Cumaoglu Ahmet, Cevik Cemal, Rackova Lucia, Ari Nuray, Karasu Cimen
Department of Medical Biochemistry, Faculty of Medicine, Gazi University, Ankara, Turkey.
Biofactors. 2007;30(3):171-8. doi: 10.1002/biof.5520300304.
Increased oxidative/nitrosative stress is important in the pathogenesis of diabetic complications, and the protective effects of antioxidants are a topic of intense research. The purpose of this study was to investigate whether a pyridoindole antioxidant stobadine (STB) have a protective effect on tissue oxidative protein damage represented by the parameters such as protein carbonylation (PC), protein thiol (P-SH), total thiol (T-SH) and non-protein thiol (Np-SH), nitrotyrosine (3-NT), and advanced oxidation protein products (AOPP) in streptozotocin-diabetic rats.
Diabetes was induced in male Wistar rats by intraperitonal injection of streptozotocin (55 mg/kg). Some of the non-diabetic (control) and diabetic rats treated with STB (24.7 mg/kg/day) during 16 weeks, and the effects on blood glucose, PC, AOPP, 3-NT, P-SH, T-SH and Np-SH were studied. Biomarkers were assayed by enzyme-linked immunosorbent assay (ELISA) or by colorimetric methods.
Administration of stobadine to diabetic animals lowered elevated blood glucose levels by approximately 16% relative to untreated diabetic rats. Although stobadine decreased blood glucose, poor glycemic control was maintained in stobadine treated diabetic rats during the treatment period. Biochemical analyses of liver proteins showed significant diminution of sulfhydryl groups, P-SH, T-SH, Np-SH, and elevation of carbonyl groups in diabetic animals in comparison to healthy controls. As a biomarker of nitrosative stress, 3-NT levels did not significantly change by diabetes induction or by stobadine treatment when compared to control animals. However, the treatment with stobadine resulted in a significant decrease in PC, AOPP levels and normalized P-SH, T-SH, Np-SH groups in liver of diabetic animals.
The results are in accordance with the pro-oxidant role of chronic hyperglycemia, and the ability of stobadine to attenuate protein oxidation and improving tissue reductive capacity may account, at least partly for its observed beneficial effects on tissue function in diabetes.
氧化/亚硝化应激增加在糖尿病并发症的发病机制中起重要作用，抗氧化剂的保护作用是一个深入研究的课题。本研究的目的是探讨吡啶吲哚抗氧化剂司他丁（STB）是否对链脲佐菌素诱导的糖尿病大鼠中以蛋白质羰基化（PC）、蛋白质巯基（P-SH）、总巯基（T-SH）和非蛋白质巯基（Np-SH）、硝基酪氨酸（3-NT）以及晚期氧化蛋白产物（AOPP）等参数所代表的组织氧化蛋白损伤具有保护作用。
通过腹腔注射链脲佐菌素（55mg/kg）诱导雄性Wistar大鼠患糖尿病。部分非糖尿病（对照）大鼠和糖尿病大鼠在16周内接受司他丁（24.7mg/kg/天）治疗，研究其对血糖、PC、AOPP、3-NT、P-SH、T-SH和Np-SH的影响。生物标志物通过酶联免疫吸附测定（ELISA）或比色法进行检测。
给糖尿病动物施用司他丁后，相对于未治疗的糖尿病大鼠，血糖水平降低了约16%。尽管司他丁降低了血糖，但在治疗期间，接受司他丁治疗的糖尿病大鼠血糖控制仍较差。与健康对照相比，糖尿病动物肝脏蛋白质的生化分析显示巯基、P-SH、T-SH、Np-SH显著减少，羰基增加。作为亚硝化应激的生物标志物，与对照动物相比，糖尿病诱导或司他丁治疗后3-NT水平未显著变化。然而，司他丁治疗导致糖尿病动物肝脏中PC、AOPP水平显著降低，P-SH、T-SH、Np-SH组恢复正常。
结果符合慢性高血糖的促氧化作用，司他丁减轻蛋白质氧化和提高组织还原能力的能力可能至少部分解释了其对糖尿病组织功能观察到的有益作用。
