Type 2 diabetes mellitus is associated with elevated level of oxidative stress, which is one of the most important factors responsible for the development of chronic complications of this disease. Moreover, it was shown that diabetic patients had increased level of oxidative DNA damage and decreased effectiveness of DNA repair. These changes may be associated with increased risk of
cancer in T2DM patients, since DNA damage and DNA repair play a pivotal role in malignant transformation. It was found that
gliclazide, an oral
hypoglycemic drug with
antioxidant properties, diminished DNA damage induced by
free radicals. Therefore, the aim of the present study was to evaluate the in vitro impact of
gliclazide on: (i) endogenous basal and oxidative DNA damage, (ii) DNA damage induced by
hydrogen peroxide and (iii) the efficacy of DNA repair of such damage. DNA damage and DNA repair in peripheral blood lymphocytes of 30 T2DM patients and 30 non-diabetic individuals were evaluated by alkaline single cell electrophoresis (comet) assay. The extent of oxidative DNA damage was assessed by
DNA repair enzymes:
endonuclease III and
formamidopyrimidine-DNA glycosylase. The endogenous basal and oxidative DNA damages were higher in lymphocytes of T2DM patients compared to non-diabetic subjects and
gliclazide decreased the level of such damage. The
drug significantly decreased the level of DNA damage induced by
hydrogen peroxide in both groups.
Gliclazide increased the effectiveness of DNA repair in lymphocytes of T2DM patients (93.4% (with
gliclazide) vs 79.9% (without
gliclazide); P< or =0.001) and non-diabetic subjects (95.1% (with
gliclazide) vs 90.5% (without
gliclazide); P< or =0.001). These results suggest that
gliclazide may protect against the oxidative stress-related chronic
diabetes complications, including
cancer, by decreasing the level of DNA damage induced by
reactive oxygen species.