Coleman M D., Baker C D.
Mechanisms of Drug Toxicity Group, Pharmaceutical Sciences Institute, Aston University, Aston Triangle, B4 7ET, Birmingham, UK
Environ Toxicol Pharmacol. 2001 Mar;9(4):161-167. doi: 10.1016/s1382-6689(01)00061-8.
The antioxidant effects of dihydrolipoic acid (DHLA) and probucol were investigated in a human erythrocytic in-vitro model of diabetic oxidative stress, where xenobiotics were used to form methaemoglobin. 4-Aminophenol mediated haemoglobin oxidation in non-diabetic erythrocytes was not affected by the presence of either DHLA or probucol. However, with diabetic cells, there were significant increases (P<0.01) in 4-aminophenol-mediated haemoglobin oxidation in the presence of DHLA. Methaemoglobin formed by nitrite in non-diabetic and diabetic cells was not altered by either DHLA or probucol except at one time point in diabetic cells. In non-diabetic as well as diabetic cells, methaemoglobin formed by MADDS-NHOH was significantly reduced at all three time points in the presence of DHLA (P<0.0001) but unaffected by probucol. In the presence of DHLA only, methaemoglobin formed by the products of rat microsomal oxidation of both 4-aminopropiophenone and benzocaine was markedly reduced for both xenobiotics in diabetic and non-diabetic cells (P<0.0001) compared with cells incubated in the absence of DHLA. There were no significant differences between total cellular thiol levels determined between diabetic and non-diabetic erythrocytes, nor did DHLA or probucol affect resting thiol levels. MADDS-NHOH caused a significant thiol depletion in diabetic cells, which was restored in the presence of DHLA. A further study is required to determine how DHLA attenuates the potent REDOX reactions that occur during hydroxylamine-mediated methaemoglobin formation.
在糖尿病氧化应激的人体红细胞体外模型中研究了二氢硫辛酸（DHLA）和普罗布考的抗氧化作用，其中使用外源性物质形成高铁血红蛋白。4-氨基苯酚介导的非糖尿病红细胞中的血红蛋白氧化不受DHLA或普罗布考的影响。然而，对于糖尿病细胞，在存在DHLA的情况下，4-氨基苯酚介导的血红蛋白氧化有显著增加（P<0.01）。除了在糖尿病细胞中的一个时间点外，DHLA或普罗布考均未改变非糖尿病和糖尿病细胞中亚硝酸盐形成的高铁血红蛋白。在非糖尿病和糖尿病细胞中，在存在DHLA的所有三个时间点，MADDS-NHOH形成的高铁血红蛋白均显著降低（P<0.0001），但不受普罗布考的影响。仅在存在DHLA的情况下，与在不存在DHLA的情况下孵育的细胞相比，糖尿病和非糖尿病细胞中4-氨基苯丙酮和苯佐卡因的大鼠微粒体氧化产物形成的高铁血红蛋白均显著降低（P<0.0001）。糖尿病和非糖尿病红细胞之间测定的总细胞巯基水平没有显著差异，DHLA或普罗布考也不影响静息巯基水平。MADDS-NHOH导致糖尿病细胞中的巯基显著耗竭，在存在DHLA的情况下得以恢复。需要进一步研究以确定DHLA如何减弱在羟胺介导的高铁血红蛋白形成过程中发生的强氧化还原反应。
