OH-Radical Specific Addition to Glutathione S-Atom at the Air-Water Interface: Relevance to the Redox Balance of the Lung Epithelial Lining Fluid

Antioxidants in epithelial lining fluids (ELF) prevent inhaled air pollutants from reaching lung tissue. This process, however, may upset ELF's redox balance, which is deemed to be expressed by the ratio of the major antioxidant glutathione (GSH) to its putative oxidation product GSSG. Previously, we found that at physiological pH O-3(g) rapidly oxidizes GS(2-)(aq) (but not GSH(-)) to GSO(3)(-) rather than GSSG. Here, we report that in moderately acidic pH <= 5 media center dot OH(g) oxidizes GSH(-)(aq) to sulfenic GSOH(-), sulfinic GSO(2)(-), and sulfonic GSO(3)(-) acids via center dot OH specific additions to reduced S-atoms. The remarkable specificity of center dot OH on water versus its lack of selectivity in bulk water implicates an unprecedented steering process during [OH...GSH] interfacial encounters. Thus, both O-3 and center dot OH oxidize GSH to GSOH(-) under most conditions, and since GSOH(-) is reduced back to GSH in vivo by NADPH, redox balance may be in fact signaled by GSH/GSOH ratios.