INTRODUCTION:

Selenium (Se) is an essential trace element in the human body¹, an important part of the antioxidant enzymes that protect cells against the effects of free radicals that are produced during the normal oxygen metabolism. The body has developed defenses, such as antioxidants, to control the levels of free radicals, which can damage cells and contribute to the development of some chronic diseases^2-6. The Se content of plants varies tremendously according to its concentration in soil. A region in which the Se concentration in the soil is very low like Australia, northeast China, northern North Korea, south central China, Nepal, and Central Africa⁷.People living in Se-poor areas have very low Se intake. For example, the Nepalese have a Se intake of 23 mg/day⁸; Selenium accumulating or volatilizing plants may be used for phytoremediation of selenium pollution and as fortified foods. Several transgenic approaches have been used successfully to further enhance plant selenium accumulation, tolerance, and volatilization, upregulation of genes involved in sulphur/selenium assimilation and volatilization, methylation of selenocysteine, and conversion of selenocysteine to elemental Se.

Lab and field trials with different transgenic plants have yielded promising results, showing up to nine fold higher levels of selenium accumulation and up to threefold faster⁹.

Sources:

Dietary selenium comes from nuts, cereals, meat, fish, and eggs. Brazil nuts are the richest ordinary dietary source [Table 1]^10,11

Minerals containing selenium are very uncommon. Rarely, ores that contain high concentrations of selenium have been discovered. Most selenium is recovered as a by-product of processing copper ores¹². Selenium levels in soils and waters increase, because selenium settles from air and selenium from waste also tends to end up in the soils of disposal sites. The oxygen levels in the soil and the acidity of the soil will increase mobile forms of selenium. Higher oxygen levels and increased acidity of soils is usually cause by human activities, such as industrial and agricultural processes.

Table 1: Dietary Source of Selenium

Food	Micrograms (μg)	Percent DV*
Brazil nuts, dried, unblanched, 1 ounce	544	780
Tuna, light, canned in oil, drained, 3 ounces	63	95
Beef, cooked, 3½ ounces	35	50
Spaghetti w/ meat sauce, frozen entrée, 1 serving	34	50
Cod, cooked, 3 ounces	32	45
Turkey, light meat, roasted, 3½ ounces	32	45
Beef chuck roast, lean only, roasted, 3 ounces	23	35
Chicken Breast, meat only, roasted, 3½ ounces	20	30
Noodles, enriched, boiled, 1/2 cup	17	25
Macaroni, elbow, enriched, boiled, 1/2 cup	15	20
Egg, whole, 1 medium	14	20
Cottage cheese, low fat 2%, 1/2 cup	12	15
Oatmeal, instant, fortified, cooked, 1 cup	12	15
Rice, white, enriched, long grain, cooked, 1/2 cup	12	15
Rice, brown, long-grained, cooked, 1/2 cup	10	15
Bread, whole wheat, commercially prepared, 1 slice	10	15
Walnuts, black, dried, 1 ounce	5	8
Bread, white, commercially prepared, 1 slice	4	6
Cheddar cheese, 1 ounce	4	6

Substitutes and Alternative Sources:

For instance, high purity silicon is now being used in the production of rectifiers. Cerium oxide is being used in glass production in place of selenium. Coal deposits contain 1.5 parts per million selenium. This is 80 times the amount of selenium found in copper deposits. Unfortunately, a method of removing this selenium from coal has not been developed.

Chemical forms of selenium:

Selenoproteins:

Selenocysteine (Sec) has a similar structure to cysteine, with an atom of Se taking the place of sulfur. Proteins that include a selenocysteine are called selenoproteins. The general pathway of selenoprotein synthesis involves four cell genes, selA, selB, selC, and selD. There are four steps in this mechanism. The first step involves tRNA (selC), which gets charged with serine. SelA then converts this serine to selenocysteine in step two. Afterwards, selD provides a Se donor, and the selB translation factor recognizes the selenocysteyl-tRNA and then delivers it to the UGA on the ribosome^13,14.

Glutathione peroxidases (GPx):

In this group, selenocysteine is located in the N-terminal portion of a relatively short function domain¹⁵. The major physiological role of GPx is to maintain appropriately low levels of hydrogen peroxides within the cell, thus decreasing potential damage from free radicals. It provides a second line of defense against hydrogen peroxides, which can damage membranes and other cell structures¹⁶. GPx1 is an antioxidant in the cell cytosol and thought to be one of the major antioxidant proteins in mammals. GPx2 and GPx3 are antioxidants found in the gastrointestinal tract and plasma. GPx4 is also referred to as a phospholipids hydroperoxide glutathione peroxidase (PHGPx), since it specially reduces fatty acid hydroperoxides to phospholipids¹⁷. GPx5 and GPx6 are readily detected in the mouse epidermis and olfactory epithelium, respectively^18,19.

