Identification of dihydropyrazine-glutathione adducts

Dihydropyrazines (DHPs) are glycation intermediates generated both in vivo and in food. DHPs can lead to the formation of a variety of different radical species, which can lead to DNA damage and enzyme inhibition. In addition, the presence of DHPs can lead to a decrease in cellular glutathione (GSH) levels, and induce the expression of antioxidant genes. In this study, the products resulting from the reaction of DHP with GSH have been analyzed in detail, with some of the products being separated by reversed-phase HPLC. The structures of the isolated DHP-GSH adducts were determined by FAB-MS and NMR analyses. These data suggested that the reaction of DHP with a thiol moiety could be involved in oxidative stress, because an increase in the amount of DHP-GSH adducts would result in a decrease in the cellular GSH levels.