Effects of Insulin and Antioxidant on Plasma 8-Hydroxyguanine and Tissue 8-Hydroxydeoxyguanosine in Streptozotocin-Induced Diabetic Rats

Abstract

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 ϳ1.5-2 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.

The pathogenesis of diabetic complications: the role of DNA injury and poly(ADP-ribose) polymerase activation in peroxynitrite-mediated cytotoxicity

“…The role of hyperglycemia-induced oxidative stress in producing DNA damage is also supported by recent findings showing that increased amounts of 8-hydroxyguanine and 8-hydroxydeoxy guanosine (markers of oxidative damage to DNA) can be found in both the plasma and tissues of streptozotocin diabetic rats (Park et al 2001). Base modifications and DNA strand breaks have been demonstrated in diabetic patients as well (Lorenzi et al 1987, Anderson et al 1998, Astley et al 1999, Sardas et al 2001, Dincer et al 2003.…”

Influence of pyridoxylidene aminoguanidine on biomarkers of the oxidative stress and selected metabolic parameters of rats with diabetes mellitus

“…Increased levels of 8-oxodG was found in urine, mononuclear cells and skeletal muscles of diabetic patients Suziki et al 1999;Wu et al 2004). In rats with streptozotocine-induced DM increased concentrations of 8-oxodG were found, for example in plasma, liver, kidneys and β-cells of pancreas (Ihara et al 1999;Park et al 2001).…”

Hyperglycemia induces apoptosis in rat liver through the increase of hydroxyl radical: new insights into the insulin effect

“…The initial cellular response to high glucose challenge is the generation of ROS, which rapidly induces apoptotic cell death (Park et al 2001).…”