Selenoprotein P:

Selenoprotein P (Se-P) is the major plasma selenoprotein. Se-P binds to cells and appears to be expressed in various tissues, such as arterial endothelial cells and hepatic sinusoidal endothelial cells. Se-P acts as a Setransport protein and an antioxidant on the endothelium²⁰.

Selenoproteins W and R:

Se-W is a low-molecular mass selenoprotein (87 amino acid protein) containing one selenocysteine residue; it exists in four forms. One isoform has glutathione (GSH) bound to a speci.c cysteine residue, which indicates that Se-W may have redox functions. Se-R contains selenocysteine in the C-terminal portion²¹, and the function of this selenoprotein is still unknown.

Thioredoxin reductase:

Thioredoxin reductase (Trx) is a widely distributed redox protein that regulates several intracellular redoxdependent processes and stimulates the proliferation of both normal and tumor cells. This group is characterized by the presence of selenocysteine in the C-terminal sequences¹⁵. Trx is a hydrogen donor for ribonucleotide reductase. It also regulates enzymes and transcription factors by thiol redox control and is one of the proteins involved in the repair mechanisms essential for DNA synthesis.

Structure:

Electron Dot Model:

Atomic Structure of Selenium:

Figure 1: Atomic Structure of Selenium

Table 2: Properties of Selenium:

General properties
Name, symbol, number	Selenium, Se, 34
Element category	Non-metal
Group, period, block	16, 4, p
Standard atomic weight	78.96 g.mol^-1
Electron configuration	4s² 3d¹⁰ 4p⁴
Electrons per shell	2, 8, 18, 6
Physical properties
Phase	Solid
Density (near r.t.)	(gray) 4.81 g·cm⁻³
Density (near r.t.)	(alpha) 4.39 g·cm⁻³
Density (near r.t.)	(vitreous) 4.28 g·cm⁻³
Liquid density at m.p.	3.99 g·cm⁻³
Melting point	494 K / 221°C / 430°F
Boiling point	958 K / 685°C / 1265°F
Critical point	1766 K, 27.2 MPa
Heat of fusion	(gray) 6.69 kJ·mol⁻¹
Heat of vaporization	95.48 kJ·mol⁻¹
Specific heat capacity	(25°C) 25.363 J·mol⁻¹·K⁻¹
Atomic properties
Electronegativity	2.55 (Pauling scale)
Ionization energies	1st: 941.0 kJ·mol⁻¹ 2nd: 2045 kJ·mol⁻¹ 3rd: 2973.7 kJ·mol⁻¹
Atomic radius	120 pm
Covalent radius	120±4 pm
Vander Waals radius	190 pm
Chemical properties
Crystal structure	Hexagonal
Magnetic ordering	diamagnetic
Thermal conductivity	(300 K) (amorphous) 0.519 W·m⁻¹·K⁻¹
Thermal expansion	(25°C) (amorphous) 37 µm·m⁻¹·K⁻¹
Speed of sound (thin rod)	(20 °C) 3350 m/s
Young's modulus	10 GPa
Shear modulus	3.7 GPa
Mohs hardness	2.0
Brinell hardness	736 MPa

Pharmacokinetics:

Absorption and bioavailability:

Several forms of selenium enter the body as part of amino acids within proteins. The two most common forms of the element that enter the body are selenomethionine and selenocysteine which are found mainly in plants and animals respectively²². The primary sites of absorption are from throughout the duodenum. Virtually no absorption occurs in the stomach and very little takes places in the remaining two segments of the small intestine²³. Selenomethionine is absorbed from the duodenum at a rate close to 100%. Other forms of the element have been shown to also be generally well absorbed. However, absorption of inorganic forms of the element varies widely due to luminal factors²². This variation in absorption reduces total absorption of all forms to somewhere between 50 and 100%. Selenium absorption is not affected by body selenium status. Absorption of selenium is closely related to multiple nutritional factors that inhibit or promote absorption. Vitamins A, C and E along with reduced glutathione enhance absorption of the element. In contrast, heavy metals (i.e. mercury) decrease absorption via precipitation and chelation²³.

