Coleman Michael D, Fernandes Sandra, Khanderia Leena
Mechanisms of Drug Toxicity Group, Department of Pharmaceutical Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK.
Environ Toxicol Pharmacol. 2003 Jun;14(1-2):69-75. doi: 10.1016/S1382-6689(03)00027-9.
Eight otherwise healthy diabetic volunteers took a daily antioxidant supplement consisting of vitamin E (200 IU), vitamin C (250 mg) and α-lipoic acid (90 mg) for a period of 6 weeks. Diabetic dapsone hydroxylamine-mediated methaemoglobin formation and resistance to erythrocytic thiol depletion was compared with age and sex-matched non-diabetic subjects. At time zero, methaemoglobin formation in the non-diabetic subjects was greater at all four time points compared with that of the diabetic subjects. Resistance to glutathione depletion was initially greater in non-diabetic compared with diabetic samples. Half-way through the study (3 weeks), there were no differences between the two groups in methaemoglobin formation and thiol depletion in the diabetic samples was now lower than the non-diabetic samples at 10 and 20 min. At 6 weeks, diabetic erythrocytic thiol levels remained greater than those of non-diabetics. HbA(1c) values were significantly reduced in the diabetic subjects at 6 weeks compared with time zero values. At 10 weeks, 4 weeks after the end of supplementation, the diabetic HbA1(c) values significantly increased to the point where they were not significantly different from the time zero values. Total antioxidant status measurement (TAS) indicated that diabetic plasma antioxidant capacity was significantly improved during antioxidant supplementation. Conversion of α-lipoic acid to dihydrolipoic acid (DHLA) in vivo led to potent interference in a standard fructosamine assay kit, negating its use in this study. This report suggests that triple antioxidant therapy in diabetic volunteers attenuates the in vitro experimental oxidative stress of methaemoglobin formation and reduces haemoglobin glycation in vivo.
八名其他方面健康的糖尿病志愿者连续6周每日服用一种抗氧化补充剂，该补充剂包含维生素E（200国际单位）、维生素C（250毫克）和α-硫辛酸（90毫克）。将糖尿病患者经氨苯砜羟胺介导的高铁血红蛋白形成及对红细胞巯基耗竭的抵抗力与年龄和性别匹配的非糖尿病受试者进行比较。在时间零点，与糖尿病受试者相比，非糖尿病受试者在所有四个时间点的高铁血红蛋白形成均更多。与糖尿病样本相比，非糖尿病样本最初对谷胱甘肽耗竭的抵抗力更强。在研究进行到一半（3周）时，两组在高铁血红蛋白形成方面没有差异，并且糖尿病样本在10分钟和20分钟时的巯基耗竭现在低于非糖尿病样本。在6周时，糖尿病患者的红细胞巯基水平仍高于非糖尿病患者。与时间零点的值相比，糖尿病受试者在6周时的糖化血红蛋白（HbA1c）值显著降低。在10周时，即补充结束4周后，糖尿病患者的HbA1c值显著升高至与时间零点的值无显著差异的水平。总抗氧化状态测量（TAS）表明，在抗氧化补充期间，糖尿病患者血浆抗氧化能力显著提高。α-硫辛酸在体内转化为二氢硫辛酸（DHLA）会对标准果糖胺检测试剂盒产生强烈干扰，因此本研究未使用该试剂盒。本报告表明，对糖尿病志愿者进行三联抗氧化治疗可减轻体外实验中高铁血红蛋白形成的氧化应激，并降低体内血红蛋白糖化。
