Actions of Thiols, Persulfides, and Polysulfides as Free Radical Scavenging Antioxidants

SIGNIFICANCE: The essential roles of thiol compounds as redox signaling mediators and protectors have been established. Recently, the roles of persulfides and polysulfides as mediators involved in numerous physiological processes have been revealed. RECENT ADVANCES: Recently, it became possible to detect and measure persulfides and polysulfides in human fluids and tissues and their physiological functions, including cellular signaling and protection against oxidative stress, have been reported, but the underlying mechanisms and dynamics remain elusive. CRITICAL ISSUES: Physiological functions of thiol compounds have been studied, focusing primarily on two-electron redox reactions. In contrast, the contribution of one-electron redox mechanisms, that is, free radical-mediated oxidation and antioxidation, has received much less attention. Considering the important effects of free radical-mediated oxidation of biological molecules on pathophysiology, the antioxidant functions of thiol compounds as free radical scavengers are challenging issues. FUTURE DIRECTIONS: The antioxidant actions and dynamics of thiols, hydropersulfides, and hydropolysulfides as free radical scavenging antioxidants and their physiological significance remain to be established. Antioxid. Redox Signal. 39, 728–743.