Distribution:

The exact mechanisms of selenium transport are thus far unclear and debatable. Selenium has been hypothesized to enter red blood cells via diffusion and carried throughout the body. Within the blood, free selenium binds to lipoproteins such as VLDL or LDL. The transport properties of a second protein, identified as selenoprotein P, have been met with opposing viewpoints. The protein is found in the plasma and is believed to be a carrier by some²³. The presence of selenocysteine within the structure inhibits the transport abilities of the protein²². In the form of selenomethionine, selenium appears to be biologically inactive and not subject to selenium homeostatic regulation. Catabolism releases the element to enter the selenium pool, where it can be incorporated into selenoproteins such as glutathione peroxidase²⁴ or be excreted. Ingested selenocysteine is not incorporated directly into proteins but is catabolized, releasing its selenium for utilization. Inorganic forms of selenium enter the selenium pool only. Expansion of the central selenium pool beyond the requirements for selenoprotein synthesis results in excretion of the element. Ingestion of selenium as selenomethionine will result in higher tissue selenium levels than ingestion of the same amount of selenium as Selenocysteine or as inorganic selenium. Selenium selectively deposits in the liver (15%), kidneys (5%), spleen (1%) and pancreas (0.5%). The remainder is deposited uniformly throughout all other organs and tissues. Of the selenium deposited in any organ or tissue, 10% is retained with a biological half-life of 3 days, 40% is retained with a biological half-life of 30 days, and 50% is retained with a biological half-life of 150 days²⁵.

Metabolism:

Se exists in mostly organic forms in normal diets. Organic Se is present in foods mainly in the form of selenomethionine, selenocysteine and Semethylselenocysteine, whereas inorganic Se either as selenite or selenate occurs much less frequently and in very low amounts. Of the organic forms, selenomethionine is the predominant form in most Se rich diets. Both organic and inorganic forms of Se appear to be utilized with similar efficacy in the body to produce selenoproteins²⁶, but the Se enters at different points in metabolism depending on chemical form. A metabolic scheme showing Se metabolism is presented in [Figure 3]. Inorganic forms of Se, selenite and selenate are reduced (from the valence +4 and +6, respectively) by glutathione (GSH). A number of intermediate metabolic steps lead to the generation of H2Se, or they directly enter the metabolic pool ^[26,27]. SSe produces H2Se and/or elemental Se (Se0) viaselenodiglutathione (GSSeSG) through reduction by thiols and NADPH^-dependent reductases ^[28,29]. This reduction pathway is tightly connected to the production of the superoxide (O₂•⁻) radical.⁺, the anticarcinogenic action as well as toxicity of Se compounds is due to the catalytic nature of the selenide anion (RSe^-), the subsequent generation of O₂•^- and oxidative stress, which induces apoptosis and may contribute to carcinostatic activity.

Figure 2: Distribution of Selenium⁶⁵

Figure 3: Schematic representation of the Se metabolic pathway^{35, 36}

Figure 4: Selenite reduction pathway and generation of superoxide³⁰

Excretion:

Selenium homeostasis is regulated primarily through excretion. Selenium is excreted via two main paths: urinary (50-67%) and faecal (40-50%)²³. Extremely high intakes of selenium can lead to ventilatory elimination of the mineral in the form of dimethylselenide. Excretion via the lungs is characterized by a garlic smell odor to the volatile selenium compound ^[22,23]. Urinary excretion is the primary route of regulation under normal physiological conditions.

Mechanism of action:

Functionally, there appear to be at least two distinct families of selenium containing enzymes. The first includes the glutathione peroxidases and thioredoxin reductase, which are involved in controlling tissue concentrations of highly reactive oxygen-containing metabolites.

The first direct evidence of free radical generation by Se compounds was published in 1989 by³¹ who showed that the oxidation of GSH by SSe leads to the production a free radical O₂•⁻, and elemental SeO with the intermediate formation of GSSeSG. AlthoughO₂•⁻ has relatively low reactivity and toxicity, it gives rise to secondary oxidative products. The dismutation of O₂•⁻ yields H₂O₂, which on its own is not toxic, but its high reactivity is realized in vivo through Fenton-like reactions, where H₂O₂ reacts with partially reduced metal ions such as Fe2⁺ or Cu⁺ to form •OH. In contrast to H₂O₂, •OH can directly inflict DNA damage and it is considered the most important radical in ROS-related DNA damage^32,
33. There is a great deal of chemical and biological evidence that Se is a prooxidant catalyst³⁰. The anticarcinogenic action of Se compounds is due to the catalytic nature of the selenide anion (RSe^-), the subsequent generation of O2•^- and oxidative stress, which induces apoptosis and may contribute to carcinostatic activity^34,35. During stress, infection, or tissue injury, selenoenzymes may protect against the damaging effects of hydrogen peroxide or oxygen-rich free radicals. The biochemical function of glutathione peroxidase is to reduce lipid hydroperoxides to their corresponding alcohols and to reduce free hydrogen peroxide to water.

