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Nitric oxide (NO) generated by diethylamine nonoate (DEA/NO), an NO donor, readily oxidized the free sulfhydryl group of human serum albumin (HSA) as well as the sulfhydryl groups of reduced glutathione (GSH) and dithiothreitol (DTT) at pH 7.4 and 37 degrees C. Under anaerobic conditions, the major products of the oxidation of HSA thiol by NO were the sulfenic acid (RSOH) of HSA and nitrous oxide (N2O). The stoichiometry for this reaction, viz., 1 mol of HSA sulfhydryl oxidized to 1 mol of N2O produced, is consistent with a net two-electron oxidation of the protein thiol to a sulfenic acid. The sulfenic acid product of HSA was shown to react with dimedone and GSH, two known reactions of sulfenic acids. In contrast, anaerobic oxidation of GSH and DTT by NO gave a stoichiometry close to the expected ratio of 2:1 (sulfhydryl oxidized to N2O produced) for the oxidation of these thiols to their disulfides and N2O. Under aerobic conditions, significant fractions of the sulfhydryl groups of HSA, GSH, and DTT were oxidized to their respective thionitrites, presumably by N2O3. Thionitrite formation was not observed in the absence of oxygen. The production of HSA-sulfenic acid by NO, as well as by other oxidizing agents such as H2O2 and peroxynitrite, followed by its reaction with circulating GSH or L-Cys may account for the mixed disulfides of HSA observed in plasma.

The effect of several antioxidants and cysteine‐elevating precursor drugs (prodrugs) was tested on lens damage occurring after in vitro exposure to low levels of 60Co‐y‐irradiation, to simulate in vitro the exposure to radiation in vivo of (1) astronauts (2) jet crews (3) military radiation accident personnel. Tocopherol (100 μM), ascorbic acid (1mM), R‐α‐lipoic acid (1mM), and taurine (0.5 mM) protected against radiation‐ associated protein leakage. MTCA and ribocysteine protected lenses against opacification, LDH and protein leakage, indicating that antioxidants and prodrugs of cysteine appear to offer protection against lens damage caused by low level radiation.

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