大剂量维生素E和C抗氧化活性及对DNA损伤影响的研究

Effect of High Dose Vitamin E and C on Antioxidative Activity and DNA Damage in Rats

背景与目的:观察大剂量维生素E(VitaminE,VE)和C(VitaminC,VC)的抗氧化活性及对大鼠DNA氧化损伤、烷化损伤的影响。材料与方法:将72只Wistar大鼠(雌雄各半)随机分为6组,每组12只,即对照组(基础饲料,VE、VC摄入量分别为5、0mg/kg·d),VC组(VE5mg/kg·d、VC1000mg/kg·d),VE1组(VE33mg/kg·d、VC0mg/kg·d),VE2组(VE500mg/kg·d、VC0mg/kg·d),VE1+VC组(VE33mg/kg·d、VC1000mg/kg·d)和VE2+VC组(VE500mg/kg·d、VC1000mg/kg·d),实验期为8周。实验结束前收集动物24h尿液,实验结束后处死动物,留取血液,分离血浆并收集淋巴细胞,测定超氧化物歧化酶(Superoxidedismutase,SOD)、谷胱甘肽过氧化物酶(Glutathioneperoxidase,GSH-Px)活性、丙二醛(Malondialdehyde,MDA)含量,分析DNA损伤。结果:VE1组的抗氧化活性显著提高:血浆SOD、GSH-Px活力明显高于对照组(P<0.05)、MDA含量低于对照组;而VE1+VC组SOD、GSH-Px则较VE1组显著下降(P<0.05)。VE1组10μmol/LH2O2诱导的淋巴细胞DNA氧化损伤为150.42AU,显著低于其它组(P<0.05);该组DNA烷化损伤产物尿O6-甲基鸟嘌呤(O6-methylguanine,O-6meG)含量为0.89mg/g肌酐,比对照组、VE2组分别下降了50.28%、50.00%(P<0.05)。结论:较大剂量VE能提高大鼠抗氧化活性,降低DNA氧化损伤及烷化损伤,但联合补充大剂量VC时可能对其影响产生拮抗作用;过大剂量VE和VC补充时均未观察到有利作用,并且可能降低机体的遗传稳定性。

BACKGROUND ＆ AIM： To investigate the antioxidative activity of high doses vitamin E（VE） and C（Vc） and its effects on DNA oxidative and alkyl damages in rats. MATERIAL AND METHODS： 72 Wistar rats were randomly divided into six groups including control,Vc,VE1,VE2, VE1＋Vc and VE2＋Vc groups. The trial lasted 8 weeks,and urine and blood samples of each rat were collected at the end of the trial. The activities of superoxide dismutase （SOD）,glutathione peroxidase （GSH-Px）, level of malondialdehyde （MDA） and DNA damage were assessed. RESULTS： Plasma SOD and GSH-Px activities in VE1 group were 425.21 NU/ml and 440.08 U/ml, respectively which were significantly higher than those of the control group while MDA in this group was significantly lower than that of the control. The same antioxidative enzyme activities in VE1 ＋ Vc group were significantly lower than that of the VE1 group. Lymphocyte DNA oxidative damage induced by 10 μmol/L H2O2 in VE1 group was significantly lower than those in other groups and O-^6 methyl guanine （O-^6 meG） level in this group was 0.89 mg/g creatinine which was significantly lowered by 50.28%,50.00% compared with that of control group and that of the VE2 group, respectively. CONCLUSION： Relatively high dose VE could effectively increase antioxidative activity and decrease DNA oxidative and alkyl damages. Using the same dose of VE and Vc supplements in combination was found to confer no such advantageous effect. Too high dose VE and Vc could decrease the genetic stability.