5] Perthiols as antioxidants: Radical-scavenging andprooxidative mechanisms

Abstract

Publisher Summary Thiols (RSH) are recognized for their radical-scavenging role in protection against cellular oxidative stress and in the repair of radical-induced DNA damage. The administration of exogenous thiol drugs offers defense against many free radical–associated diseases and protects normal tissues in cancer therapy using radiation or drugs. The antioxidant efficiency of perthiols reflects the free radical-scavenging ability of perthiols and prooxidative effects associated with perthiyl radical (RSS) formation. The methods used for investigating thiol free radical reactivity can be equally applied to assess the radical-scavenging and prooxidative properties of perthiols. Pulse radiolysis has proved to be a useful tool to quantify the free radical–scavenging ability of perthiols. Chemical models have been designed to probe the interaction of perthiols with free radical species commonly associated with cellular oxidative stress and to elucidate subsequent prooxidative reactions. The free radical–scavenging reactions of perthiols are qualitatively similar to, but quantitatively different from, those of the corresponding thiol antioxidants. Perthiols are not only more efficient hydrogen donors than thiols, but as perthiolate anions they are highly efficient electron donors. The antioxidant-derived radical, in this case the perthiyl radicals, are significantly less reactive than their thiyl radical counterparts and are less likely to pose a threat if generated within the cellular environment. In view of the essential role thiols play in controlling cellular oxidative stress, the encouraging performance of perthiols as free radical scavengers suggests they will be of use as exogenous antioxidants.