Figure 5: Glutathione peroxidase (GSH-Px) catalyzes certain reactions that remove reactive oxygen species such as peroxide³⁶

Therapeutic Uses:

Antioxidant

Selenium is a component of glutathione peroxidase, which possesses antioxidant activity and demonstrates antioxidant properties in humans. Long-term clinical benefits remain controversial^37-50.

Keshan disease

Keshan disease is a cardiomyopathy (heart disease) restricted to areas of China in people having an extremely low selenium status. Prophylactic administration of sodium selenite has been shown to significantly decrease the incidence of this disorder. Organic forms of selenium (such as selenized yeast or Se-yeast) may have better bioavailability than selenite and thus may be better preventative treatments for Keshan disease. Selenium is used to treat and prevent selenium deficiency (for example in those with HIV or receiving enteral feedings) ^37-50.

Bronchitis

Because selenium is proposed to have a role in immune function, selenium supplementation has been studied in patients with various infections. Some evidence suggests that selenium may promote recovery from bronchitis and pneumonia caused by respiratory syncytial virus (RSV) ^37-50.

Heart disease:

Lower antioxidant intake there is a greater incidence of heart disease⁵¹. Evidence also suggests that oxidative stress from free radicals, which are natural by-products of oxygen metabolism, may promote heart disease^52-5⁴. For example, it is the oxidized form of low-density lipoproteins (LDL, often called "bad" cholesterol) that promotes plaque build-up in coronary arteries⁶¹. Selenium is one of a group of antioxidants that may help limit the oxidation of LDL cholesterol and thereby help to prevent coronary artery disease^52-54.

Cancer treatment

Several studies suggest that low levels of selenium (measured in the blood or in tissues such as toenail clippings) may be a risk factor for developing cancer, particularly prostate, gastrointestinal, gynecological, and colorectal cancer. Selenium affects cancer risk in two ways. As an anti-oxidant, selenium can help protect the body from damaging effects of free radicals. Selenium may also prevent or slow tumor growth. Certain breakdown products of selenium are believed to prevent tumor growth by enhancing immune cell activity and suppressing development of blood vessels to the tumor⁵⁵.

HIV/AIDS

HIV/AIDS malabsorption can deplete levels of many nutrients, including selenium. Selenium deficiency is associated with decreased immune cell counts, increased disease progression, and high risk of death in the HIV/AIDS population^56,57.HIV/AIDS gradually destroys the immune system, and oxidative stress may contribute to further damage of immune cells. Antioxidant nutrients such as selenium help protect cells from oxidative stress, thus potentially slowing progression of the disease⁵⁸.Selenium also may be needed for the replication of the HIV virus, which could further deplete levels of selenium⁵⁹.

Skin disorders

Taking selenium by mouth has been studied for its effects on psoriasis and lesions induced by arsenic or the human papilloma virus (HPV). Selenium has also been used to treat eczema and to increase the rate of burn wound healing. Although some results appear promising, the overall results are mixed^37-50.

Arthritis (osteoarthritis, rheumatoid arthritis)

Selenium-ACE, a formulation containing selenium with three vitamins, has been promoted for the treatment of arthritis. The body's immune system naturally makes free radicals that can help destroy invading organisms and damaged tissue, but that can also harm healthy tissue⁶⁰. Selenium, as an antioxidant, may help to relieve symptoms of arthritis by controlling levels of free radicals.

Dose:

Dietary Requirements: The below doses are based on scientific research, publications, traditional use, or expert opinion.

Table 3: Recommended Dietary Allowances (RDA) for Selenium for Infants, Children and Adults⁶¹

Selenium Requirements Daily Reference Intakes
Life stage	Selenium (mcg/day)
Infants
0 – 6 months	15
7 – 12 months	20
Children
1 – 3 years	20
4 – 8 years	30
Males
9 – 13 years	40
14 – 18 years	55
19 – 30 years	55
31 – 50 years	55
51 – 70 years	55
>70 years	55
Females
9 – 13 years	40
14 – 18 years	55
19 – 30 years	55
31 – 50 years	55
51 – 70 years	55
>70 years	55
Pregnancy
<18 years	60
19 – 30 years	60
31 – 50 years	60
Lactation
<18 years	70
19 – 30 years	70
31 – 50 years	70

Deficiency

Selenium deficiency is relatively rare in healthy, well-nourished individuals. It can occur in patients with severely compromised intestinal function, those undergoing total parenteral nutrition, and also⁶² on advanced-aged people (over 90). Also, people dependent on food grown from selenium-deficient soil are also at risk. However, although New Zealand has low levels of selenium in its soil, adverse health effects have not been detected⁶³.

