Effect of dietary supplementation with the pyridoindole antioxidant stobadine on antioxidant state and ultrastructure of diabetic rat myocardium

Consistent with the postulated role of oxidative stress in the etiology of late diabetic complications, pharmacological interventions based on biologi cal antioxidants have been suggested. The aim of the present study was to i nvestigate the effect of dietary supplementation with the pyridoindole anti oxidant stobadine on the myocardial antioxidant status;and ultrastructure o f streptozotocin-diabetic rats. Diabetic male Wistar rats were fed for 32 w eeks a standard diet or a diet supplemented with stobadine (0.05% w/w). Con trol 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 con jugated dienes increased after eight months of diabetes, in spite of signif icantly increased myocardial alpha -tocopherol and coenzyme Q(9) content. T he long-term treatment of diabetic animals with stobadine (i) reduced plasm a cholesterol and triglyceride levels yet left the severe hyperglycemia una ffected, (ii) reduced oxidative damage of myocardial tissue as measured by conjugated dienes, (iii) reversed myocardial levels of alpha -tocopherol an d coenzyme Q(9) to near control values, (iv) reduced elevated activity of s uperoxide dismutase in the diabetic myocardium, and (v) attenuated angiopat hic and atherogenic processes in the myocardium as assessed by electron mic roscopy examination. These results are in accordance with the postulated pr ooxidant role of chronic hyperglycemia and provide further evidence that de velopment of pathological changes in diabetic myocardium is amenable to pha rmacological intervention by biological antioxidants.