LAZAROID ANTIOXIDANT REDUCES INCIDENCE OF DIABETES AND INSULITIS IN NONOBESE DIABETIC MICE

Oxygen free radicals have been implicated as mediators of pancreatic islet beta cell damage in autoimmune, insulin-dependent diabetes mellitus (IDDM). We examined the effects of a potent antioxidant compound, U78518F, on the incidence of diabetes and pancreatic islet infiltration with lymphocytes and monocytes (insulitis) in the nonobese diabetic (NOD) mouse, an animal model for human IDDM. U78518F, administered to NOD mice from age 8 to 30 weeks, produced a dose-dependent decrease in diabetes incidence, from 89% (16/18 control NOD mice) to 61% (11/18 NOD mice treated with 2 mg/kg/day U78518F, p < 0.05) and 44% (8/18 NOD mice treated with 16 mg/kg/day U78518F, p < 0.005). Protection against diabetes was associated with significant decreases in pancreatic insulitis and prevention of beta cell loss in the U78518F-treated NOD mice. These results suggest that antioxidants may have therapeutic application in attempts to prevent immune-mediated islet beta cell damage and IDDM.