Selenium deficiency may only occur when a low selenium status is linked with an additional stress such as chemical exposure or increased oxidant stress due to vitamin E deficiency⁶⁴.

Adverse Drug Reactions:

Toxicity

Selenium toxicity may cause gastrointestinal symptoms (nausea, vomiting, abdominal pain, diarrhea, garlic-like breath odor, and metallic taste), neuromuscular-psychiatric disturbances (weakness/fatigue, lightheadedness, irritability, hyperreflexia, muscle tenderness, tremor, and peripheral neuropathy), dermatologic changes (skin rash/dermatitis/flushing, fingernail loss /thickening/ blotching/streaking/paronychia, and hair changes/loss), liver dysfunction, kidney dysfunction, thrombocytopenia (low blood platelets), immune alterations (natural killer cell impairment), thyroid dysfunction (decreased T3), reduced sperm motility, or growth retardation. Acute selenium poisoning may cause fever, gastrointestinal symptoms (nausea, vomiting, pain, anorexia), liver or kidney functional impairment, respiratory distress, cardiac complications (EKG changes, increased creatine kinase levels, heart damage), and even death if levels are high enough. Other symptoms similar to chronic selenium toxicity may also occur. Chronic low selenium levels are associated with the development of cardiomyopathy and possibly with coronary artery disease ^37-50.

Interactions:

Nutrient interactions

Selenium probably interacts with those nutrients which affect the pro-oxidant/antioxidant balance of the cell. Selenium, in combination with vitamin E, causes many metabolic functions to operate. Selenoprotein glutathione peroxidase appears to support the activity of vitamin E in limiting the oxidation of lipids. Selenium also enhances the anti-oxidant effect of vitamin E. Selenoprotein thioredoxin reductase can maintains the antioxidant function of vitamin C by catalyzing its regeneration.

Interactions with Drugs

Agents that alter the pH of the stomach may decrease the absorption of selenium. Concern has been raised that antioxidants may interfere with radiation therapy or some chemotherapy agents (such as alkylating agents, anthracyclines, cisplatin, doxorubicin or platinums), which themselves can depend on oxidative damage to tumor cells for anti-tumor effects. Patients considering the use of selenium during chemotherapy or radiation therapy should discuss this choice with their medical and radiation oncologists. High-dose steroid therapy may decrease plasma selenium levels. Selenium has been suggested to increase the effects of erythropoietin in hemodialysis patients. Chronic high selenium levels may decrease sperm motility, although effects on fertility are not known^37-50.

Interactions with Herbs and Dietary Supplements

Selenium is a component of glutathione peroxidase, which possesses antioxidant activity and demonstrates antioxidant properties in humans. Long-term clinical benefits remain controversial. Selenium may add to the effects of other antioxidants in the body, such as vitamins A, C, and E, lycopene, green tea, soy, grape seed extract, or melatonin. The antioxidant activity of selenium may be affected by n-3 polyunsaturated fatty acids (n-3 PUFA). cisplatin, doxorubicin. Vitamin C appears to increase the absorption of natural selenium (found in foods) but not sodium selenate (found in supplements). Selenium supplementation may affect the absorption of calcium and magnesium.

Topical preparations containing selenium may interact with the metals in costume jewelry. Patients should remove all their jewelry before applying the shampoo or lotion. With regard to dietary supplements, there is some evidence that vitamin C inactivates selenium within the digestive tract^37-50.

CONCLUSIONS:

Selenium which is free radical scavenger, as free radicals causes damage to cell and lead to degenerative disease like HIV/AIDS, cardiovascular disease, hypothyroidism, osteoarthritis, rheumatoid arthritis (RA), stroke, atherosclerosis, colorectal cancer, esophageal cancer, prostate cancer, gastric cancer, lung cancer, skin cancer. So Selenium is mineral antioxidant which is used to treat such disease. No other trace element holds as much promise as a preventive agent against one of the most dreaded diseases of mankind, cancer, as does Se. Promising cancer chemoprevention activities have been observed with the synthetic organoselenium derivatives. The promise is counterbalanced by a lack of knowledge regarding the safe levels of Se that would be maximally effective. Selenium acts as a co-factor for enzyme glutathione peroxidase, which aids in the regeneration of glutathione. It is also a major antioxidant nutrient that protects cell membranes and prevents free radical generation, thereby decreasing the risk of cancer and disease of the heart and blood vessels. Areas of selenium deficiency have been mapped; worldwide and in them selenium supplementation has become an accepted practice.

