Intracellular glutathione production, but not protein glycation, underlies the protective effects of captopril against 2-deoxy-D-ribose-induced ß-cell damage.

Our previous study reported that both oxidative stress and protein glycation were the principal mechanisms underlying 2­deoxy­D­ribose (dRib)­induced pancreatic ß­cell damage. The aim of the present study was to investigate the effects of captopril on dRib­induced damage in pancreatic ß­cells, as well as to determine the mechanisms underlying these effects. Treatment with dRib increased the levels of cytotoxicity, apoptosis, and intracellular reactive oxygen species in Syrian hamster insulinoma HIT­T15 cells; however, pretreatment with captopril significantly inhibited the effects of dRib. The intracellular levels of reduced and oxidized glutathione were depleted following treatment with dRib; however, these levels were restored following HIT­T15 cell treatment with captopril. In rat islets, dRib stimulation suppressed the mRNA expression levels of insulin, and pancreatic and duodenal homeobox 1, as well as insulin content; however, these effects were dose­dependently reversed by treatment with captopril. Treatment with buthionine sulfoximine, an inhibitor of intracellular glutathione biosynthesis, inhibited the protective effects of captopril on dRib­mediated glutathione depletion and cytotoxicity in HIT­T15 cells. Following incubation with albumin, dRib increased the formation of dicarbonyl and advanced glycation end products. Treatment with captopril did not inhibit the dRib­induced increase in production of dicarbonyl and advanced glycation end products. In conclusion, treatment with captopril reversed dRib­induced oxidative damage and suppression of insulin expression in ß­cells. The mechanism underlying the protective effects of captopril may involve increased intracellular glutathione production, rather than protein glycation.