Inxight Drugs

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Status:

Other

Class (Stereo):

CHEMICAL (ACHIRAL)

SELENIUM

MORE DETAILS

H6241UJ22B

Status:

Possibly Marketed Outside US

First approved in 1996

Class (Stereo):

CHEMICAL (ACHIRAL)

Selenium (Se) is mineral that is found in soil and occurs naturally in certain foods (such as whole grains, Brazil nuts, sunflower seeds, and seafood). Selenium, which is nutritionally essential for humans, is a constituent of more than two dozen sel...

enoproteins that play critical roles in reproduction, thyroid hormone metabolism, DNA synthesis, and protection from oxidative damage and infection. Selenium is used to treat or prevent selenium deficiency. Selenium deficiency produces biochemical changes that might predispose people who experience additional stresses to develop certain illnesses. For example, selenium deficiency in combination with a second stress (possibly a viral infection) leads to Keshan disease, a cardiomyopathy that occurred in parts of China prior to a government-sponsored selenium supplementation program that began in the 1970s. Before the Chinese government supplementation program, adults in the Keshan disease areas had average selenium intakes of no more than 11 mcg/day; intakes of at least 20 mcg/day protect adults from Keshan disease. Selenium has been used in alternative medicine as an aid to treat Hashimoto's thyroiditis, and to treat high cholesterol. Selenium is an important enzyme in the prevention of cellular damage by free radicals and reactive oxygen species. Selenium is first metabolized to selenophosphate and selenocysteine. Selenium incorporation is genetically encoded through the RNA sequence UGA. This sequence is recognized by RNA ste loop structures called selenocysteine inserting sequences (SECIS). These structures require the binding of SECIS binding proteins (SBP-2) to recognize selenocystiene. The specialized tRNA is first bound to a serine residue which is then enzymatically processed to a selylcysteyl-tRNA by selenocystiene sythase using selenophosphate as a selenium donor. Other unidentified proteins are required as part of the binding of this tRNA to the ribosome. Numerous studies in animal models and more recent studies in humans have demonstrated cancer chemopreventive effects with Se. There is extensive evidence that monomethylated forms of Se are critical metabolites for chemopreventive effects of Se. Induction of apoptosis in transformed cells is an important chemopreventive mechanism. Apoptosis can be triggered by micromolar levels of monomethylated forms of Se independent of DNA damage and in cells having a null p53 phenotype. Cell cycle protein kinase cdk2 and protein kinase C are strongly inhibited by various forms of Se. Inhibitory mechanisms involving modification of cysteine residues in proteins by Se have been proposed that involve formation of Se adducts of the selenotrisulfide (S-Se-S) or selenenylsulfide (S-Se) type or catalysis of disulfide formation. Selenium may facilitate reactions of protein cysteine residues by the transient formation of more reactive S-Se intermediates. A novel chemopreventive mechanism is proposed involving Se catalysis of reversible cysteine/disulfide transformations that occur in a number of redox-regulated proteins, including transcription factors. A time-limited activation mechanism for such proteins, with deactivation facilitated by Se, would allow normalization of critical cellular processes in the early stages of transformation. Randomized controlled trials of selenium supplementation for cancer prevention have yielded conflicting results. In 2003, the FDA allowed a qualified health claim on foods and dietary supplements containing selenium to state that while “some scientific evidence suggests that consumption of selenium may reduce the risk of certain forms of cancer… FDA has determined that this evidence is limited and not conclusive”. Selenium is available in multivitamin/multimineral supplements and as a stand-alone supplement, often in the forms of selenomethionine or of selenium-enriched yeast (grown in a high-selenium medium) or as sodium selenite or sodium selenate.