DNA-DAMAGE IN THE KIDNEYS OF DIABETIC RATS EXHIBITING MICROALBUMINURIA

8-Hydroxydeoxyguanosine (8-OHdG), an oxygen radical induced modification of purine residue in DNA, was measured in the liver, pancreas, and kidney of streptozotocin-induced diabetic rats (STZR) exhibiting microalbuminuria. At 4 weeks after the injection of streptozotocin (50 mg/kg, IV), the rate of urinary albumin excretion was 0.5+/-0.1 and 2.0+/-0.2 mg/24 h in age-matched control rats (C) and STZR, respectively. Compared to CR: STZR also showed a significantly increased level of 8-OHdG in the kidney but not the liver and pancreas. Amounts of 8-OHdG/10(5) dG for CR and STZR were 3.4+/-0.3 and 5.1+/-0.2 for renal cortices, and 4.1+/-0.2 and 20.0+/-3.7 for renal papillae. Daily injection of insulin (2U, SC) starting on the third day after streptozotocin treatment significantly reduced both urinary albumin excretion and papillary 8-OHdG formation, which suggests that these are associated with the diabetic state induced by streptozotocin rather than a direct nephrotoxic effect of the drug. This study suggests that formation of 8-OHdG and, therefore, oxidative damage are closely related in the process of diabetic nephropathy.