Preparation of Oligoselenodiglutathiones and Their Suppressive Effects on Oxidative DNA Damage Induced by Catechol and Copper

We previously reported that novel polyselenodithiols are produced along with selenotrisulfide when a thiol (Penicillamine) is reacted with selenite (H2SeO3). Here, we report the production of oligoselenodiglutathiones and their suppressive effects on oxidative DNA damage. Oligoselenodiglutathiones were produced by exceeding the conventional reaction ratio of [H2SeO3]/[glutathione (GSH)] = 1/4. In liquid chromatography-mass spectrometry (LC/MS) analysis, the observed isotope patterns showed good agreement with the calculated isotope patterns assuming that two, three, or four selenium (Se) atoms were incorporated in the molecules. Based on H-1 NMR and MS data, the structures of oligoselenodiglutathiones were assumed to have a common symmetrical structure that was centered by linearly bound Se atoms "wedged" in the disulfide bond of two GSH molecules. At 8 mu M, selenodiglutathione (GSSeSG) and diselenodiglutathione (GSSe(2)SG) showed 80% suppression of the formation of 8-oxo-7,8-dihydroxy-2'-deoxyguanosine (in calf thymus DNA) induced by carcinogenic catechol and copper. The suppressive effects of GSSeSG and GSSe(2)SG were around threefold higher than that of glutathione disulfide at the same concentration, and the suppressive effect was not observed for H2SeO3 or GSH. Thus, formation of oligoselenodiglutathiones is important for Se or GSH to exert its protective effects on biomolecules from oxidative damage.