Coleman MD, Walker CL
Mechanisms of Drug Toxicity Group, Pharmaceutical Sciences Institute, Aston University, Aston Triangle, B4 7ET, Birmingham, UK
Environ Toxicol Pharmacol. 2000 Jan 1;8(2):127-132. doi: 10.1016/s1382-6689(00)00034-x.
The effects of oxidised alpha-lipoic acid and alpha-tocopherol were investigated on a human erythrocytic in vitro model of diabetic metabolic stress. Preincubation of non-diabetic and diabetic erythrocytes with oxidised alpha-lipoic acid or alpha-tocopherol resulted in marked increases in nitrite-mediated methaemoglobin formation. In contrast, oxidised alpha-lipoic acid resulted in considerable reductions in 4-aminophenol-mediated methaemoglobin formation in both diabetic and non-diabetic cells. alpha-Tocopherol showed an increase only in diabetic cells, at one time point. Monoacetyl dapsone hydroxylamine (MADDS-NHOH)-mediated methaemoglobin formation was reduced by oxidised alpha-lipoic acid in non-diabetic and diabetic cells at all three time points, although alpha-tocopherol had no effect with MADDS-NHOH. In diabetic cells only, alpha-tocopherol incubation caused a reduction in GSH levels compared with non-diabetic cells. As the agents showed pro- as well as anti-oxidant effects in this study, further studies are required to demonstrate potential diabetic benefit from alpha-lipoic acid adminstration.
在糖尿病代谢应激的人红细胞体外模型上研究了氧化型α-硫辛酸和α-生育酚的作用。用氧化型α-硫辛酸或α-生育酚对非糖尿病和糖尿病红细胞进行预孵育,导致亚硝酸盐介导的高铁血红蛋白形成显著增加。相比之下,氧化型α-硫辛酸导致糖尿病和非糖尿病细胞中4-氨基苯酚介导的高铁血红蛋白形成大幅减少。α-生育酚仅在一个时间点使糖尿病细胞中的高铁血红蛋白形成增加。在所有三个时间点,氧化型α-硫辛酸均使非糖尿病和糖尿病细胞中由单乙酰氨苯砜羟胺(MADDS-NHOH)介导的高铁血红蛋白形成减少,而α-生育酚对MADDS-NHOH无影响。仅在糖尿病细胞中,与非糖尿病细胞相比,α-生育酚孵育导致谷胱甘肽水平降低。由于本研究中这些试剂显示出促氧化和抗氧化作用,因此需要进一步研究以证明α-硫辛酸给药对糖尿病的潜在益处。