ACKNOWLEDGEMENT:

A pleasant job remains to sit back and reflect on the pleasure and pains and acknowledge the efforts of all who helped to make this successful. I would like to acknowledge and my obligation to our principals Dr. K. S. Jain and Mr. G. M. Swami for providing the necessary facilities. I am one of the fortunate students whose path is enlightened by the expertise and guidance of Miss Rajani Nair. I would like to thank AJRC to give me opportunity for presenting review article regarding my interested topic. Lastly, I would like to express my gratitude to my parents who always supported and encouraged me. Thus I have solemnized my participation in this review with dedication to make it success.

REFERENCES:

1. National Research Council. Food and nutrition board recommended dietary allowances, National Academy Press, Washington, DC, 1989, 10^th ed.

2. Combs Jr. GF, Gray WP. Chemopreventive agents: selenium. Pharmacol Ther. 79; 1988: 179–92.

3. Neve J. Selenium as a risk factor for cardiovascular diseases. J Cardiovasc Risk. 3; 1996: 42–7.

4. Heliovaara M, Knekt P, Aho K, Aaran RK, Alfthan G, Aromaa A. Serum antioxidants and risk of rheumatoid arthritis. Ann Rheum Dis. 53; 1994: 51–3.

5. Look MP, Rockstroh JK, Rao GS, Kreuzer KA, Spengler U, Sauerbruch T. Serum selenium versus lymphocyte subsets and markers of disease progression and inflammatory response in human immunodefeciency virus-1 infection. Biol Trace Elem Res. 56 (1); 1997: 31–41.

6. Combs Jr. GF, Clark LC, Turnbull BW. Reduction of cancer risk with an oral supplement of selenium. Biomed Environ Sci. 10; 1997: 227–34.

7. Tapiero H, Townsend DM, Tew KD. The antioxidant role of selenium and seleno-compounds. Biomed Pharmacother. 57; 2003: 134–44.

8. Moser PB, Reynolds RD, Acharya S, Howard MP, Andon MB, Lewis SA. Copper, iron, zinc and selenium dietary intake and status of Nepalese lactating women and their breast-fed infants. Am J Clin Nutr. 47; 1988: 729–34.

9. Brown Jr., Robert D. "Mineral Commodity Survey 1997: Selenium". United States Geological Survey. 2009. http://minerals.usgs.gov/minerals/pubs/commodity/selenium/830398.pdf

10. Pennington JA and Young BE. Total diet study nutritional elements. J Am Diet Assoc. 91; 1991: 179-83.

11. http://www.nal.usda.gov/fnic/foodcomp

12. T. Zane Davis. "Selenium in Plants". 2008: 8. http://www.ars.usda.gov/SP2UserFiles/Place/54282000/PPClassPPSlides.

13. Burk RF. Molecular biology of selenium with implications for its metabolism. FASEB J. 9; 1991: 2274–9.

14. Bock A, Forchhammer K, Heider J, Leinfelder W, Sawers G, Veprek B, et al. Selenocysteine: the 21st amino acid. Mol Microbiol. 3; 1991: 515–20.

15. Tapiero H, Townsend DM, Tew KD. The antioxidant role of selenium and seleno-compounds. Biomed Pharmacother. 57; 2003: 134–44.

16. Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG. Selenium: biochemical role as a component of glutathione peroxidase. Science. 179; 1973: 588–90.

17. Kryukov GV, Castellano S, Novoselov SV, Lobanov AV, Zehtab O, Guigo´ R, et al. Characterization of mammalian selenopreteomes. Science. 300 (5624); 2003: 1439–43.

18. Ursini F, Maiorino M, Gregolin C. The selenoenzyme phospholipid hydroperoxide peroxidase. Biochim Biophys Acta. 839; 1985: 62–70.

19. Ghyselinck NB, Dufaure I, Lareyre JJ, Rigaudiere N, Mattei MG, Dufaure JP. Structural organization and regulation of the gene for the androgen-dependent.

20. Burk RF, Hill KE, Motley AK. Selenoprotein metabolism and function: evidence for more than one function for selenoprotein P. J Nutr. 133(5); 2003: 1517–20.

