Oxidation of Hydrogen Sulfide by Quinones: How Polyphenols Initiate Their Cytoprotective Effects

We have shown that autoxidized polyphenolic nutraceuticals oxidize H(2)S to polysulfides and thiosulfate and this may convey their cytoprotective effects. Polyphenol reactivity is largely attributed to the B ring, which is usually a form of hydroxyquinone (HQ). Here, we examine the effects of HQs on sulfur metabolism using H(2)S- and polysulfide-specific fluorophores (AzMC and SSP4, respectively) and thiosulfate sensitive silver nanoparticles (AgNP). In buffer, 1,4-dihydroxybenzene (1,4-DB), 1,4-benzoquinone (1,4-BQ), pyrogallol (PG) and gallic acid (GA) oxidized H(2)S to polysulfides and thiosulfate, whereas 1,2-DB, 1,3-DB, 1,2-dihydroxy,3,4-benzoquinone and shikimic acid did not. In addition, 1,4-DB, 1,4-BQ, PG and GA also increased polysulfide production in HEK293 cells. In buffer, H(2)S oxidation by 1,4-DB was oxygen-dependent, partially inhibited by tempol and trolox, and absorbance spectra were consistent with redox cycling between HQ autoxidation and H(2)S-mediated reduction. Neither 1,2-DB, 1,3-DB, 1,4-DB nor 1,4-BQ reduced polysulfides to H(2)S in either 21% or 0% oxygen. Epinephrine and norepinephrine also oxidized H(2)S to polysulfides and thiosulfate; dopamine and tyrosine were ineffective. Polyphenones were also examined, but only 2,5-dihydroxy- and 2,3,4-trihydroxybenzophenones oxidized H(2)S. These results show that H(2)S is readily oxidized by specific hydroxyquinones and quinones, most likely through the formation of a semiquinone radical intermediate derived from either reaction of oxygen with the reduced quinones, or from direct reaction between H(2)S and quinones. We propose that polysulfide production by these reactions contributes to the health-promoting benefits of polyphenolic nutraceuticals.