Hydroxyl radical formation in diabetic rats induced by streptozotocin.

Production of hydroxyl radicals was examined in the diabetic rats induced by streptozotocin to prove its involvement to the pathogenesis of diabetes. Hydroxyl radicals generated in plasma, heart muscle, liver and brain of the hyperglycemic rats were quantitatively assayed by trapping hydroxyl radicals with salicylic acid as 2,3- and 2,5-dihydroxybenzoic acid. The concentrations of 2,3- and 2,5-dihydroxybenzoic acid were significantly increased in all the tissues of the diabetic rats. In the brain and heart muscle of the diabetic rats, the increase of 2,3-dihydroxybenzoic acid was more manifest than that of 2,5-dihydroxybenzoic acid, while in liver 2,5-dihydroxybenzoic acid increased markedly. All the values of 2,3-dihydroxybenzoic acid detected in the tissues of the diabetic rats were quite higher than those in control. Hydroxyl radical production and blood glucose concentration were depended almost linearly on the amount of streptozotocin injected to rats up to 60 mg/kg body weight. It was suggested that 2,3-dihydroxybenzoic acid was produced from hydroxyl radicals themselves, while 2,5-dihydroxybenzoic acid was produced by hydroxylation of salicylic acid not only with hydroxyl radicals, but also by enzymatic reaction of microsomal cytochrome-P450. Hydroxyl radical formation may account for some pathological process especially in the heart muscle and brain.