Programa de Pós-Graduação em Ciências Farmacêuticas da Universidade Federal do Rio Grande do Sul, UFRGS, RS, Brazil.
Cell Biochem Funct. 2010 Jul;28(5):360-6. doi: 10.1002/cbf.1654.
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.
2 型糖尿病（T2D）与氧化应激增加有关，表现为脂质过氧化和蛋白质氧化产物水平升高。由于活性氧（ROS）会对包括 DNA 在内的生物大分子造成损伤，因此本研究使用碱性（pH>13）彗星试验检测了外周全血白细胞中的 DNA 氧化损伤，该试验中采集了 15 名接受辛伐他汀（20mg/天）治疗的血脂异常 T2D 患者、15 名未接受辛伐他汀治疗的血脂异常 T2D 患者、20 名非血脂异常 T2D 患者和 20 名健康个体（对照组）的样本。我们的结果显示，未接受他汀类药物治疗的血脂异常 T2D 患者的 DNA 迁移程度更大，损伤指数（DI）更高（p<0.01）（DI=67.70±10.89），与接受他汀类药物治疗的血脂异常 T2D 患者（DI=47.56±7.02）、非血脂异常 T2D 患者（DI=52.25±9.14）和对照组（DI=13.20±6.40）相比。非血脂异常 T2D 患者和未接受辛伐他汀治疗的血脂异常 T2D 患者的血浆丙二醛（MDA）和 C 反应蛋白（CRP）水平也升高，总抗氧化反应性（TAR）和对氧磷酶 1（PON1）活性降低。我们还发现，DI 与 TAR 呈负相关（r=-0.61，p<0.05），与 PON1 呈负相关（r=-0.67，p<0.01）。此外，DI 与 CRP 呈显著正相关（r=0.80，p<0.01）。因此，我们的结果表明，辛伐他汀治疗在血脂异常的 T2D 患者中对 DNA 氧化损伤起保护作用，这可能反映了这些患者氧化应激的普遍降低。
