Mechanisms of Toxicity Group, School of Life and Health Sciences, Aston University, Birmingham B4 7ET, UK.
Environ Toxicol Pharmacol. 2004 May;17(1):55-9. doi: 10.1016/j.etap.2004.01.005.
The respective methaemoglobin forming and GSH depleting capabilities of monoacetyl dapsone hydroxylamine (MADDS-NHOH) and dapsone hydroxylamine (DDS-NHOH) were compared in human diabetic and non-diabetic erythrocytes in vitro with a view to select the most potent agent for future oxidative stress and antioxidant evaluation studies. Administration of both metabolites to non-diabetic erythrocytes over the 20min period of the study resulted in significantly more methaemoglobin formation at all four time points compared with the diabetic erythrocytes (P<0.0001). At all four time points, significantly more methaemoglobin was formed in response to MADDS-NHOH in non-diabetic cells compared with the effects of DDS-NHOH on diabetic erythrocytes (P<0.0001). At the 5 and 10min time points, significantly more methaemglobin was formed in non-diabetic cells in the presence of MADDS-NHOH compared with DDS-NHOH (P<0.05). At the 5min time point only, significantly more methaemoglobin was formed in the presence of MADDS-NHOH in diabetic cells compared with that of DDS-NHOH (P<0.01). However, compared with diabetic control GSH levels, the presence of DDS-NHOH caused a significant depletion in GSH at 5, 10 and 20min time points in diabetic cells (P<0.001). In addition, the presence of DDS-NHOH caused a significant reduction in GSH levels in diabetic cells in comparison with those of non-diabetics at the 5, 10 and 20min, (P<0.005). DDS-NHOH was also associated with a significant depletion of GSH levels in diabetic cells compared with those of non-diabetic control erythrocytes (P<0.0001). The presence of MADDS-NHOH in diabetic erythrocytes led to a significant reduction in GSH levels at the 20min time point compared with those of non-diabetics (P<0.001), but there were no significant differences at the 5, 10 and 15min points. Due to its greater GSH-depleting action, DDS-NHOH will be selected for future use in the oxidative stress assessment in diabetic erythrocytes.
比较了单乙酰对苯二胺羟胺（MADDS-NHOH）和对苯二胺羟胺（DDS-NHOH）在体外对人糖尿病和非糖尿病红细胞的高铁血红蛋白形成和 GSH 耗竭能力，以期选择最有效的药物用于未来的氧化应激和抗氧化评估研究。在研究的 20 分钟期间，两种代谢物均施用于非糖尿病红细胞，与糖尿病红细胞相比，所有四个时间点的高铁血红蛋白形成均明显更多（P<0.0001）。在所有四个时间点，与 DDS-NHOH 对糖尿病红细胞的作用相比，非糖尿病细胞对 MADDS-NHOH 的反应中形成的高铁血红蛋白明显更多（P<0.0001）。在 5 和 10 分钟时间点，非糖尿病细胞中 MADDS-NHOH 的存在下形成的高铁血红蛋白明显多于 DDS-NHOH（P<0.05）。仅在 5 分钟时间点，糖尿病细胞中 MADDS-NHOH 的存在下形成的高铁血红蛋白明显多于 DDS-NHOH（P<0.01）。然而，与糖尿病对照 GSH 水平相比，DDS-NHOH 的存在在 5、10 和 20 分钟时间点导致糖尿病细胞中 GSH 的显著耗竭（P<0.001）。此外，与非糖尿病患者相比，DDS-NHOH 的存在还导致糖尿病细胞中的 GSH 水平在 5、10 和 20 分钟时显著降低（P<0.005）。与非糖尿病对照红细胞相比，DDS-NHOH 在糖尿病细胞中也与 GSH 水平的显著耗竭相关（P<0.0001）。MADDS-NHOH 在糖尿病红细胞中的存在导致与非糖尿病者相比，在 20 分钟时间点 GSH 水平显著降低（P<0.001），但在 5、10 和 15 分钟时无显著差异。由于其更强的 GSH 耗竭作用，DDS-NHOH 将被选择用于未来糖尿病红细胞的氧化应激评估。
