SUPPRESSION OF NITRIC-OXIDE TOXICITY IN ISLET CELLS BY ALPHA-TOCOPHEROL

We show here that preincubation of pancreatic islet cells with alpha-tocopherol significantly improves their resistance to toxic doses of nitric oxide (NO). No protection was afforded by other antioxidants such as vitamin C or glutathione-monoethyl ester, The pathway of NO induced islet cell death involves DNA damage and excessive activation of poly(ADP-ribose)polymerase leading to irreversible depletion of intracellular NAD(+). alpha-Tocopherol was found to interfere at early steps of this pathway, by preventing the occurrence of DNA strand breaks. This indicates that alpha-tocopherol directly interacts with NO or its reactive intermediates. We conclude that alpha-tocopherol is not only part of the cellular defence system against oxygen radicals but also protects eukaryotic cells from NO toxicity.