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, i.v.), the rate of urinary albumin excretion was 0.5 +/- 0.1 and 2.0 +/- 0.2 mg/24 h in age-matched control rats (CR) 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 (2 U, 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.
Ha
H
H
Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea.
Kim
C
C
Son
Y
Y
Chung
M H
MH
Kim
K H
KH
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000419:Albuminuria; D000818:Animals; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000473:pathology; D005609:Free Radicals; D007672:Kidney Cortex / Q000378:metabolism / Q000473:pathology; D007679:Kidney Medulla / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D009928:Organ Specificity; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values
D005609:Free Radicals; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine