Assessment of DNA base oxidation and glutathione level in patients with type 2 diabetes

Abstract

The first aim of the present study was to examine the relationship between reduced glutathione (GSH) level, a powerful cellular antioxidant, and oxidative damage to DNA; and secondly, to see the effect of glycemic control on oxidative DNA damage in type 2 diabetics. We determined GSH level and, using the comet assay, formamidopyrimidine DNA glycosylase (Fpg)-sensitive sites which indicates oxidised guanine in freshly isolated blood from age-matched type 2 diabetics and controls. We found significant differences between men and women in the control group for both GSH and Fpg-sensitive sites. Therefore, we compared the controls and type 2 diabetics separately in men and women. GSH level of whole blood was found to be lower, Fpg-sensitive sites in leukocytes was found to be higher in the both type 2 diabetic men and women, as compared with their respective controls. When the diabetic group was divided into two groups as well-controlled diabetics and poorly-controlled diabetics with respect to glycosylated haemoglobine levels, it was found that Fpg-sensitive sites was significantly higher in the poorly-controlled diabetics than in the well-controlled diabetics in both the men and women. GSH level was lower in the poorly-controlled diabetics but not significantly. Fpg-sensitive sites were found to be moderately correlated with both glycosylated haemoglobine and GSH, and weakly correlated with glucose. Data indicate that decreased GSH level may be a contributory factor for enhanced oxidative DNA damage in type 2 diabetics; and chronic hyperglycemia derived from poorly-controlled diabetic conditions may induce oxidative DNA damage in these patients. (C) 2002 Elsevier Science B.V. All rights reserved.