Effects of insulin and antioxidant on plasma 8-hydroxyguanine and tissue 8-hydroxydeoxyguanosine in streptozotocin-induced diabetic rats.
Cumulating evidence suggests that enhanced oxidative stress may contribute to diabetic angiopathy. The levels of 8-hydroxydeoxyguanosine (8-OHdG) and 8-hydroxyguanine (8-OHG), indicators of oxidative DNA damage, in tissue or body fluid are increased in diabetic patients. However, it is unclear whether plasma 8-OHG correlates with tissue 8-OHdG and whether insulin or antioxidant treatment reduces plasma 8-OHG in diabetic state. In this study, we measured the 8-OHG levels in plasma as well as the 8-OHdG levels in liver and kidney in streptozotocin-induced diabetic rats (DR) treated with insulin (DR+I), insulin and probucol (DR+I/P), or insulin and vitamin E (DR+I/E). There was a correlation between plasma 8-OHG levels and tissue 8-OHdG levels (plasma 8-OHG vs. liver 8-OHdG: r = 0.64, P < 0.001; plasma 8-OHG vs. kidney 8-OHdG: r = 0.38, P = 0.06). DR had levels of plasma 8-OHG that were three times higher than control rats (CR), whereas they had levels of tissue 8-OHdG that were approximately 1.5-2 times higher. Plasma 8-OHG levels in DR were almost normalized by insulin treatment, although insulin partially corrected hyperglycemia (plasma 8-OHG: CR 3.3 +/- 2.7 pmol/ml; DR 10.4 +/- 2.3 pmol/ml, P < 0.05 vs. CR; DR with insulin 3.6 +/- 1.0 pmol/ml, P < 0.05 vs. DR). However, tissue 8-OHdG levels in DR were significantly decreased by combined treatment with insulin and antioxidant (probucol or vitamin E), but not by insulin treatment alone. This data suggests that plasma 8-OHG could be a useful biomarker of oxidative DNA damage in diabetic subjects. The mechanism of differential response of plasma 8-OHG and tissue 8-OHdG to insulin and antioxidant treatment remains to be elucidated.
Park
K S
KS
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Kim
J H
JH
Kim
M S
MS
Kim
J M
JM
Kim
S K
SK
Choi
J Y
JY
Chung
M H
MH
Han
B
B
Kim
S Y
SY
Lee
H K
HK
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D006147:Guanine / Q000031:analogs & derivatives* / Q000097:blood*; D007328:Insulin / Q000494:pharmacology* / Q000627:therapeutic use; D007668:Kidney / Q000737:chemistry; D008099:Liver / Q000737:chemistry; D008297:Male; D018384:Oxidative Stress; D011341:Probucol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D014810:Vitamin E; C024829:8-hydroxyguanine; D006147:Guanine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D011341:Probucol