Stefek M, Sotnikova R, Okruhlicova L, Volkovova K, Kucharska J, Gajdosik A, Gajdosikova A, Mihalova D, Hozova R, Tribulova N, Gvozdjakova A
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava.
Acta Diabetol. 2000;37(3):111-7. doi: 10.1007/s005920070012.
Consistent with the postulated role of oxidative stress in the etiology of late diabetic complications, pharmacological interventions based on biological antioxidants have been suggested. The aim of the present study was to investigate the effect of dietary supplementation with the pyridoindole antioxidant stobadine on the myocardial antioxidant status and ultrastructure of streptozotocin-diabetic rats. Diabetic male Wistar rats were fed for 32 weeks a standard diet or a diet supplemented with stobadine (0.05% w/w). Control rats received a standard diet or stobadine-supplemented diet (0.16% w/w). Plasma levels of glucose, cholesterol and triglycerides were increased significantly by diabetes. Activities of superoxide dismutase and catalase were markedly elevated in the diabetic myocardium. Myocardial levels of conjugated dienes increased after eight months of diabetes, in spite of significantly increased myocardial alpha-tocopherol and coenzyme Q9 content. The long-term treatment of diabetic animals with stobadine (i) reduced plasma cholesterol and triglyceride levels yet left the severe hyperglycemia unaffected, (ii) reduced oxidative damage of myocardial tissue as measured by conjugated dienes, (iii) reversed myocardial levels of alpha-tocopherol and coenzyme Q9 to near control values, (iv) reduced elevated activity of superoxide dismutase in the diabetic myocardium, and (v) attenuated angiopathic and atherogenic processes in the myocardium as assessed by electron microscopy examination. These results are in accordance with the postulated prooxidant role of chronic hyperglycemia and provide further evidence that development of pathological changes in diabetic myocardium is amenable to pharmacological intervention by biological antioxidants.
与氧化应激在糖尿病晚期并发症病因学中所假定的作用一致，基于生物抗氧化剂的药物干预措施已被提出。本研究的目的是调查膳食补充吡啶并吲哚抗氧化剂司他定对链脲佐菌素诱导的糖尿病大鼠心肌抗氧化状态和超微结构的影响。将雄性糖尿病Wistar大鼠喂食标准饮食或补充司他定（0.05% w/w）的饮食32周。对照大鼠接受标准饮食或补充司他定的饮食（0.16% w/w）。糖尿病显著提高了血浆葡萄糖、胆固醇和甘油三酯水平。糖尿病心肌中超氧化物歧化酶和过氧化氢酶的活性显著升高。糖尿病8个月后，心肌共轭二烯水平升高，尽管心肌α-生育酚和辅酶Q9含量显著增加。用司他定对糖尿病动物进行长期治疗：（i）降低了血浆胆固醇和甘油三酯水平，但严重的高血糖症未受影响；（ii）通过共轭二烯测量，降低了心肌组织的氧化损伤；（iii）使心肌α-生育酚和辅酶Q9水平恢复到接近对照值；（iv）降低了糖尿病心肌中超氧化物歧化酶升高的活性；（v）通过电子显微镜检查评估，减轻了心肌中的血管病变和动脉粥样硬化进程。这些结果与慢性高血糖所假定的促氧化作用一致，并进一步证明糖尿病心肌病理变化的发展可通过生物抗氧化剂进行药物干预。
