90% in cases of selenomethionine while that of selenite is 80%.
Selenium in health and disease
Keshan disease is an endemic cardiomyopathy observed in selenium-deficient areas in Keshan County, China. Clinical features of Keshan disease include acute or chronic episodes of a heart disorders characterized by cardiogenic shock and congestive heart failure. The geographical distribution of topsoil selenium in this area is extremely low.
Some studies have suggested that supplementation of selenium could reduce the risks associated with cardiovascular diseases as selenium prevents the oxidative modification of lipids, platelet aggregation and inflammations (1-6). Low levels of plasma selenium are associated with increased risk of cardiovascular disease mortality. Heart disease mortality declined to 55% in men and 68% in women in Finland due to an increase in dietary selenium intake (7).Free radicals produced in the body are highly toxic to the myocardium causing excessive necrosis, and oedema (8). Selenium associated with GPx4 reduces phospholipid hydro peroxides which in turn reduce the accumulation of oxidized LDL in the arterial wall.
Many data are available on the relation between selenium level and acute myocardial infarction (9-11). Derbeneva et al. reported positive changes in patients; the changes being associated with an increased activity, improved overall health and improved cognitive functions in patients with cardiovascular diseases (12). Turan et al. also demonstrated a positive correlation between the selenium level and cardiovascular complications (13).Cominetti et al. found that obese people who consumed Brazil nuts improved both selenium status and lipid profile, especially high-density lipoprotein cholesterol levels, thereby reducing the cardiovascular risks (14). Studies conducted by Schnabel also showed that sodium selenite supplementation increased the antioxidant capacity through GPx-1 activity in endothelial cells and in coronary artery disease patients (15).
Selenium deficiency causes irreversible changes in the neuronal cells and brain injury. Evidence from clinical studies reveal that selenium deficiency leads to cognitive impairment, seizures, Parkinson’s disease and Alzheimer’s disease (16). SePP1 also has an antioxidant role in neuronal cells by preventing the apoptotic cell death due to oxidative damage. A Chinese study revealed the association of low nail selenium concentration and cognitive scores (17). Low selenium levels also deactivates certain centres in the brain leading to Alzheimer’s disease and change in the mood. Studies conducted by Valentine et al. also concluded that interference with SePP1 function damages auditory and motor areas, at least in part by restricting selenium supply to the brain regions (18).
Selenium deficiency leads to various gastrointestinal and thyroid problems. Deficiency of selenium in the diet leads to the lack of absorption of various other trace elements in the duodenum.
Selenium associated with GPx3 protects thyroid cells in the synthesis of T3 and T4 from iodine and thyroglobulin. Sodium selenite or selenomethionine supplementation (80 or200 mg/day) was effective against auto immune thyroid disorders like Hashimoto’s thyroiditis (19).
The fact that immune cells regulating organs such as spleen and liver contain abundance of selenium, reveals the importance of the selenium in immune function/modulation. Data show deficiency of selenium decreases T cell function, and impairs lymphocyte modulations and supplementation of selenium enhances the immunostimulatory effects such as increase in CD3, T cell and cytotoxic cells (20). Roy et al. revealed that supplementation of sodium selenite (200 mg) enhanced the T cell response and Wood et al found an increase in the T cell count using 400 mg of selenium in yeast (21,22). Studies also reported the correlation of plasma selenium levels with the respiratory distress syndrome. Broome et al found that supplementation of sodium selenite (100 mg/day) cleared the poliovirus more rapidly than the placebo (23).
In men, selenium is essential for sperm motility in the form ofGPx4 and SePP1. SePP1, which is synthesized in the liver is transported to the testis, where it is absorbed and enhances the antioxidant potential in the testis. GPx4 found in the mitochondria makeup the midpiece heath of the sperm tail, which protects the sperm by its antioxidant capacity. Later it forms cross links with the proteins in the midpiece and becomes a structural part of the sperm for motility. Scott et al. showed that supplementation with selenomethionine (100mg/day) in men with low initial selenium status and low motility levels, generated improvement in the motility after three months (24). An Italian study revealed that lack of selenium caused infertility, lack of viability and morphological changes and motility in men (25). Clinical trials revealed that 100 mg/day selenium supplementation in subfertile men with low selenium intake significantly increased the sperm motility and paternity.
Studies correlating selenium status and eclampsia in pregnant women demonstrate selenium status was usually decreased due to enhanced plasma volume and this may lead to the pre-eclampsia (26).
Reports suggest organic and inorganic selenium has antimicrobial action. Radhakrishnan et al. conducted the study on antimicrobial activity of propionic and acetic acid derivatives of selenium compounds and found antimicrobial activity against S. aureus, S. typhimurium,E. coli and B. subtilis (27). Others reported that organoselenium compounds were active against S. aureus rather than the E. coli species.
It has been reported that selenium compounds possess anti-ulcer activity through an antioxidant mechanism. Pre-treatment with selenium compounds inhibited inflammatory pathways and enhanced cell growth in the stomach, thereby healing the ulcer. Recently DL-trans-3,4-dihydroxy-1-selenolane (DHS red) a cyclic selenide with GPx like activity has been reported to act as anti-ulcer agent (28).
Studies have found a lower selenium status in diabetic patients compared with controls (29,30). Data suggests the prevalence of diabetes to be greater in men with lower selenium levels. One mechanism may be the antioxidant effect of selenium neutralizing oxidative stress, one of the main causes of diabetes. Another plausible mechanism is the influence of selenium on glucose metabolism. In patients with diabetes, selenium supplementation reduced the expression of NF-kB, which is responsible for the expression of inflammatory proteins such as interleukins and tumour necrosis factor. However, studies conducted by Laclaustra et al. showed that the prevalence of diabetes increased with raised levels of selenium (29). Hence it appears that both low and high selenium intakes could influence the risk of diabetes.
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Keywords :- selenium, cardiovascular disease, nervous system, GI tract, immunity, fertility, pre-eclampsia, antimicrobial, H pylori, diabetes