21. Kryukov GV, Kryukov VM, Gladyshev VN. New mammalian selenocysteine-containing proteins identied with an algorithm that searches for selenocysteine insertion sequence elements. J Biol Chem. 274; 1999: 33888–97.

22. Groff JL, Gropper SS, and Hunt SM. Microminerals. In: Advanced Nutrition and Human Metabolism. Minneapolis: West Publishing Company, Minneapolis. 1995: 381-384.

23. Ip C, Ganther HE. Relationship between the chemical form of selenium and anticarcinogenic activity. In: Wattenberg L, Lipkin M, Boone CW, Kelloff GJ, editors.

24. Sunde RA, Gutzke GE and Hoekstra WG. Effect of dietary methionine on the biopotency of selenite and selenomethionine in the rat. J. Nutr. Ill. 1981: 76-86.

25. Ashrafi MR, Shabanian R, Abbaskhanian A et al. Selenium and intractable epilepsy: Is there any correlation? Pediatr Neurol. 36 (1); 2007: 25-49.

26. Foster SJ, Kraus RJ et al., The metabolism of selenomethionine, Se-methylselenocysteine, their selenonium derivatives, and trimethylselenonium in the rat. Arch. Biochem. Biophys. 251; 1986: 77–86.

27. Ganther HE, Lawrence JR. Chemical transformations of selenium in living organisms. Improved forms of selenium for cancer prevention. Tetrahedron. 53; 1997: 12229–310.

28. Hsieh HS, Ganther HE. Acid-volatile selenium formation catalyzed by glutathione reductase. Biochemistry. 14; 1975: 1632–1636.

29. Dekkers JC, Van Doornen LJP and Kemper CG. The Role of Antioxidant Vitamins and Enzymes in the Prevention of Exercise-Induced Muscle Damage. Sports Med. 21; 1996: 213-238.

30. Spallholz JE. Free radical generation by selenium compounds and their prooxidant toxicity. Biomed. Environ. Sci. 10; 1997: 260–270.

31. Sigler K, Chaloupka, J, Brozmanov´a J, Stadle, N, Hofer,M. Oxidative stress in microorganisms. I. Microbial vs. higher cells damage and defenses in relation to cell aging and death. Folia Microbiol. 44; 1999: 587–624.

32. Valko M, Izakovic M, Mazur M, Rhodes CJ, Telser J. Role of oxygen radicals in DNA damage and cancer incidence. Mol. Cell. Biochem. 266; 2004: 37–56.

33. Spallholz JE. On the nature of selenium toxicity and carcinostatic activity. Free Radic. Biol. Med. 17; 1994: 45–64.

34. Spallholz JE, Palace VP, Reid TW. Methioninase and selenomethionine but not Se-methylselenocysteine generate methylselenol and superoxide in an in vitro chemiluminescent assay: implications for the nutritional carcinostatic activity of selenoamino acids. Biochem. Pharmacol. 67; 2004: 547–554.

35. Burk RF and Levander OA. Selenium In: Modern Nutrition in Health and Disease Ninth Edition, edited by M. Shils, J. Olson, M. Shike, and A. C. Ross. Baltimore: Williams & Wilkins, 1999, 265-276.

36. Burk RF. The significance of selenium levels in blood. In: Proceedings of the Symposium on Selenium-Tellurium in the Environment. 1976: 194-203.

37. Bardia A, Tleyjeh IM, Cerhan JR, et al. Efficacy of antioxidant supplementation in reducing primary cancer incidence and mortality: systematic review and meta-analysis. Mayo Clin Proc. 83(1); 2003: 23-34.

38. Duffield-Lillico AJ, Slate EH, Reid ME, et al. Selenium supplementation and secondary prevention of nonmelanoma skin cancer in a randomized trial. J Natl Cancer Inst. 95(19); 2003: 1477-1481.

39. Etminan M, FitzGerald JM, Gleave M, et al. Intake of selenium in the prevention of prostate cancer: a systematic review and meta-analysis. Cancer Causes Control. 16(9); 2005: 1125-31.

40. Hoque A, Albanes D, Lippman SM, et al. Molecular epidemiologic studies within the Selenium and Vitamin E Cancer Prevention Trial. Cancer Causes Control. 12(7); 2001: 627-33.

41. Hurwitz BE, Klaus JR, Llabre MM, et al. Suppression of human immunodeficiency virus type 1 viral load with selenium supplementation: a randomized controlled trial. Arch Intern Med. 167(2); 2007: 148-54.

42. Rayman M, Thompson A, Warren-Perry M, et al. Impact of selenium on mood and quality of life: a randomized, controlled trial. Biol Psychiatry. 59(2); 2006: 147-54.

