SPIN-TRAPPING AGENT PHENYL N-TERT-BUTYLNITRONE PROTECTS AGAINST THE ONSET OF DRUG-INDUCED INSULIN-DEPENDENT DIABETES-MELLITUS

Insulin-dependent diabetes mellitus is an autoimmune disease believed to be caused by an inflammatory process in the pancreas leading to sel ective destruction of the beta-cells. Cytokines and nitric oxide (NO) have been shown to be involved in this destruction. Phenyl N-tert-buty lnitrone (PBN) has demonstrated protective effects against several pat hological conditions including ischemia-reperfusion injury and endotox in-induced shock, We report here that PBN co-administration can preven t the onset of the STZ-induced diabetes in mice. PBN co-treatment inhi bited the streptozotocin (STZ)-induced hyperglycemia, the elevation in the level of glycated hemoglobin and weight loss in the treated mice, Histological observations indicated destruction of beta-cells in the STZ-treated animals and its prevention by PBN co-treatment. EPR spin t rapping experiments in the pancreas indicated the in vivo formation of NO in STZ-treated animals and its attenuation by PBN treatment. (C) 1 997 Federation of European Biochemical Societies.