Noda Y, Mori A, Cossins E, Packer L
Department of Cell and Molecular Biology, University of California, Berkeley 94720-3200, USA.
Metabolism. 2000 Feb;49(2 Suppl 1):14-6. doi: 10.1016/s0026-0495(00)80079-7.
The role of reactive oxygen species in diabetes and its complications are well known. Two therapeutic agents commonly used in the treatment of diabetes are the sulfonylureas gliclazide and glibenclamide. These drugs effectively reduce blood sugar in non-insulin-dependent diabetes mellitus, by augmenting insulin release. Gliclazide is known to be a general free radical scavenger as shown by its inhibition of o-dianisidine photo-oxidation. In this study, the effects of gliclazide and glibenclamide on free radicals were examined in vitro, using electron spin resonance spectroscopy. Superoxide radical (O2*-) generated from the hypoxanthine-xanthine oxidase system or hydroxyl radical (OH*) generated via the Fenton reaction were analyzed as spin adducts of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Gliclazide scavenged O2*- and OH* in a dose-dependent manner whereas glibenclamide was without effect. These findings suggest that gliclazide is not only effective in reducing blood sugar, but may also be beneficial as a result of inhibition of lipid and protein denaturation, which is believed to lead to the development of diabetic complications.
活性氧在糖尿病及其并发症中的作用已广为人知。常用于治疗糖尿病的两种治疗药物是磺脲类药物格列齐特和格列本脲。这些药物通过增加胰岛素释放,有效降低非胰岛素依赖型糖尿病患者的血糖。已知格列齐特是一种一般的自由基清除剂,这一点已通过其对邻联茴香胺光氧化的抑制作用得到证明。在本研究中,使用电子自旋共振光谱法在体外检测了格列齐特和格列本脲对自由基的影响。由次黄嘌呤-黄嘌呤氧化酶系统产生的超氧阴离子自由基(O2*-)或通过芬顿反应产生的羟自由基(OH*)作为5,5-二甲基-1-吡咯啉-N-氧化物(DMPO)的自旋加合物进行分析。格列齐特以剂量依赖的方式清除O2*-和OH*,而格列本脲则无此作用。这些发现表明,格列齐特不仅在降低血糖方面有效,而且由于抑制了脂质和蛋白质变性,可能也是有益的,而脂质和蛋白质变性被认为会导致糖尿病并发症的发生。