Selenium-based pharmacological agents: an update

The biochemistry and pharmacology of selenium is a subject of intense current interest, particularly from the viewpoint of public health. Selenium, long recognised as a dietary antioxidant, is now known to be an essential component of the active sites of several enzymes, including glutathione peroxidase and thioredoxin reductase, which catalyse reactions essential to the protection of cellular components against oxidative and free radical damage. A low concentration of selenium in plasma has been identified as a risk factor for several diseases, including cancer, cardiovascular disease, osteoarthritis and AIDS, and several large-scale selenium supplementation human trials are now underway. Evidence is emerging that, at least in the case of cancer, the antitumorigenic effect of selenium supplementation arises at least in part from enhanced production of specific selenium-containing metabolites, not just from maximal expression of selenoenzymes. Therefore a number of novel pharmaceutical agents which are selenium-based or which target specific aspects of selenium metabolism are under development. Among these are orally-active antihypertensive agents, anticancer, antiviral, immunosuppressive and antimicrobial agents, and organoselenium compounds which reduce oxidative tissue damage and edema. It can be anticipated that as our understanding of the basic biology and biochemistry of selenium increases, the coming years will bring further development of new selenium-based pharmaceutical agents with therapeutic potential toward a variety of human diseases.