Suppression of nitric oxide toxicity in islet cells by α‐tocopherol

Abstract
We show here that preincubation of pancreatic islet cells with α‐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+. α‐Tocopherol was found to interfere at early steps of this pathway, by preventing the occurrence of DNA strand breaks. This indicates that α‐tocopherol directly interacts with NO or its reactive intermediates. We conclude that α‐tocopherol is not only part of the cellular defence system against oxygen radicals but also protects eukaryotic cells from NO toxicity.