Coleman Michael D, Rimmer Georgina S E, Haenen Guido R M M
School of Life and Health Sciences, Aston University, Birmingham, UK.
Basic Clin Pharmacol Toxicol. 2007 Feb;100(2):139-44. doi: 10.1111/j.1742-7843.2006.00025.x.
The effects of lipoic acid and dihydrolipoic acid were explored on total thiol maintenance in diabetic and non-diabetic human erythrocytes in vitro over 22 hr in a 37 degrees C incubation system with no added glucose. Over 18-22.5 hr after treatment in both non-diabetic and diabetic cells, lipoic acid (1 mM) was associated with greater loss of cellular thiols than dihydrolipoic acid (1 mM), compared to respective control values. At 0.1 mM, in non-diabetic cells, although lipoic acid-treated cells' thiol levels were significantly lower than control, there was no significant difference between dihydrolipoic acid-treated cells and control cells regarding thiol levels. In addition, at 0.1 mM, dihydrolipoic acid-treated diabetic cells showed a reduction in thiol levels compared to control. At 0.01 mM, lipoic acid-treated cells had significantly lower measured thiol levels compared with diabetic cells exposed to dihydrolipoic acid, whereas in non-diabetic cells, dihydrolipoic acid-treated erythrocytic thiol levels were significantly greater than those treated with lipoic acid, although there were no other significant differences between the groups. At 22.5 hr, control values of methaemoglobin rose to 6.4 +/- 1.1% in diabetic cells and 3.6 +/- 2.1% in non-diabetic cells. Lipoic acid (1 mM) showed greater methaemoglobin formation in diabetic rather than non-diabetic cells (13.6 +/- 1.5% versus 11.6 +/- 1.5%), whereas dihydrolipoic acid-treated diabetic and non-diabetic cells were less potent in methaemoglobin generation (8.5 +/- 2.4% and 8.4 +/- 1.4%, respectively). These studies suggest that in certain circumstances such as hypoglycaemia, lipoic acid administration may actually be detrimental to cellular oxidant protection status.
在无添加葡萄糖的37℃孵育系统中，对糖尿病和非糖尿病患者的人红细胞进行体外22小时实验，探究硫辛酸和二氢硫辛酸对总硫醇维持的影响。在非糖尿病和糖尿病细胞中处理18 - 22.5小时后，与各自的对照值相比，硫辛酸（1 mM）导致细胞硫醇的损失比二氢硫辛酸（1 mM）更大。在非糖尿病细胞中，0.1 mM时，虽然硫辛酸处理的细胞硫醇水平显著低于对照，但二氢硫辛酸处理的细胞与对照细胞在硫醇水平上没有显著差异。此外，在0.1 mM时，二氢硫辛酸处理的糖尿病细胞与对照相比硫醇水平降低。在0.01 mM时，硫辛酸处理的细胞测量硫醇水平显著低于暴露于二氢硫辛酸的糖尿病细胞，而在非糖尿病细胞中，二氢硫辛酸处理的红细胞硫醇水平显著高于硫辛酸处理的细胞，尽管各组之间没有其他显著差异。在22.5小时时，糖尿病细胞中高铁血红蛋白的对照值升至6.4±1.1%，非糖尿病细胞中升至3.6±2.1%。硫辛酸（1 mM）在糖尿病细胞中比在非糖尿病细胞中显示出更高的高铁血红蛋白形成（13.6±1.5%对11.6±1.5%），而二氢硫辛酸处理的糖尿病和非糖尿病细胞在高铁血红蛋白生成方面作用较小（分别为8.5±2.4%和8.4±1.4%）。这些研究表明，在某些情况下，如低血糖，给予硫辛酸实际上可能对细胞抗氧化保护状态有害。
