Effects of genistein on plasma lipid profiles and vascular function in streptozotocin-induced diabetic rats

Abstract

Diabetes mellitus is associated with increased risks of hypertension, atherosclerosis, and microcirculation disorders. Especially, a number of evidence has suggested that vascular endothelial dysfunction play a major role as underlying cause of a number of diabetic complications. Genistein, the active ingredient of soy product has been suggested for its antioxidant and its endothelial functional improvement. This study determines the treatment effects of genistein on endothelium-dependent and endothelium-independent vasorelaxation of mesenteric arterioles, plasma lipid profiles, blood glucose, and HbA[subscript 1C] level in animal models of diabetes. Male Wistar rats weighing 180-200 g were divided randomly into two major groups of diabetes (DM) and non diabetes (CON). In diabetic group, four subgroups were further randomly divided as follow: 1.) Diabetic groups received 100 microliter of dimethylsulfoxide for 4 and 8 weeks (4-wk DM+DMSO and 8-wk DM+DMSO). 2) Diabetic groups received daily injection of 0.25 mg /kg bw genistein for 4 and 8 weeks (4-wk DM+Gen and 8-wk DM+Gen). On the experimental day, endothelial function of each animal was examined using intravital fluorescent videomicroscopy. FITC-Dx-250 was used as a vascular labeling in mesenteric microcirculation. Image analysis was used to measure arteriolar diameter changes. The results demonstrated that blood glucose level was significantly decreased at both 4 (DM+DMSO = 346.16+-18.39 mg/dl, DM+Gen = 276.50+-20.01 mg/dl; p<0.05) and 8 weeks (DM+DMSO = 465.83+-32.72 mg/dl, DM+Gen = 165.66+-25.46 mg/dl; p<0.05) of genistein administration, whereas HbA[subscript 1C] level was significantly attenuated only at 8 weeks. (DM+DMSO = 10.08+-0.45 %, DM+Gen = 7.71+-0.40 %; p<0.05). However genistein did not have any effects on plasma lipid profiles. In addition, it was found that genistein could prevent diabetes-induced endothelial dysfunction which was characterized by increased response to 10-5 M Ach response in both groups of 4 (DM+DMSO = 6.59+-0.56 %, DM+Gen = 18.48+-1.16 %; p<0.05) and 8 weeks (DM+DMSO = 8.05+-0.41 %, DM+Gen = 14.97+-1.40 %; p<0.05). Conclusion Our findings implied that genistein may protect against damage of both endothelial dependent and independent vasodilation in diabetic rats. Moreover, genistein showed the hypoglycemic effect that might be a direct or indirect action. Therefore, genistein might be used to prevent diabetic cardiovascular complications