Department of Biochemistry and Molecular Biology, Aging and Apoptosis Research Center, Seoul National University College of Medicine, Seoul 110-799, South Korea.
Free Radic Res. 2010 Aug;44(8):871-80. doi: 10.3109/10715762.2010.486831.
The antibiotic drug 4,4'-diaminodiphenylsulphone (DDS) is used to treat several dermatologic diseases, including Hansen's disease. This study confirmed the antioxidant nature of DDS in hydrogen peroxide (H(2)O(2))-induced oxidative stress and assessed its role in other apoptotic stresses in human diploid fibroblasts (HDFs). Oxidative stress was effectively reduced by DDS in a dose-dependent manner. Moreover, the oxidative stress-induced increases in the levels of the p53 and p21 proteins were inhibited by pre-treatment with DDS. In addition, H(2)O(2) and DDS increased the level of cytochrome P450 (CYP450) IIE1 in HDFs, implicating a role for DDS in H(2)O(2) scavenging via the activation of CYP450. DDS treatment increased the activity of catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR), as well as the GSH/GSSG ratio, indicating activation of the glutathione system against oxidative stress. However, DDS showed no protective effects on HDFs against other apoptotic stimuli, such as thapsigargin and staurosporine, suggesting that DDS would act only against oxidative stress. Therefore, in addition to its antibiotic function, DDS is a potent antioxidant against H(2)O(2)-induced oxidative stress in HDFs.
抗生素药物 4,4'-二氨基二苯砜（DDS）用于治疗多种皮肤疾病，包括麻风病。本研究证实了 DDS 在过氧化氢（H₂O₂）诱导的氧化应激中的抗氧化性质，并评估了其在人二倍体成纤维细胞（HDF）中其他凋亡应激中的作用。DDS 以剂量依赖的方式有效降低了氧化应激。此外，DDS 预处理抑制了氧化应激诱导的 p53 和 p21 蛋白水平的增加。此外，H₂O₂和 DDS 增加了 HDF 中细胞色素 P450（CYP450）IIE1 的水平，表明 DDS 通过激活 CYP450 在 H₂O₂清除中起作用。DDS 处理增加了过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GPx）和谷胱甘肽还原酶（GR）的活性，以及 GSH/GSSG 比值，表明谷胱甘肽系统对氧化应激的激活。然而，DDS 对 HDF 对其他凋亡刺激物（如他普西龙和星形孢菌素）没有保护作用，表明 DDS 仅对氧化应激起作用。因此，除了其抗生素功能外，DDS 还是一种有效的抗氧化剂，可对抗 HDF 中的 H₂O₂诱导的氧化应激。
