The Central Role of Metal Coordination in Selenium Antioxidant Activity

Abstract

Oxidative DNA damage occurs in vivo by hydroxyl radical generated in metal-mediated Fenton-type reactions. Cell death and mutation caused by this DNA damage are implicated in neurodegenerative and cardiovascular diseases, cancer, and aging. Treating these conditions with antioxidants, including highly potent selenium antioxidants, is of growing interest. Gel electrophoresis was used to directly quantify DNA damage inhibition by selenium compounds with copper and H(2)O(2). Selenocystine inhibited all DNA damage at low micromolar concentrations, whereas selenomethionine showed similar inhibition at 40 times these concentrations, and 2-aminophenyl diselenide showed no effect. DNA damage inhibition by these selenium compounds does not correspond to their glutathione peroxidase activities, and UV-vis and gel electrophoresis results indicate that selenium-copper coordination is essential for DNA damage inhibition. Understanding this novel metal-coordination mechanism for selenium antioxidant activity will aid in the design of more potent antioxidants to treat and prevent diseases caused by oxidative stress.

Selenium: its role as antioxidant in human health

“…The effectiveness of Se in the prevention of DNA damage, however, depends on its chemical forms. In an in vitro study, Battin et al [55] found that selenocysteine inhibited DNA damage more strongly than the selenomethionine. Other possible anticancer mechanisms of Se include the induction of apoptosis, cell-cycle arrest and DNA-repair genes, inhibition of protein kinase C activity and cell growth and effect on estrogen-and androgen-receptor expression [49,52,56].…”

Resistin decreases expression of endothelial nitric oxide synthase through oxidative stress in human coronary artery endothelial cells

“…SeMet participates in an intramolecular transsulfuration reaction, forming selenocystein, which, in turn, increases the activity of internal antioxidant enzymes GPX and thioredoxin reductase (1). In addition, SeMet is able to directly interact with some oxidant molecules or oxidant-generating ions (3,43). Ginsenosides act as antioxidants by increasing internal antioxidant enzymes and acting as free-radical scavengers (11,34,48,52).…”

DNA-bound metal ions: recent developments

“…The organoselenium compounds selenocysteine and selenomethionine function as antioxidants in reactions involving Cu(I) through coordinating the Cu ions (55,56). Methyl-selenocysteine exhibited the ability to minimize oxidative DNA damage by coordinating both Cu(I) and Fe(II), and whereas selenocystamine exhibited antioxidant activity for reactions involving both Cu(I) and Fe(II), there was evidence that it formed a coordination complex only with Fe(II) (56).…”