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

Abstract

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.

Ultrastructure and histochemistry of rat myocardial capillary endothelial cells in response to diabetes and hypertension

“…Histochemical techniques used in our previous studies have shown heterogeneously reduced activities of some other enzymes involved in metabolic and energetic processes in the heart of diabetic and hypertensive rats [8,11,30] that may contribute to its dysfunction. In addition to enzyme histochemistry, our studies demonstrated that capillary endothelial cells revealed similar reversible and irreversible subcellular alterations in the myocardium of diabetic and hypertensive animals [8,11,30,37] manifested by thickening of basal membrane, diminished number of ribosomes and pinocytic vesicles, injured mitochondria and electrolucent nuclear chromatin, various density of cytoplasm together with endothelial cell swelling accompanied by luminal narrowing, diversity of capillary calibre, endothelial extravastion, branching of capillaries and pericapillary fibrosis. They represent structural form of endothelial dysfunction and seem to make up an integral part of degradation processes in capillaries and might contribute to accelerated disappearance of capillary endothelium.…”

Ischemia-reperfusion injury of the isolated diabetic rat heart: effect of the antioxidant stobadine

“…Yet these substances failed to improve the functional recovery after ischemia/reperfusion. The anti-dysrhythmic properties of STB may be mediated by its potent antioxidant protective effect, already shown in previous studies (Stasko et al 1990;Stefek et al 2000;Kucharska et al 2000), while the HR-lowering effect seems also to be involved. Additional studies are to determine which other potential mechanisms of action come into play.…”

“…STB also prevented degenerative changes seen in diabetic sympathetic nerves of the vas deferens (Gunes et al 2005) and significantly reduced oxidative damage of kidney tissue as well as diabetes-induced proteinuria and albuminuria (Stefek et al 2002). Long-term treatment of diabetic animals with STB attenuated pathological changes in the diabetic myocardium by diminishing oxidative damage of myocardial tissue and reducing angiopathic and atherogenic processes in the myocardium Stefek et al 2000). These findings, along with the high oral bioavailability of STB, its toxic safety, as well as efficient detoxification pathways, render this drug a prospective agent in the prevention of late diabetic complications (for review see Juranek et al 2010).…”

PAMAM dendrimers — diverse biomedical applications. Facts and unresolved questions

“…In Wistar nondiabetic rats CoQ 10 is known to comprise 10-16% of the total amount of mitochondrial CoQ, while in diabetic rats this ratio is between 8-12%. However, the content of CoQ forms has been reported to significantly increase in diabetic rats (up to 2.5 fold) [75,76]. Treatment with PAMAM G4 suppressed the concentration of these antioxidants, typically elevated in diabetic rats, to levels relevant to non-diabetic animals [76]; which may be regarded as indicative that PAMAM G4 had the ability to suppress oxidative stress in experimental diabetes rats.…”

“…However, the content of CoQ forms has been reported to significantly increase in diabetic rats (up to 2.5 fold) [75,76]. Treatment with PAMAM G4 suppressed the concentration of these antioxidants, typically elevated in diabetic rats, to levels relevant to non-diabetic animals [76]; which may be regarded as indicative that PAMAM G4 had the ability to suppress oxidative stress in experimental diabetes rats. The increased antioxidant activity is likely triggered by persistent hyperglycaemic states as a response to oxidative stress in diabetes [33,72,73,75,76], while it normalizes when high glucose, and the associated postsynthetic modifications of proteins, become ameliorated with the administration of PAMAM G4.…”