43. Reid ME, Duffield-Lillico AJ, Sunga A, et al. Selenium supplementation and colorectal adenomas: an analysis of the nutritional prevention of cancer trial. Int J Cancer. 118(7); 2006: 1777-81.

44. Shaheen SO, Newson RB, Rayman MP, et al. Randomised, double blind, placebo-controlled trial of selenium supplementation in adult asthma. Thorax. 62(6); 2007: 483-90.

45. Stawicki SP, Lyons M, Aloupis M, et al. Current evidence from phase III clinical trials of selenium supplementation in critically Ill patients: why should we bother? Mini Rev Med Chem. 7(7); 2007: 693-9.

46. Stranges S, Marshall JR, Natarajan R, et al. Effects of long-term selenium supplementation on the incidence of type 2 diabetes: a randomized trial. Ann Intern Med. 147(4); 2007: 217-23.

47. Stranges S, Marshall JR, Trevisan M, et al. Effects of selenium supplementation on cardiovascular disease incidence and mortality: secondary analyses in a randomized clinical trial. Am J Epidemiol. 163(8); 2006: 694-9.

48. Turker O, Kumanlioglu K, Karapolat I, et al. Selenium treatment in autoimmune thyroiditis: 9-month follow-up with variable doses. J Endocrinol. 190(1); 2006: 151-6.

49. You WC, Brown LM, Zhang L, et al. Randomized double-blind factorial trial of three treatments to reduce the prevalence of precancerous gastric lesions. J Natl Cancer Inst. 98(14); 2006: 974-83.

50. Lippman SM, Klein EA, Goodman PJ, Lucia MS, Thompson IM, Ford LG, et al. The effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial. JAMA. 301; 2009: 39-51.

51. Ozer NK, Boscoboinik D, Azzi A. New roles of low density lipoproteins and vitamin E in the pathogenesis of atherosclerosis. Biochem Mol Biol Int. 35; 1995: 117-24.

52. Lapenna D, de Gioia S, Ciofani G, Mezzetti A, Ucchino S, Calafiore AM, Napolitano AM, Di Ilio C, Cuccurulo F. Glutathione-related antioxidant defenses in human atherosclerotic plaques. Circulation. 97; 1998: 1930-4.

53. Neve J. Selenium as a risk factor for cardiovascular diseases. J Cardiovasc Risk. 3; 1996: 42-7.

54. Combs GF, Clark LC, Turnbull BW. An analysis of cancer prevention by selenium. BioFactors. 14; 2001: 153-9.

55. Look MP, Rockstroh JK, Rao GS, Kreuzer KA, Spengler U, Sauerbruch T. Serum selenium versus lymphocyte subsets and markers of disease progression and inflammatory response in human immunodeficiency virus-1 infection. Biol Trace Elem Res. 56(1); 1997: 31-41.

56. Singhal N and Austin J. A clinical review of micronutrients in HIV infection. J Int Assoc Physicians AIDS Care. 1; 2002: 63-75.

57. Romero-Alvira D and Roche E. The keys of oxidative stress in acquired immune deficiency syndrome apoptosis. Medical Hypotheses. 51(2); 1998: 169-73.

58. Patrick L. Nutrients and HIV; Part One - Beta carotene and selenium. Altern Med Rev. 4; 1999: 403-13.

59. Grimble RF. Nutritional antioxidants and the modulation of inflammation: Theory and practice. New Horizons. 2; 1994: 175-85.

60. Aaseth J, Haugen M, Forre O. Rheumatoid arthritis and metal compounds- perspectives on the role of oxygen radical detoxification. Analyst. 123; 1998: 3-6.

61. Selenium. In: Dietary Reference Intakes for Ascorbic acid, Vitamin E, Selenium, and Carotenoids. Food and Nutrition Board, Institute of Medicine. National Academy Press, Washington DC. 7; 2000: 284-324.

62. Ravaglia et al. "Effect of micronutrient status on natural killer cell immune function in healthy free-living subjects aged >=90 y1". American Journal of Clinical Nutrition. 71 (2); 2000: 590–598.

63. MedSafe Editorial Team. "Selenium". Prescriber Update Articles. New Zealand Medicines and Medical Devices Safety Authority. http://www.medsafe.govt.nz/Profs/PUarticles/Sel.htm.

64. Essensial of Human Nutrition, Mann and Truswell, Oxford University Press, 2002. 2^nd ed.

65. http://www.dheausa.com/

Received on 15.03.2012 Modified on 25.03.2012

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