Polysulfides and products of HS/S-nitrosoglutathione in comparison to HS, glutathione and antioxidant Trolox are potent scavengers of superoxide anion radical and produce hydroxyl radical by decomposition of HO.

Exogenous and endogenously produced sulfide derivatives, such as HS/HS/S, polysulfides and products of the HS/S-nitrosoglutathione interaction (S/GSNO), affect numerous biological processes in which superoxide anion (O) and hydroxyl (OH) radicals play an important role. Their cytoprotective-antioxidant and contrasting pro-oxidant-toxic effects have been reported. Therefore, the aim of our work was to contribute to resolving this apparent inconsistency by studying sulfide derivatives/free radical interactions and their consequent biological effects compared to the antioxidants glutathione (GSH) and Trolox. Using the electron paramagnetic resonance (EPR) spin trapping technique and O, we found that a polysulfide (NaS) and S/GSNO were potent scavengers of O and cPTIO radicals compared to HS (NaS), GSH and Trolox, and S/GSNO scavenged the DEPMPO-OH radical. As detected by the EPR spectra of DEPMPO-OH, the formation of OH in physiological solution by S/GSNO was suggested. All the studied sulfide derivatives, but not Trolox or GSH, had a bell-shaped potency to decompose HO and produced OH in the following order: S/GSNO > NaS ≥ NaS > GSH = Trolox = 0, but they scavenged OH at higher concentrations. In studies of the biological consequences of these sulfide derivatives/HO properties, we found the following: (i) S/GSNO alone and all sulfide derivatives in the presence of HO cleaved plasmid DNA; (ii) S/GSNO interfered with viral replication and consequently decreased the infectivity of viruses; (iii) the sulfide derivatives induced apoptosis in A2780 cells but inhibited apoptosis induced by HO; and (iv) NaS modulated intracellular calcium in A87MG cells, which depended on the order of NaS/HO application. We suggest that the apparent inconsistency of the cytoprotective-antioxidant and contrasting pro-oxidant-toxic biological effects of sulfide derivatives results from their time- and concentration-dependent radical production/scavenging properties and their interactions with O, OH and HO. The results imply a direct involvement of sulfide derivatives in O and HO/OH free radical pathways modulating antioxidant/toxic biological processes.