DNA oxidation and superoxide dismutase in the kidney of diabetic animals: effects of pioglitazone and repaglinide

Abstract

AbstractIn the present study, DNA oxidative damage was elevated and superoxide dismutase (Cu,Zn-SOD) metabolism was disturbed in the kidney of alloxan-induced diabetic animals. The effects of pioglitazone and repaglinide, new oral antidiabetics, on 8-hydroxy-2′-deoxyguanosine (8-OHdG) and Cu,Zn-SOD were studied. Diabetic versus control levels (mean ± SE) of 8-OHdG were 24.9 ± 0.2 vs. 21.8 ± 0.1 and 21.5 ± 0.2 vs 20.1 ± 0.2 pmol/µg DNA after 4 and 8 weeks, respectively. At p<0.05, pioglitazone diminished this parameter in diabetic animals (22.0 ± 0.2 and 20.1 ± 0.3 pmol/µg DNA). The level was not affected in diabetic groups receiving repaglinide (24.9 ± 0.2 and 21.5 ± 0.3 pmol/µg DNA). In diabetic kidney, Cu,Zn-SOD mRNA was diminished relative to control animals and was modulated by pioglitazone and repaglinide treatments. Simultaneously, Cu,Zn-SOD activity was also diminished (1.5 ± 0.2 vs. 2.8 ± 0.3 and 1.8 ± 0.1 vs 2.9 ± 0.3 U/mg protein after 4 and 8 weeks, respectively) and partly changed after pioglitazone (2.1 ± 0.4 and 2.3 ± 0.3 U/mg protein) and repaglinide (2.0 ± 0.1 and 2.4 ± 0.2 U/mg protein). These results suggest that a reduction in oxidative stress in diabetic kidney can be achieved with the administration of pioglitazone and to some extent using repaglinide treatment.