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 H₂O₂. 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.