ABSTRACT
Type 2 diabetes (T2D) is associated with increased oxidative stress as indicated by elevated levels of lipid peroxidation and protein oxidation products. Since reactive oxygen species (ROS) can cause damage to biological macromolecules including DNA, this study investigated oxidative damage to DNA using the alkaline (pH > 13) comet assay in peripheral whole blood leukocytes sampled from 15 dyslipidemic T2D patients treated with simvastatin (20 mg/day), 15 dyslipidemic T2D patients not treated with simvastatin, 20 non-dyslipidemic T2D patients, and 20 healthy individuals (controls). Our results showed a greater DNA migration in terms of damage index (DI) (p < 0.01) in the dyslipidemic T2D patients not treated with statin (DI = 67.70 +/- 10.89) when compared to the dyslipidemic T2D patients under statin treatment (DI = 47.56 +/- 7.02), non-dyslipidemic T2D patients (DI = 52.25 +/- 9.14), and controls (DI = 13.20 +/- 6.40). Plasma malondialdehyde (MDA) and C-reactive protein (CRP) levels were also increased and total antioxidant reactivity (TAR) and paraoxonase activity (PON1) decreased in non-dyslipidemic T2D patients and dyslipidemic T2D non-treated with simvastatin. We also found that DI was inversely correlated with TAR (r = -0.61, p < 0.05) and PON1 (r = -0.67, p < 0.01). In addition, there was a significant positive correlation between DI and CRP (r = 0.80, p < 0.01). Our results therefore indicate that simvastatin treatment plays a protective role on oxidative damage to DNA in dyslipidemic T2D patients probably reflecting a general decrease in oxidative stress in these patients.
Subject(s)
Diabetes Mellitus, Type 2/complications , Dyslipidemias/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Leukocytes/drug effects , Oxidative Stress , Simvastatin/therapeutic use , Adult , Aged , Aryldialkylphosphatase/blood , C-Reactive Protein/analysis , Comet Assay , DNA Damage , Dyslipidemias/complications , Female , Humans , Leukocytes/immunology , Leukocytes/metabolism , Male , Malondialdehyde/blood , Middle AgedABSTRACT
BACKGROUND AND AIMS: Oxidative stress is considered an important factor in the development of diabetic complications that causes a variety of changes such as oxidative modification of membrane lipids, nucleic acids and cellular proteins. Dyslipidemia is frequently associated with diabetes and cardiovascular disease. In this context, the objective of this study was to evaluate oxidative modifications of plasma proteins and lipids in non dyslipidemic type 2 diabetic (T2D) patients, in dyslipidemic T2D patients treated or not with simvastatin and in healthy subjects to investigate whether treatment with low doses of simvastatin plays a protective role on the lipid and protein oxidative damage in these patients. METHODS: We determined oxidative damage of plasma proteins by carbonyl assay and total thiol group determination. We also characterized the membrane damage in terms of lipid peroxidation by measuring malonaldehyde (MDA) in nondyslipidemic T2D patients, dyslipidemic T2D patients treated with simvastatin (20 mg/day), dyslipidemic T2D patients not treated with simvastatin and in healthy age-matched control subjects. RESULTS: Our results showed that dyslipidemic T2D patients not treated with simvastatin had significantly higher plasma protein carbonyl groups and MDA when compared to dyslipidemic T2D patients treated with simvastatin and control group. Thiol concentrations from dyslipidemic T2D patients not treated with simvastatin were significantly lower than treated patients and controls. It was verified that the thiols groups were inversely correlated with apolipoprotein B and positively correlated with apolipoprotein A-I. CONCLUSIONS: These results demonstrated that treatment with low doses of simvastatin can minimize the protein and lipid oxidative damage in dyslipidemic T2D patients.
