Simvastatin treatment prevents oxidative damage to DNA in whole blood leukocytes of dyslipidemic type 2 diabetic patients.
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.
Manfredini
Vanusa
V
Programa de Pós-Graduação em Ciências Farmacêuticas da Universidade Federal do Rio Grande do Sul, UFRGS, RS, Brazil.
Biancini
Giovana Brondani
GB
Vanzin
Camila Simioni
CS
Dal Vesco
Anna Maria Ribeiro
AM
Cipriani
Franciele
F
Biasi
Lidiana
L
Treméa
Roberta
R
Deon
Marion
M
Peralba
Maria do Carmo Ruaro
Mdo C
Wajner
Moacir
M
Vargas
Carmen Regla
CR
D000328:Adult; D000368:Aged; D043303:Aryldialkylphosphatase / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D020552:Comet Assay; D004249:DNA Damage; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D050171:Dyslipidemias / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007962:Leukocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D018384:Oxidative Stress; D019821:Simvastatin / Q000627:therapeutic use*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008315:Malondialdehyde; D002097:C-Reactive Protein; D019821:Simvastatin; D043303:Aryldialkylphosphatase